Rationale: Focal epilepsy in adults is associated with progressive atrophy of the cortex at a rate more than double that of normal aging. It is unknown how to prevent such neurodegeneration. We aimed to determine whether successful epilepsy surgery interrupts progressive cortical thinning. Methods: In this longitudinal case-control neuroimaging study, we included people with unilateral temporal lobe epilepsy (TLE) before (n=29) or after (n=56) anterior temporal lobe resection and healthy volunteers (HV, n=124) matched for 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. Results: Compared to aging-related cortical thinning in healthy volunteers, we found progressive cortical atrophy on vertex-wise analysis in TLE before surgery that was bilateral and localized beyond the ipsilateral temporal lobe (Figure panel A). In these regions, we observed accelerated annualized thinning in left (left TLE 0.0192 ± 0.0014 vs. HV 0.0032 ± 0.0013 mm/year, p< 0.0001) and right (right TLE 0.0198 ± 0.0016 vs. HV 0.0037 ± 0.0016 mm/year, p< 0.0001) presurgical TLE cases (Figure panel C). 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 (Figure panels B and C). Directly comparing the post- vs. 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 aging. Those with postoperative seizures had small areas of continued accelerated thinning after surgery. Conclusions: 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, normalising the rate of atrophy to that of normal aging. These results provide evidence of epilepsy surgery preventing further cerebral damage and provide incentives for offering early surgery in refractory TLE. Funding: Please list any funding that was received in support of this abstract.: None
