Altered Structural Network in Newly Onset Childhood Absence Epilepsy

Abstract

Background and purpose: Recent quantitative neuroimaging studies of childhood absence epilepsy (CAE) have identified various structural abnormalities that might be involved in the onset of absence seizure and associated cognitive and behavioral functions. However, the neuroanatomical alterations specific to CAE remain unclear, and so this study investigated the regional alterations of brain structures associated with newly diagnosed CAE.

Methods: Surface and volumetric magnetic resonance imaging data of patients with newly diagnosed CAE (n=18) and age-matched healthy controls (n=18) were analyzed using Free-Surfer software. A group comparison using analysis of covariance was performed with significance criteria of p<0.05 and p<0.01 in global and regional analyses, respectively.

Results: Compared with control subjects, the patients with CAE had smaller total and regional volumes of cortical gray-matter (GM) in the right rostral middle frontal, right lateral orbitofrontal, and left rostral middle frontal regions, as well as in the right precentral, right superior, middle, left middle, and inferior temporal gyri. The cortex in the right posterior cingulate gyrus and left medial occipital region was significantly thicker in patients with CAE than in controls.

Conclusions: Patients with CAE showed a reduced bilateral frontotemporal cortical GM volume and an increased posterior medial cortical thickness, which are associated with the default mode network. These structural changes can be suggested as the neural basis of the absence seizures and neuropsychiatric comorbidities in CAE.

Keywords: absence epilepsy; cerebral cortex; gray matter; magnetic resonance imaging.

Fig. 1. Comparison of the volumes of brain between patients with CAE and controls. Scatter plots and trend lines of the mean volumes of the (A) total brain, (B) total GM, (C) total WM, (D) cortical GM, and (E) subcortical GM according to age in magnetic resonance imaging evaluations of patients with CAE and control subjects. Both groups show age-related increases in total brain and WM volumes, and age-related reductions in total, cortical, and subcortical GM volumes. (D) The patients with CAE showed a significantly smaller total cortical GM volume compared with control subjects (p=0.042). CAE: childhood absence epilepsy, GM: gray-matter, WM: white-matter.

Fig. 2. Illustration of regional differences in cortical GM volumes between patients with CAE and healthy control subjects (p<0.01). A: The regions with decreased cortical GM volumes relative to those in the controls in the patients with CAE are shown in blue (color coding reflects t values). B: The cortical GM volumes in the right rostral middle frontal; lateral orbitofrontal; precentral, superior, and middle temporal; and left rostral middle frontal, supramarginal, middle, and inferior temporal gyri were smaller in the patients with CAE than in the controls. Comparisons of cortical volumes (in cubic millimeters) are presented as box plots. Each box plot shows the median (50th percentile; dark bar), values to the 1.5 interquartile range (whiskers) and 25th percentile to 75th percentile range (box). CAE: childhood absence epilepsy, GM: gray-matter.

Fig. 3. Scatter plots and trend lines of the mean cortical thickness according to age in magnetic resonance imaging evaluations of patients with CAE and control subjects. Both groups show age-related cortical thinning. However, there was no significant difference between the patients with CAE and the controls in the comparison of the mean cortical thickness of (A) the right and (B) left hemisphere. CAE: childhood absence epilepsy.

Fig. 4. Regional differences in cortical thickness between patients with CAE and healthy control subjects (p<0.01). A: Regions with thicker cortices are shown in red to yellow (color coding reflects t values). B: The right posterior cingulated and left medial occipital gyri are significantly thicker in patients with CAE than in the controls. Comparisons of cortical thicknesses (in millimeters) are presented as box plots. Each box plot shows the median (50th percentile; dark bar), values to the 1.5 interquartile range (whiskers) and 25th percentile to 75th percentile range (box). CAE: childhood absence epilepsy.