White Matter Microstructural Abnormalities in Neonatal Onset Genetic Epilepsy

OBJECTIVE: Recent evidence indicates that epilepsy is associated with abnormal white matter. If seizures alter white matter, then the impact upon network function, epileptogenesis, and cognition could be pronounced in neonates undergoing rapid developmental myelination. Neonates with epilepsy due to nonstructural genetic causes provide a unique opportunity to determine whether neonates experiencing seizures have abnormal white matter structure. METHODS: This was a retrospective case-control study of term neonates treated in a level IV NICU between 2013 and 2020. Cases had confirmed or suspected genetic epilepsy, normal MRI, and no conditions known to independently impact white matter. Healthy controls had normal MRI and no relevant clinical diagnoses. White matter was assessed via fractional anisotropy (FA) and mean diffusivity (MD) from Diffusion Tensor Imaging (DTI) using Tract Based Spatial Statistics (TBSS). RESULTS: Fifty-eight neonates (19 cases, 39 controls) were included. There was significantly increased FA and decreased MD in the superior corona radiata of neonates with genetic epilepsy compared to healthy controls, controlling for sex and postmenstrual age at time of MRI. Additional association tracts (anterior and posterior corona radiata, tapetum, external capsule, superior and inferior fronto-occipital fasciculus) approached significance (p < 0.2). There was no significant correlation between mean FA or MD and EEG seizure burden or developmental outcome. INTERPRETATION: White matter microstructure is abnormal, with higher FA and lower MD, in major association tracts of neonates with genetic epilepsy compared to healthy controls. These results indicate that white matter is impacted early in neonatal epilepsies, emphasizing the global impact of early-onset seizures.