Abstracts

Rationale: We are presently conducting a prospective study on children with new-onset partial seizures and normal conventional MRI scans. In the present analysis, we used diffusion tensor MR imaging and Tract Based Spatial Statistics (TBSS; Smith SM et al., Neuroimage, 2006; 31:1487) to objectively analyze water diffusion related changes in the cerebral white matter of this group of children. Methods: Ten right-handed children with recent onset epilepsy (age: 5-11 years, mean age: 7.6+1.9, 4 boys) were compared to eight right-handed healthy control subjects (age: 6-11 years, mean age: 8.4±1.8, 2 boys). All the children had normal conventional MRI. The normal children were studied with Institutional Review Board approval, as long as sedation was not used. TBSS analysis involved nonlinear registration of individual fractional anisotropy (FA) maps to a template image, skeletonization of the FA map, followed by voxel-wise statistical comparison of the skeletonized FA and apparent diffusion coefficient (ADC) maps of the two groups (controls and patients), with age as a covariate. Regions with significant differences were isolated and the mean FA and ADC values of the skeletons were correlated with clinical data such as, age, age at seizure onset, and duration of epilepsy. Results: TBSS showed regions with significantly decreased FA in the right cortico- spinal tract (R-CST) at the level of midbrain, left frontal white matter (L-FWM), and left and right superior longitudinal fasciculus (L-SLF, R-SLF) in the epilepsy group compared to the controls. The mean FA value of L-SLF and L-FWM showed significant a negative correlation with age of seizure onset (r=-0.0637 p=0.047 and r=-0.748 p=0.013), respectively. In addition, mean FA value of L-FWM showed a significant negative correlation (r=-0.697 p=0.025) with age at the time of the MRI scan. No such correlations were seen in the controls. TBSS analysis of ADC maps showed no regional differences between controls and patients. Conclusions: This objective analysis on a relatively small sample revealed white matter regions with abnormal diffusion properties in 4 regions involving both hemispheres of patients with recent onset epilepsy. During normal maturation, FA values should generally increase with age prior to adolescence due to myelination, axonal pruning and other factors. However, in the children with new-onset epilepsy of this study, several regions in the left hemisphere showed a reverse finding of abnormally decreasing FA values with age. These findings suggest widespread white matter pathology even in the early stages of clinical epilepsy, which may be due to genetic or other pre-existing factors.