To explore the potential mechanisms of cognitive impairment in children with MRI-negative pharmacoresistant epilepsy due to focal cortical dysplasia: A pilot study from gray matter structure view

Abstract

Objectives: To investigate the characteristics of brain structure in children with focal cortical dysplasia (FCD)-induced pharmacoresistant epilepsy, and explore the potential mechanisms of cognitive impairment from the view of gray matter alteration.

Methods: 25 pharmacoresistant pediatric patients with pathologically confirmed focal cortical dysplasia (FCD), and 25 gender-matched healthy controls were included in this study. 3.0T MRI data and intelligence tests using the Wechsler Intelligence Scale for Children-Forth Edition (WISC-IV) were generated for all subjects. Voxel-based morphometry (VBM)-diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) and surface-based morphometry (SBM) analyses were performed to analyze gray matter volume and cortical structure. Two-sample t-tests were used to compare the differences in gray matter volume (P＜0.05, FWE) and cortical thickness (P＜0.001, FWE) between the two groups. Also, the Spearman rank correlation analyses were employed to determine the relationship between structural alterations and neuropsychological results.

Results: The WISC-IV scores of the FCD group were significantly lower than those of the HC group in terms of full-scale intelligence quotient (FSIQ), verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), and processing speed index (PSI) (all P＜0.01). Compared with the HC group, in the FCD group, the gray matter volume (GMV) reduced significantly in the left cerebellum_8, cerebellum_Crus2, and bilateral thalamus (P＜0.05, FWE); the GMV increased in the bilateral medial frontal gyrus, right precuneus, and left inferior temporal gyrus (P＜0.05, FWE), and the cortical thickness increased in the bilateral frontal, parietal, and temporal areas (P＜0.001, FWE). Correlation analyses showed that the age of seizure onset had positive correlations with the WISC-IV scores significantly. Meanwhile, the cortex thicknesses of the left pars opercularis gyrus, left middle temporal gyrus, and right inferior temporal gyrus had negative correlations with the WISC-IV scores significantly.

Conclusion: FCD patients showed subtle structural abnormalities in multiple brain regions, with significant involvement of the primary visual cortex and language function cortex. And we also demonstrated a crucial correlation between gray matter structural alteration and cognitive impairment.

Keywords: Cognitive function; Focal cortical dysplasia; Magnetic resonance imaging; Pharmacoresistant epilepsy; Structural abnormalities.

Fig. 1

Box plots of raw data for control and epilepsy patient groups' Wechsler Intelligence Scale for Children-Forth Edition (WISC-IV) score. Data are median (central line), interquartile range (box margins), adjacent values (whiskers), and outliers (dots).

Fig. 2

The difference of gray matter volume between FCD and HCs (P < 0.05, FWE corrected). Representative views are shown with a color-coded depiction of abnormalities. Regions of reduced volume are shown in blue to yellow and regions of increased volume are shown in yellow to red (color-coded according to z value). FCD, focal cortical dysplasia; HCs, healthy controls; FWE, family-wise error. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 3

Regions of increased cortical thickness between FCD and HCs (P < 0.001, FWE corrected) represent views with a color-coded depiction of abnormalities. Regions of increased volume are shown in yellow to red (color-coded according to p-value). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)

Fig. 4

Scatter plots of FSIQ, VCI, PRI, WMI, PSI positively correlated with the age of seizure onset in FCD patients.

Fig. 5

Scatter plots of the mean cortical thickness in the left pars opercularis, the left middle temporal, the right inferior temporal gyrus negatively correlated with WISC-IV scores in FCD patients.

Fig. 6

Spearman's rank correlation matrix between brain regions and WISC-IV scores in FCD patients (adjusted P < 0.05).