Abstracts

Rationale: Absence epilepsy involves abnormal interaction of corticothalamocortical networks. Diffusion tensor imaging (DTI) measures the diffusion properties of water in tissue and provides a noninvasive method for assessing white matter microstructure which allows detection of differences between healthy and non-healthy brains. The aim of this study is to assess potential morphological changes in childhood absence epilepsy (CAE) in human patients as well as in a well-established CAE animal model. Methods: We performed DTI on children with CAE (n = 9) and age and sex matched normal children (n = 10). We used Wistar albino Glaxo rats of Rijswijk (WAG/Rij), a genetic model of CAE, without treatment (n = 10), and WAG/Rij rats after 4 months of chronic treatment (n = 9) started at age 30 day with the antiabsence medicine ethosuximide. Children were imaged on a 3T and rats on a 9.4T system. Data was processed using Bioimagesuite (www.bioimagesuite.org, Yale University, MRRC). Eigenvalues were calculated from the diffusion tensor matrix, and DTI metrics, including fractional anisotropy (FA) were determined. Registration of the imaging data (to a template brain from control group in each study) involved rigid-body and non-linear registration of T2-weighted structural images via a tensor b-spline algorithm; the composite transformation was then applied to all FA maps and other DTI metrics. FA maps were thresholded and a two sample t-test was performed to assess differences in FA between control and disease groups. Results: Children with CAE show significantly decreased FA in the posterior white matter, forceps major region. The occipital and medial parietal cortices were found to be involved in separate fMRI studies of these children. Anterior corpus callosum of treated WAG/Rij rats showed increased FA compared to untreated WAG/Rij rats, suggesting there is some recovery in neuronal pathway morphology after antiepileptogenic ethosuximide treatment. In another previous study, we found that the tissue integrity of the anterior corpus callosum was compromised in epileptic rats. Decrease in FA may involve reduced axonal density connecting and/or affected myelin integrity in this network connection intensely involved brain regions during absence seizures in children as well as in animal model. Conclusions: Our studies show that DTI can detect subtle white matter changes due to recurrent spontaneous seizures in CAE children as well as improvement in white matter pathways in an animal treatment model due to antiepileptogenic ethosuximide treatment. These results are crucial for better understanding the CAE disease process and suggest that DTI may ultimately serve as a disease biomarker in a noninvasive manner in human therapeutic trials in absence epilepsy. Grant Support: R01 NS-049307 (to HB); 5R01NS055829-04 (to HB). Religious Conflict: Saturday PM.