Abstracts

Rationale: White matter abnormalities in temporal lobe epilepsy (TLE) have not been fully explored in patients who are lesion-negative on MRI. Apparent Fibre Density (AFD) is a novel quantitative measure derived from diffusion weighted images. AFD is proportional to the intra-axonal volume of water, and is therefore sensitive to pathology-induced changes in white matter axon density. We applied AFD to investigate white matter density in lesion-negative patients and those with hippocampal sclerosis.Methods: Patients with medically refractory unilateral TLE were studied during work-up for epilepsy surgery. Ictal semiology and electrographic onset were confirmed on video-EEG monitoring. 21 patients were lesion-negative, with no relevant lesion on clinical MRI after expert review. 20 patients had MRI features of hippocampal sclerosis. Patients were compared to 52 healthy non-epileptic controls, balanced for age and gender. MRI Analysis: Diffusion-weighted images were acquired on a 3T Siemens Tim Trio (60 directions, b=3000s/mm², 2.5mm³) and analysed with MRTrix. Images were flipped left-right to align the epileptic side. Constrained spherical deconvolution was used to compute fibre orientation distribution (FOD) images, which were non-linearly registered to a symmetrical population-specific template. Within each voxel the Apparent Fibre Density (AFD) was computed from the FOD images. Voxel-wise statistical group comparisons of AFD were performed by t-test, with age, gender and epileptic side as covariates of no interest. Corrected p-values were computed using permutation testing and tractographic threshold-free cluster enhancement. Significant white matter tracts (p<0.05) were displayed using template-derived tractography streamlines.Results: Lesion-negative TLE patients had later onset of seizures and shorter duration of epilepsy than patients with hippocampal sclerosis (table 1). Frequency of seizures was not significantly different. Imaging: Lesion-negative TLE showed a bilateral pattern of decreased AFD compared to controls, affecting corpus callosum, cingulum bundles, inferior fronto-occipital fasciculi, superior longitudinal fasciculi and perpendicular fasciculi. Ipsilateral decreased AFD was seen in thalamo-cortical tracts, superior and inferior cerebellar peduncles (figure 1a). In contrast, the hippocampal sclerosis group showed ipsilateral decreased AFD, in the hippocampal fornix, uncinate fasciculus, cingulum bundle, inferior longitudinal fasciculus, arcuate fasciculus and anterior commissure (figure 1b).Conclusions: Lesion-negative TLE shows decreased AFD, interpreted as decreased intra-axonal volume in specific tracts, in a bilateral pattern involving association and callosal fibres. This differs from hippocampal sclerosis where decreased AFD occurs in the affected temporal lobe and tracts radiating from it. This finding is not easily explained by disease duration or seizure frequency, suggesting that lesion-negative TLE has involvement of differing epileptic networks or epileptogenic processes.