The Spatial Divergence of Hypometabolism and Atrophy in Mesial Temporal Lobe Epilepsy: Combining 18F‐FDG PET and Structural MRI for Predicting Postoperative Seizure Freedom
Aug 2026· Human Brain Mapping· Vol 47· 0 citations· 44 references
Medicine
TL;DR
This comprehensive preoperative clinical‐imaging model achieved robust prognostic efficacy that was not significantly improved by the addition of actual postoperative resection volumes, and demonstrates significant synergistic potential for predicting surgical outcomes.
Abstract
Surgical failure in temporal lobe epilepsy with hippocampal sclerosis (TLE‐HS) may reflect insufficient disruption of epileptogenic networks. We investigated whether integrating quantitative spatial patterns of regional atrophy and hypometabolism, along with clinical features, could provide complementary prognostic information for postoperative seizure freedom. T1‐weighted MRI, 18F‐FDG‐PET, and postoperative CT scans of patients with TLE‐HS were retrospectively analyzed against a validated healthy control cohort to compute age‐ and gender‐adjusted W‐score maps. Regional relationships of atrophy and hypometabolism were assessed using bivariate correlations and multiple regression analyses. Machine learning models integrating laterality of seizure onset, preoperative (extra‐)temporal atrophy/hypometabolism extent, seizure frequency, focal to bilateral tonic–clonic seizures during the preceding year, and resection volume were developed to predict seizure freedom 1 year after surgery. Model interpretability was assessed via permutation‐based variable importance analysis. The cohort comprised 101 patients with TLE‐HS (48 left, LHS; 53 right, RHS), including 72 patients who underwent anterior temporal lobectomy. Distinct modality‐specific patterns emerged: hypometabolism was significantly greater than local atrophy in left temporo‐limbic cortex in TLE‐LHS, while atrophy exceeded hypometabolism in bilateral occipital regions in TLE‐RHS. Positive correlations between local atrophy and hypometabolism were more robust in ipsilateral temporo‐limbic cortex in TLE‐LHS. The combined model integrating preoperative atrophy and hypometabolism features (AUC: 0.56–0.64) significantly outperformed single‐modality models (pfdr < 0.05). Notably, incorporating clinical factors further enhanced predictive performance (AUC: 0.63–0.70) and model calibration. This comprehensive preoperative clinical‐imaging model achieved robust prognostic efficacy that was not significantly improved by the addition of actual postoperative resection volumes. Structural MRI and 18F‐FDG‐PET reveal complementary facets of the epileptogenic network in TLE‐HS. While integrating multimodal imaging with clinical metrics demonstrates significant synergistic potential for predicting surgical outcomes, our models remain exploratory. External validation in independent multi‐center cohorts is required before translating these findings into precise clinical tools for surgical planning.
A hypometabolic gradient is identified in TLE, which covaries with cytoarchitectonic organization, microstructural changes, and hippocampal-neocortical interactions and provides a biologically grounded framework for precise surgical planning, emphasizing that targeting severe hypometabolism may optimize prognosis.
J. Mo, F. Fadaie, J. Lam et al.· medRxiv· 0 citations
Background: Interictal [18F]FDG-PET is commonly used for temporal lateralization in mesial temporal lobe epilepsy (mTLE). Whether atlas-based quantitative PET measures differ according to surgical outcome among otherwise concordant unilateral MRI-positive mTLE patients remains uncertain. This study compared preoperative FDG-PET ROI measures between 2-year Engel outcome groups using SPM-assisted spatial normalization followed by AAL atlas-based ROI analysis. Methods: Among 319 screened temporal lobe epilepsy surgery patients, 94 had evaluable preoperative FDG-PET images, and 62 patients with at least 2 years of postoperative follow-up were included in the total cohort. The primary quantitative analysis was restricted to 54 unilateral MRI-positive patients with hippocampal atrophy and mesial temporal sclerosis on MRI (Engel I, n = 45; Engel II–IV, n = 9). Cerebellum-normalized AAL ROI uptake ratios were compared using Mann–Whitney U tests in conventional left/right and ipsilateral/contralateral analyses. FDR-adjusted q values, effect sizes, and Hodges–Lehmann median differences with 95% confidence intervals were calculated. Reference-region and global mean normalization sensitivity analyses were also performed. Results: In the unilateral MRI-positive subgroup, 10 of 80 conventional left/right ROIs showed unadjusted differences between Engel I and Engel II–IV patients, predominantly involving left frontal-orbitofrontal, medial frontal, middle cingulate, and inferior parietal regions. After ipsilateral/contralateral transformation, eight ROIs showed unadjusted group differences, mainly in contralateral frontal-orbitofrontal regions, with additional cingulate and inferior parietal involvement. Uptake ratios were lower in Engel II–IV patients in all candidate ROIs. However, none of the ROI findings survived FDR correction. Raw cerebellar uptake did not differ between outcome groups, and global mean normalization did not yield FDR-corrected ROI findings. Conclusions: Quantitative ROI analysis identified several extratemporal metabolic differences between postoperative outcome groups; however, none remained significant after correction for multiple comparisons. These findings should therefore be considered exploratory and hypothesis-generating rather than evidence that quantitative FDG-PET can discriminate surgical outcomes. Larger, adequately powered cohorts are needed before the potential clinical utility of quantitative FDG-PET analysis in presurgical evaluation can be determined.
Long-term outcomes in temporal lobe epilepsy depend not only on accurate localization and removal of epileptogenic tissue but also on how its connectivity is distributed across brain networks before surgery, which may represent a biomarker of late relapse.
V.Yu. Karpychev, Rebecca W. Roth, K. Davis et al.· Epilepsia· 0 citations