Objectives: Whether febrile seizures (FS) produce long-term injury to the hippocampus or other brain structures is a critical question concerning focal onset seizures in children. Our aims are to evaluate the effect of FS on subfields of the hippocampus, thalamic nuclei, amygdala, cortical thickness, and surface area quantitatively in children with FS who later developed focal seizures and to identify biomarkers based on MRI structures. Methods: Children who had focal onset seizures with or without previous FS and normal 3-T MRI findings were included retrospectively. The MRI was performed within 2 years after the onset of focal seizures. Age-matched controls were also recruited. Hippocampal subfields and thalamic nuclei, amygdala volumes, cortical thickness, and cortical surface area in individual cortical regions were segmented by FreeSurfer version 7.1.1. Volumetric and morphometric data among children who had focal seizures with or without previous FS, as well as controls, were compared and correlated with clinical parameters. Results: Children with a history of FS who had focal seizures exhibited smaller right cornu ammonis (CA) 1 and right molecular cell layer of the hippocampus, compared to those without FS. A larger left hippocampal fissure was also found in FS with focal seizures compared to age-matched controls. There were no statistically significant differences in each nucleus of the thalamus, amygdala, cortical thickness, and surface area of each cortical region among the three groups. A smaller whole hippocampal volume was found for the right hippocampus in children with FS and focal seizures compared to those without FS. A trend of negative correlation was found between the frequency of FS and the left and right CA1 subfield volume ratios of the hippocampus. Conclusions: We concluded that multiple episodes of FS may be associated with a trivial difference in volume reduction in the CA1 and molecular layer of the right hippocampus and an enlarged hippocampal fissure of the left hippocampus, but not with individual cortical thicknesses, surface area, thalamic nuclei, or amygdala in children with focal onset seizures.The hippocampal subfield CA1 and molecular layer of the right hippocampus may be more vulnerable than the cortices in children with focal seizures who experienced multiple FS episodes. This study highlights the minimal differences in brain volumes among children with recent onset focal seizures with or without FS history and controls, suggesting that the brain injurious aspects of the FS and recent onset focal seizures may have been previously overstated. This suggests that physicians can be reassuring about brain injury associated with these seizure types when discussing outcomes with parents and patients.
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