Gray matter microstructural abnormalities in temporal lobe epilepsy with hippocampal sclerosis and MRI negative

Objective

To assess the changes of cortical microstructure in patients with temporal lobe epilepsy combined with hippocampal sclerosis (TLE-HS) and MRI-negative TLE (negative-TLE) and its correlation with clinical characteristics.

Methods

A total of 59 TLE-HS patients, 47 negative-TLE patients, and 67 healthy controls (HC) participated in this study. Gray matter-based spatial statistics (GBSS) analysis was performed using neurite orientation dispersion and density imaging (NODDI) data to compare differences in gray matter (GM) microstructure across the groups, including neurite density index (NDI), orientation dispersion index (ODI). Microstructural indicators were determined to be statistically significant using the threshold-free cluster enhancement method, and multiple comparisons were corrected using the family-wise error (FWE) method. P_FWE < 0.05 was considered statistically significant. The correlation between the indicator values of significantly different brain regions and clinical characteristics was also analyzed.

Results

Compared with the HC group, TLE-HS exhibited widespread reductions in NDI and ODI values within GM, and these changes were primarily affecting the bilateral frontotemporal lobes and limbic system. In contrast to the negative-TLE group, the decrease in NDI in TLE-HS patients was more localized and showed partial lateralization. This decrease was most pronounced in the bilateral frontal pole, frontal gyrus, left temporal pole, temporal gyrus, parahippocampal gyrus, insula, precuneus, cingulate gyrus, and anterior and posterior central gyrus. The NDI values in several gray matter regions in TLE patients were positively correlated with disease onset age, with moderate positive correlations predominantly observed in the middle frontal gyrus, temporal pole, and parahippocampal gyrus. Additionally, NDI values in the parahippocampal gyrus were negatively correlated with disease duration.

Conclusion

TLE-HS patients show extensive GM microstructural changes, primarily in the frontotemporal lobe and limbic system. Our findings support the hypothesis that TLE-HS and MRI-negative TLE represent two distinct pathological entities. This study provides strong evidence of the pattern of microstructural alterations in TLE and offers insights into the understanding of GM microstructural changes in TLE patients.