White Matter Microstructural Abnormalities in Neonatal Onset Genetic Epilepsy
Amanda G Sandoval Karamian1, Tianjia Zhu2,3, Hao Huang2,4
1Division of Neurology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, Utah, USA.
Annals of Clinical and Translational Neurology
|May 23, 2026
Summary
Neonatal genetic epilepsy is linked to abnormal white matter microstructure, specifically higher fractional anisotropy (FA) and lower mean diffusivity (MD) in key brain pathways. These findings highlight early white matter impacts in infant epilepsy.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Pediatric Neurology
Background:
- Epilepsy in neonates is associated with white matter abnormalities.
- Rapid myelination during infancy may amplify seizure-induced white matter changes, affecting brain networks, epileptogenesis, and cognition.
- Genetic epilepsies without structural brain abnormalities in neonates offer a model to study seizure-related white matter alterations.
Purpose of the Study:
- To investigate white matter structure in neonates with genetic epilepsy.
- To determine if seizures in neonates impact white matter integrity during a critical developmental period.
Main Methods:
- Retrospective case-control study of term neonates (2013-2020).
- Cases: genetic epilepsy, normal MRI, no confounding conditions. Controls: healthy, normal MRI.
- Diffusion Tensor Imaging (DTI) assessed white matter using fractional anisotropy (FA) and mean diffusivity (MD) via Tract Based Spatial Statistics (TBSS).
Main Results:
- Fifty-eight neonates (19 cases, 39 controls) were analyzed.
- Significantly increased FA and decreased MD observed in the superior corona radiata of neonates with genetic epilepsy versus controls.
- Other association tracts showed trends toward significance; no correlation found between FA/MD and seizure burden or outcome.
Conclusions:
- Neonates with genetic epilepsy exhibit altered white matter microstructure (higher FA, lower MD) in major association tracts.
- These findings demonstrate early white matter impact in neonatal epilepsies.
- Early-onset seizures have a global effect on developing white matter in neonates.
