Abstracts

Rationale: Diffusion tensor imaging (DTI) is a noninvasive MRI technique that is sensitive to WM architecture of the brain, providing useful information about integrity and fiber orientation of the WM tracts in vivo. In this study we utilized DTI to evaluate changes in WM integrity of JME as compared to controls. We also correlated these WM changes with epilepsy-specific clinical variables, and cognitive measures to investigate the influence of these clinical and cognitive factors on WM integrity changes.Methods: 25 JME patients (15 women, mean age 25.3 years) and 30 control subjects (17 women, mean age 25.5 years) were examined on a 3T MR scanner by using the DTI sequence (30 non-collinear directions with 2 averages). After creating fractional anisotropy (FA) and mean diffusivity (MD) maps for each subject, tract-based spatial statistics (TBSS) was used to compare both FA and MD between patients and controls (TFCE-corrected P<0.01). In order to delineate the possible correlations between the DTI parameters and both clinical and cognitive variables, each patient s FA and MD values of the significant clusters from the TBSS analysis were extracted and then correlated with clinical variables (age of seizure onset, duration of epilepsy, frequency of GTCS) and neuropsychological results (MMSE score, Trail-making part A and B time, Stroop interference time, Letter fluency score, Digit span forward and backward scaled score). Partial correlations controlling for age and education years were used (P<0.05).Results: TBSS demonstrated significant FA reductions in bilateral corona radiata, anterior thalamic radiation, superior longitudinal fasciculus, and body and genu of corpus callosum in JME patients compared to controls. TBSS also showed significant MD increases in brain regions similar to those of FA differences between the groups in JME patients as compared to controls. Neuropsychological assessment showed that JME patients had significantly poorer performance than controls in frontal executive function, attention and working memory domains. Correlation analyses showed a significant negative correlation between the FA values and number of GTCS per 3 years (r=-0.53, P=0.010). There was also a significant positive correlation between the MD values in the significant cluster from TBSS result and number of GTCS (r =-0.565, P=0.005). No additional correlations were found between both FA and MD values and the other clinical variables and the scores of cognitive tests (all P > 0.05).Conclusions: Our findings of altered WM integrity as demonstrated by FA reductions and MD increases as well as frontal executive dysfunctions could support the concept of the thalamofrontal network abnormalities in JME. Additional finding that increased seizure frequency was significantly correlated with both FA decreases and MD increases suggests that repetitive seizure attacks have a consequence on WM integrity in JME. In conclusion, JME is associated with widespread disturbances in frontal microstructural WM integrity and these changes have important cognitive and clinical consequences.