Abstracts

Myelination in the developing human brain is an age-dependent dynamic event. This maturational process confers a window of vulnerability in which early onset epilepsy may have a greater impact on the eventual integrity of white matter connections than late onset. Using diffusion tensor tractography (DTT), we investigated the effects of age of seizure onset on the volume and structural integrity of the uncinate fasciculus (UF), a major white matter connection between the frontal and temporal lobes., UF volume and fractional anisotropy (FA, an index of white matter integrity and coherence), total brain (TBV), white matter (TWV), and gray matter volume (TGV) were analyzed in 9 patients with focal epilepsy (7=temporal onset; 2=frontal onset) and 9 age- and gender- matched controls. There were 4 patients with early epilepsy, onset prior to age 7, and 5 patients with late epilepsy, onset after age 21. Using FSL (www.fmrib.ox.ac.uk/fsl/), T1-weighted MR images were segmented into gray matter, white matter and CSF. DTT was used to generate probabilistic maps of white matter connectivity of UF in each hemisphere, using the first coronal slice that intersects the UF at the temporal stem as the seed point. The resultant probabilistic maps of connectivity were quantitatively assessed in terms of volume and FA., In early onset epilepsy, the UF ipsilateral to the side of seizure onset showed significant reduction in FA compared to late onset epilepsy (0.250 +/- 0.014 vs. 0.324 +/- 0.013, mean +/- SEM, p[lt] 0.005) and controls (0.250 +/- 0.014 vs. 0.300 +/-0.010, p[lt]0.03). However, there were no differences in the UF FA contralateral to the side of seizure onset or total UF volumes irrespective of side of seizure onset. The TBV is decreased in early onset epilepsy (p[lt]0.05) but not late onset epilepsy (p[gt]0.05) as compared to controls. The TWV also showed significant differences among the three groups (early onset [lt] late onset [lt] controls; ANOVA p[lt]0.01) while TGV remained similar across groups. Among all subjects studied, the extent of reduced FA changes ipsilateral to the side of seizure onset was correlated with reduced TBV (pairwise correlations p[lt].05) and TWV (pairwise correlations p[lt].02), but not TGV (p[gt]0.5)., DTT showed abnormal integrity of frontal-temporal connectivity ipsilateral to the side of seizure onset in early onset epilepsy but not late onset epilepsy. This change in white matter integrity was not evident in the contralateral homologous tract and is not accompanied by reduction in total white matter tract volume. This indicates the differential white matter vulnerability of developing brain to the effects of epilepsy depends on the age of seizure onset., (Supported by NIH T32 NS45540, PI: Baram, T. Z. and GCRC at UC Irvine.)