Dataset Information

Cortical and subcortical volume differences between Benign Epilepsy with Centrotemporal Spikes and Childhood Absence Epilepsy.

ABSTRACT:

Objective

Benign Childhood Epilepsy with Centrotemporal Spikes (BECTS) and Childhood Absence Epilepsy (CAE) are the most common childhood epilepsy syndromes and they share a similar age-dependence. However, the two syndromes clearly differ in seizures and EEG patterns. The aim of this study is to investigate whether children of the same age with BECTS, CAE and typically-developing children have significant differences in grey matter volume that may underlie the different profiles of these syndromes.

Methods

Twenty one patients with newly-diagnosed BECTS and 18 newly diagnosed and drug naïve CAE were included and compared to 31 typically-developing children. Voxel-based morphometry was utilized to investigate grey matter volume differences among BECTS, CAE, and controls. We also examined the effect of age on grey matter volume in all three groups. In addition to the whole brain analysis, we chose regions of interest analysis based on previous literature suggesting the involvement of these regions in BECTS or CAE. The group differences of grey matter volume was tested with 2-sample t-test for between two groups' comparisons and ANOVA for three group comparisons.

Results

In the whole brain group comparisons, the grey matter volume in CAE was significantly decreased in the areas of right inferior frontal and anterior temporal compared to BECTS and controls (F_2,67 = 27.53, p < 0.001). In the control group, grey matter volume in bifrontal lobes showed a negative correlation with age (r=-0.54, p < 0.05), whereas no correlation was found in either CAE or BECTS. With ROI analyses, the grey matter volume of posterior thalami was increased in CAE compared to other 2 groups (p < 0.05).

Significance

This study shows that there are grey matter volume differences between CAE and BECTS. Our findings of grey matter volume differences may suggest that there may be localized, specific differences in brain structure between these two types of epilepsy.

SUBMITTER: Fujiwara H

PROVIDER: S-EPMC7494623 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Benign childhood epilepsy with centrotemporal spikes (BECTS) is associated with cognitive and language problems. According to recent studies, disruptions in brain structure and function in children with BECTS are beyond a Rolandic focus, suggesting atypical cortical development. However, previous studies utilizing surface-based metrics (e.g., cortical gyrification) and their structural covariance networks at high resolution in children with BECTS are limited. Twenty-six children with BECTS (15 males/11 females; 10.35 ± 2.91 years) and 26 demographically matched controls (15 males/11 females; 11.35 ± 2.51 years) were included in this study and subjected to high-resolution structural brain MRI scans. The gyrification index was calculated, and structural brain networks were reconstructed based on the covariance of the cortical folding. In the BECTS group, significantly increased gyrification was observed in the bilateral Sylvain fissures and the left pars triangularis, temporal, rostral middle frontal, lateral orbitofrontal, and supramarginal areas (cluster-corrected p < 0.05). Global brain network measures were not significantly different between the groups; however, the nodal alterations were most pronounced in the insular, frontal, temporal, and occipital lobes (FDR corrected, p < 0.05). In children with BECTS, brain hubs increased in number and tended to shift to sensorimotor and temporal areas. Furthermore, we observed significantly positive relationships between the gyrification index and age (vertex p < 0.001, cluster-level correction) as well as duration of epilepsy (vertex p < 0.001, cluster-level correction). Our results suggest that BECTS may be a condition that features abnormal over-folding of the Sylvian fissures and uncoordinated development of structural wiring, disrupted nodal profiles of centrality, and shifted hub distribution, which potentially represents a neuroanatomical hallmark of BECTS in the developing brain.

Project description:RYR2 encodes ryanodine receptor 2 protein (RYR-2) that is mainly located on endoplasmic reticulum membrane and regulates intracellular calcium concentration. The RYR-2 protein is ubiquitously distributed and highly expressed in the heart and brain. Previous studies have identified the RYR2 mutations in the etiology of arrhythmogenic right ventricular dysplasia 2 and catecholaminergic polymorphic ventricular tachycardia. However, the relationship between RYR2 gene and epilepsy is not determined. In this study, we screened for novel genetic variants in a group of 292 cases (families) with benign epilepsy of childhood with centrotemporal spikes (BECTS) by trio-based whole-exome sequencing. RYR2 mutations were identified in five cases with BECTS, including one heterozygous frameshift mutation (c.14361dup/p.Arg4790Pro fs∗6), two heterozygous missense mutations (c.2353G > A/p.Asp785Asn and c.8574G > A/p.Met2858Ile), and two pairs of compound heterozygous mutations (c.4652A > G/p.Asn1551Ser and c.11693T > C/p.Ile3898Thr, c.7469T > C/p.Val2490Ala and c.12770G > A/p.Arg4257Gln, respectively). Asp785Asn was a de novo missense mutation. All the missense mutations were suggested to be damaging by at least three web-based prediction tools. These mutations do not present or at low minor allele frequency in gnomAD database and present statistically higher frequency in the cohort of BECTS than in the control populations of gnomAD. Asp785Asn, Asn1551Ser, and Ile3898Thr were predicted to affect hydrogen bonds with surrounding amino acids. Three affected individuals had arrhythmia (sinus arrhythmia and occasional atrial premature). The two probands with compound heterozygous missense mutations presented mild cardiac structural abnormalities. Strong evidence from ClinGen Clinical Validity Framework suggested an association between RYR2 variants and epilepsy. This study suggests that RYR2 gene is potentially a candidate pathogenic gene of BECTS. More attention should be paid to epilepsy patients with RYR2 mutations, which were associated with arrhythmia and sudden unexpected death in previous reports.