Anatomy-corrected metabolic asymmetry predicts seizure freedom after surgery in focal cortical dysplasia

Precise lesion localisation is central to favourable surgical outcomes in patients with drug-resistant epilepsy due to focal cortical dysplasia. We validated the Anatomy-Corrected Asymmetry Index of fluorodeoxyglucose positron emission tomography to objectively delineate regions of hypometabolism and predict surgical outcome in patients with focal cortical dysplasia. We first established normative Anatomy-Corrected Asymmetry Index thresholds using five independent and heterogeneous healthy control cohorts (n = 179) to assess reproducibility. We subsequently validated our findings in 40 pathologically confirmed focal cortical dysplasia patients who underwent resective surgery. The primary analysis assessed the association between the extent of resection of defined hypometabolic clusters and 24-month seizure freedom (Engel Class I). After excluding subjects with segmentation artefacts to ensure accurate threshold definition, we established a normative threshold of -19 with a minimum cluster size of 2.0 mL. In the patient cohort, 29 subjects had high-quality segmentations. Patients with at least one localising cluster achieved significantly higher seizure freedom rates compared to those without clusters (76.5% vs. 22.2%, P = 0.014). The percentage of resected hypometabolic volume was significantly associated with Engel Class I outcome (P = 0.011). Sensitivity analysis demonstrated that a more permissive threshold of -16 identified localising clusters in two additional seizure-free patients who were false negatives at the standard threshold. The Anatomy-Corrected Asymmetry Index provides a standardised metric that predicts seizure freedom in focal cortical dysplasia epilepsy surgery. Clinical implementation requires rigorous quality control of anatomical segmentations to ensure diagnostic accuracy.