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.

Abnormal functional connectivity profiles predict drug responsiveness in patients with temporal lobe epilepsy

“…This could explain the impaired performance of verbal fluency in the NSF group. 34 Based on the widespread cortical thinning and functional connectivity disturbances found in focal epilepsy, 2,5,14 epilepsy is now considered a network disorder. Although the mechanism underlying insufficiently deactivated DMN is not fully understood, the interruption of connectivity caused by hippocampal abnormalities could be one reason for it.…”

“…Our model provided an accuracy of >85% in predicting the outcome of NSF and discriminating drug-resistant patients before clinical diagnosis, validated by the neural network classification model. Given that epilepsy is associated with an increased risk of mortality, 1 cognitive decline, 9 and cortex atrophy, 2,5 predicting responsiveness to the current prescription would shorten the time span of ASM trials and allow patients to be referred for surgical evaluation earlier, leading to better clinical outcomes. 1,2,8 We performed several sensitivity analyses to evaluate the effects of potential confounders.…”

“…Given that epilepsy is associated with an increased risk of mortality, 1 cognitive decline, 9 and cortex atrophy, 2,5 predicting responsiveness to the current prescription would shorten the time span of ASM trials and allow patients to be referred for surgical evaluation earlier, leading to better clinical outcomes. 1,2,8 We performed several sensitivity analyses to evaluate the effects of potential confounders. To evaluate the lateralization effect, we performed sensitivity analyses in the LTLE and RTLE subgroups.…”

“…The outcome of antiseizure medication (ASM) treatment can be classified as seizure freedom (SF) and non-seizure freedom (NSF), 1,2 and temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy in adults. 3 Given that continuing seizures are associated with progressive damage to brain structure 2,[4][5][6] and function, [7][8][9] several studies have explored predictive and risk factors for drug-resistant epilepsy in clinical and demographic data [10][11][12][13] and highlighted the contribution of hippocampal abnormalities. 12,13 As part of the Papez circuit, the hippocampus is at the center of seizure generation and propagation.…”

Flattening the Curve: Slowing Age-Accelerated Brain Atrophy With Epilepsy Surgery

“…In the highlighted article, Galovic et al 9 build upon their previous findings of progressive brain atrophy in focal epilepsy and ask the question, what impact does resective surgery have on progressive cortical thinning in TLE and does this differ in patients with seizure-free versus non seizure-free outcomes ? The authors examined annualized atrophy rates in patients with TLE who had paired structural magnetic resonance imaging scans at least six months apart either before (N = 29) or after (N = 56) anterior temporal lobe resection and compared their annualized atrophy rates to 124 age- and sex-matched healthy controls.…”