Epilepsy Fellow Children's Hospital of Philadelphia
Rationale: Increasing evidence suggests that white matter structure is abnormal in various forms of epilepsy. Seizures may alter white matter through maladaptive mechanisms of plasticity. If seizures alter white matter 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. Methods: 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 with normal brain MRI and no other conditions present that are known to alter white matter. Controls were healthy neonates with normal MRI. White matter was assessed via region of interest analysis for quantitative mean diffusivity (MD) of the genu and splenium of the corpus callosum, cingulum, and internal capsules by two child neurologists blinded to the clinical history. Mean MD of the specified tracts were compared between cases and controls using multivariable linear regression models, adjusting for gestational age and post-conceptional age at time of MRI. Results: Of 1,542 neonatal MRIs completed between 2011-2018, 22 neonates with non-structural epilepsy and 22 unmatched healthy controls were identified and included. MD was significantly 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). MD measurements in the cingulum and internal capsule had lower interobserver agreement and were therefore not further analyzed. Conclusions: MD was lower in the genu of the corpus callosum of neonates with recurrent seizures as compared to healthy controls. This suggests that in neonatal non-structural epilepsy, seizures may induce aberrant myelination or lack of axonal pruning in developing white matter. Future work will further evaluate the precise nature of white matter structural changes and the potential associations between MD, seizure burden and developmental outcomes. Funding: Please list any funding that was received in support of this abstract.: Dr. Knowles is supported by NIH/NINDS K12NS098482-02, a Taking Flight Award from the CURE Foundation, and the Stanford Maternal and Child Health Research Institute. Dr. Wusthoff is supported by NIH/NINDS K02NS102598. Support for the Stanford Quantitative Sciences Unit was provided by the Stanford Department of Neurology.
