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Diffusion MRI assessment of white matter microstructure and free-water fraction in drug-naïve children with SeLECTS
Xiaoling Zhou1, Yuwei Chen2, Yu Luo3
1Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, 1617 Riyue Avenue, Qingyang District, Chengdu, 611731, China; Department of Radiology, Affiliated Hospital of Zunyi Medical University, Medical Imaging Center of Guizhou Province, Engineering Research Center of Intelligent Medical Imaging in Guizhou Higher Education Institutions, 149 Dalian Road, Huichuan District, Zunyi, Guizhou, 563000, China.
Background:
Self-limited epilepsy with centrotemporal spikes (SeLECTS) is a common childhood-onset focal epilepsy syndrome. Although seizures are typically self-limited, some children may show neurodevelopmental or cognitive vulnerability. Diffusion MRI may provide insight into white matter alterations in SeLECTS.
Objective:
To evaluate white matter diffusion differences in newly diagnosed, drug-naïve children with SeLECTS using tract-based spatial statistics (TBSS) and white matter free-water fraction (FW-WM), and to explore within-patient associations with selected seizure-related and cognitive variables.
Methods:
Fifty-three newly diagnosed, drug-naïve children with SeLECTS and 53 healthy controls with a similar age and sex distribution were prospectively enrolled in this cross-sectional case-control study. Diffusion MRI was acquired at 3.0 T, and white matter diffusion differences were assessed using TBSS and FW-WM analyses. Voxelwise between-group differences in fractional anisotropy (FA) were tested with age and sex as covariates and corrected using threshold-free cluster enhancement-based family-wise error correction. FW-WM was compared between groups using age- and sex-adjusted general linear models, with additional adjustment for years of education in a sensitivity analysis. Exploratory within-patient associations between imaging measures and selected clinical or cognitive variables were assessed using partial Spearman correlations with false-discovery-rate correction.
Results:
Children with SeLECTS showed lower FA than healthy controls in multiple TBSS-defined white matter regions after correction for multiple comparisons, mainly involving commissural, projection, and association pathways. No between-group differences in mean, axial, or radial diffusivity survived correction for multiple comparisons. FW-WM was higher in the SeLECTS group after adjustment for age and sex (adjusted mean difference = 0.0085; 95% CI, 0.0023-0.0147; P = 0.008), with similar results after additional adjustment for education. In exploratory cluster-level analyses, mean FA in a left-sided cluster involving the posterior internal capsule, posterior thalamic radiation, and sagittal stratum was inversely associated with disease duration after FDR correction (r = -0.413; P = 0.003; q = 0.010). No imaging-cognition or within-patient FW-WM-FA association survived FDR correction.
Conclusions:
Newly diagnosed, drug-naïve children with SeLECTS showed white matter diffusion differences, including lower FA in distributed TBSS-defined regions and higher FW-WM. These findings support diffusion MRI-based characterization of white matter alterations at diagnosis, before antiseizure treatment. Longitudinal studies are needed to clarify their clinical and developmental relevance.
