Diffusion MRI Assessment of White Matter Microstructure and Free-Water Fraction in Drug-Naïve Children with SeLECTS.

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 3.0T, 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 to 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.