Abstract
Despite evidence for microstructural brain alterations in epilepsy patients, little is known about how these develop with age and the progress of the disease. The aim of this study was to investigate microstructural abnormalities of the white matter (WM) in children with new-onset, untreated idiopathic-generalized epilepsy (IGE) using the MRI technique of diffusion tensor imaging (DTI). The study was approved by the institutional review board, and all individuals or their parents gave signed informed consent. In total, 45 patients with IGE (age 5–18 years, male: female 26:19) and 32 healthy controls (HCs; age 5–18 years, male: female 21:11) were included. Voxel-based analysis (VBA) was used to compare patients and controls, and Pearson correlation analysis was used to investigate relationships between altered DTI metrics and clinical parameters. Compared with controls, patients with IGE showed increased mean diffusivity (MD) in the left splenium of the corpus callosum, increased fractional anisotropy (FA) in the right WM of the superior and middle frontal gyri, increased axial diffusivity (AD) in the WM of right corona radiata and left occipital lobe, and decreased AD in the WM of the left thalamus and the right middle cerebellar peduncle. There was no correlation between the altered diffusion parameters and clinical measures. Our study demonstrated several distinct microstructural impairments in children with new-onset, untreated IGE, of which altered AD might be the most sensitive marker of dysmyelination. The increased FA in the IGE group might suggest an initiating or compensatory mechanism that is activated prior to cognitive decline in these children.
Highlights
Epilepsy is one of the commonest non-communicable neurologic conditions and a significant cause of disability and mortality, affecting 70 million people worldwide [1]
Abnormal diffusion tensor imaging (DTI) in Children Epilepsy latest International League Against Epilepsy (ILAE) classification [5, 6], idiopathic-generalized epilepsy (IGE) includes 4-well established epilepsy syndromes— childhood absence epilepsy (CAE), juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and generalized tonic-clonic seizures (GTCS)— not all patients are classifiable in these terms
There was no significant difference in mini-mental state examination (MMSE) scores between IGE and healthy controls (HCs) groups
Summary
Epilepsy is one of the commonest non-communicable neurologic conditions and a significant cause of disability and mortality, affecting 70 million people worldwide [1]. Idiopathic-generalized epilepsies (IGE) are characterized by absence, myoclonic, and generalized tonic-clonic seizures (GTCS), which can present alone or in various combinations. MRI has been widely used to investigate in vivo structural and functional changes in neuropsychiatric diseases, such as epilepsy. The MRI technique of diffusion tensor imaging (DTI), which is sensitive to the directionally constrained water diffusion along myelinated axons [7], has provided new opportunities for studying hemispheric differences in microscopic fiber characteristics. Several parameters can be used to quantify this tissue water diffusion: fractional anisotropy (FA) and mean diffusivity (MD) are widely used as markers of the microstructural integrity of white matter (WM) [8, 9]; radial diffusivity (RD) and axial diffusivity (AD) represent water diffusion perpendicular and parallel to the axonal fibers, respectively. The magnitude and direction of diffusivity depend on the WM microstructure [10] and can reveal epileptogenic lesions that are not visible using conventional MRI
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