To determine the association between recurrent seizures in neonatal non-structural epilepsy and altered white matter diffusivity.

Increasing evidence demonstrates that myelin is often abnormal in epilepsy; seizures may alter white matter via the recently discovered process of activity-dependent myelination. If seizures alter white matter structure in neonates, the impact upon subsequent neurodevelopment could be pronounced. Neonates are in a period of rapid developmental myelination, making this population unique to study whether recurrent seizures are associated with abnormal white matter development.

This was a retrospective case-control study of term-born neonates who underwent brain MRI at a single institution from 2011-2018. Cases were neonates with non-structural epilepsy due to genetic/presumed genetic etiologies and no conditions present that are known to alter white matter. Controls were healthy neonates with normal MRI. White matter was assessed via mean diffusivity (MD) of the corpus callosum, cingulum, and internal capsules. A multivariable generalized linear model was utilized to determine the association of seizures with MD.

Of 1542 neonatal MRIs completed between 2011-2018, 20 neonates with non-structural epilepsy and 22 healthy controls were identified and included. MD was lower in the genu of the corpus callosum in cases compared to controls (77.1 ± 28.5, p=0.01). MD was also lower in the splenium of the corpus callosum, but this was non-significant (44.7 ± 23.9, p=0.069). There was no difference in the cingulum or internal capsule MD between groups.

MD was lower in the corpus callosum of neonates with recurrent seizures due to non-structural epilepsy as compared to healthy controls. This difference in a major white matter association tract suggests there may be aberrantly increased myelination associated with seizures. Notably, pediatric imaging abnormalities suggestive of aberrantly increased callosal myelination are linked to cognitive dysfunction. Future work will evaluate the association between MD, seizure burden and developmental outcomes.