Resective surgery prevents progressive cortical thinning in temporal lobe epilepsy

Abstract

Focal epilepsy in adults is associated with progressive atrophy of the cortex at a rate more than double that of normal ageing. We aimed to determine whether successful epilepsy surgery interrupts progressive cortical thinning. In this longitudinal case-control neuroimaging study, we included subjects with unilateral temporal lobe epilepsy (TLE) before (n = 29) or after (n = 56) anterior temporal lobe resection and healthy volunteers (n = 124) comparable regarding age and sex. We measured cortical thickness on paired structural MRI scans in all participants and compared progressive thinning between groups using linear mixed effects models. Compared to ageing-related cortical thinning in healthy subjects, we found progressive cortical atrophy on vertex-wise analysis in TLE before surgery that was bilateral and localized beyond the ipsilateral temporal lobe. In these regions, we observed accelerated annualized thinning in left (left TLE 0.0192 ± 0.0014 versus healthy volunteers 0.0032 ± 0.0013 mm/year, P < 0.0001) and right (right TLE 0.0198 ± 0.0016 versus healthy volunteers 0.0037 ± 0.0016 mm/year, P < 0.0001) presurgical TLE cases. Cortical thinning in these areas was reduced after surgical resection of the left (0.0074 ± 0.0016 mm/year, P = 0.0006) or right (0.0052 ± 0.0020 mm/year, P = 0.0006) anterior temporal lobe. Directly comparing the post- versus presurgical TLE groups on vertex-wise analysis, the areas of postoperatively reduced thinning were in both hemispheres, particularly, but not exclusively, in regions that were affected preoperatively. Participants who remained completely seizure-free after surgery had no more progressive thinning than that observed during normal ageing. Those with postoperative seizures had small areas of continued accelerated thinning after surgery. Thus, successful epilepsy surgery prevents progressive cortical atrophy that is observed in TLE and may be potentially neuroprotective. This effect was more pronounced in those who remained seizure-free after temporal lobe resection, normalizing the rate of atrophy to that of normal ageing. These results provide evidence of epilepsy surgery preventing further cerebral damage and provide incentives for offering early surgery in refractory TLE.

Keywords: MRI; epilepsy; neurodegeneration; seizures; surgery.

Figure 1

Progressive cortical thinning in pre- and postsurgical epilepsy and healthy volunteers. Comparison of progressive cortical thinning in pre- (A) and postsurgical (B) epilepsy cohorts with healthy volunteers. Significant clusters (P < 0.05, correction for multiple comparisons using random field theory) and the mean resection extent are superimposed on hemispheric surface templates. Blue clusters indicate progressive atrophy, red colours indicate progressive hypertrophy, resection extent is displayed in shades of purple. FWE = familywise error. (C) Regional cortical thickness estimates and the predicted rate of regional cortical thinning in healthy control subjects (grey), pre- (blue) and postoperative (orange) TLE patients. Each scan is represented by a dot and scans corresponding to the same patient are connected by a thin line. The three thick lines are linear regression lines of mixed effects models and their slopes represent the estimated rate of cortical thinning in each group. Because mixed effects models were fitted with a variable intercept, all linear regression lines were adjusted to have the same intercept. The graph shows an accelerated rate of cortical thinning in preoperative TLE patients compared to healthy controls. This rate is largely normalized in postoperative TLE patients. The analysed regions were defined as those areas that showed significant cortical thinning before surgery in A.

Figure 2

Direct comparison of progressive cortical thinning after versus before surgery. Comparison of progressive cortical thinning in postsurgical versus presurgical patients with left (A) or right (B) TLE. Significant clusters (P < 0.05, correction for multiple comparisons using random field theory) and the mean resection extent are superimposed on hemispheric surface templates. Blue clusters indicate accelerated atrophy after surgery, red colours indicate reduced atrophy after surgery, resection extent is displayed in shades of purple.

Figure 3

Direct within-subject comparison of progressive cortical thinning after versus before surgery. Comparison of within-subject changes to progressive cortical thinning in a subgroup of eight patients with left TLE who had both pre- and postsurgical paired scans. Significant clusters (P < 0.05, correction for multiple comparisons using random field theory) and the mean resection extent are superimposed on hemispheric surface templates. Blue clusters indicate accelerated atrophy after surgery, red colours indicate reduced atrophy after surgery, resection extent is displayed in shades of purple.

Figure 4

Progressive cortical thinning in non-seizure-free and seizure-free postsurgical epilepsy patients versus healthy volunteers. Comparison of progressive cortical thinning in non-seizure-free and seizure-free postsurgical epilepsy patients with healthy control subjects. Significant clusters (P < 0.05, correction for multiple comparisons using random field theory) and the mean resection extent are superimposed on hemispheric surface templates. Blue clusters indicate accelerated atrophy after surgery, red colours indicate reduced atrophy after surgery, resection extent is displayed in shades of purple.