Abstracts

Rationale: Mesial temporal lobe epilepsy (mTLE) can compromise white matter (WM) integrity. Unilateral mTLE is often associated with subclinical seizure (interictal) activity in the contralateral mesial temporal lobe - the effects of this contralateral interictal seizure burden (cItSb) on WM integrity have not been investigated. We hypothesized that mTLE patients will show proximal and distal white matter deterioration relative to healthy controls, with the left TLE patients showing more pronounced deterioration; and that mTLE patients with cItSb would show more pronounced deterioration than patients with unilateral interictal activity. Methods: We used tract based spatial statistics, an advanced registration technique, to assess WM integrity in regions proximal and distal to the epileptogenic temporal lobe, utilizing region-of-interest and whole brain analyses, respectively. Patients were grouped based on side of ictal seizure focus, and based on the presence or absence of cItSb, based upon extensive video-EEG monitoring. GLM based statistical analyzes emphasized fractional anisotropy (FA) differences between mTLE patients and controls, and between each patient grouping. Results: Our data demonstrates that mTLE patients, compared to controls, showed decreased FA in: (1) a large bilateral middle and inferior frontal region and (2) based on region-of-interest analyses involving the epileptogenic and contralateral/nonepileptogenic temporal lobe - the bilateral temporal lobes; both of these finding appeared independent of the side of seizure focus, or the presence of cItSb. Lastly, compared to patients with unilateral interictal activity, cItSb patients showed increased FA in a posterior cross-hemispheric region (splenium and forceps major). Conclusions: These results suggest that unilateral mTLE compromises WM integrity within and beyond the epileptogenic temporal lobe, with extra-epileptogenic deterioration observed in the bilateral inferior/middle frontal, and contralateral anterior/mesial temporal lobes. These findings are consistent with prior literature showing that focal/unilateral mTLE has a widespread anatomical impact. Our results suggest the presence of contralateral interictal seizure burden has a very selective effect, enhancing WM integrity in a specific posterior cross-hemispheric region. This finding, while counter-intuitive in relation to the hypothesized effects of increased seizure burden, suggests that contralateral--homologous interictal seizure burden increases posterior/cross-hemispheric WM integrity. Thus, the data demonstrate the complexities in understanding the effect of seizures (propagation, interictal activity, epileptogenesis) on WM; highlighting the need for considering WM integrity and the effects of contralateral interictal seizure burden when modeling the effects of epilepsy on brain regions outside the ictal focus.