White matter structural connectivity changes correlate with epilepsy duration in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is thought to be a network disease and structural changes using diffusion tensor imaging (DTI) have been shown. However, lateralized differences in the structural integrity of TLE, as well as changes in structural integrity with longer disease duration, have not been well defined.

We examined the fractional anisotropy (FA) and mean diffusivity (MD) in the hippocampus, as well as its primary (cingulum and fornix) and remote (uncinate and external capsule) connections in both right and left TLE. Changes in diffusion measures over the disease course were examined by correlating FA and MD in the various structures with epilepsy duration. The potential for each measure of anisotropy and diffusivity as a marker of TLE laterality was investigated using random forest (RF) analysis.

MD was increased in the bilateral hippocampus, cingulum, fornix and the right external capsule in both left and right TLE compared to controls. In addition, left TLE exhibited an increased MD in the ipsilateral uncinate fasciculus and bilateral external capsules. A decrease in FA was seen in the left cingulum in left TLE. RF analysis demonstrated that MD of the right hippocampus and FA of the left external capsule were important predictors of TLE laterality. An association of increased MD with epilepsy duration was seen in the left hippocampus in left TLE.

Evidence of disrupted white matter architecture in the hippocampus and its primary and remote connections were demonstrated in TLE. While changes in the hippocampus and cingulum were more prominent in right TLE, remote changes were more prominent in left TLE. MD of the right hippocampus and FA of the left external capsule were found to be the strongest structural predictors of TLE laterality. Changes associated with duration of epilepsy indicated that changes in structural integrity may be progressive over the disease course. This study illustrates the potential of structural diffusion tensor imaging in elucidating pathophysiology, enhancing diagnosis and assisting prognostication.