Objective Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) has reported seizure freedom rates between 36% and 78% with at least 1 year of follow‐up. Unfortunately, the lack of robust methods capable of incorporating the inherent variability of patient anatomy, the variability of the ablated volumes, and clinical outcomes have limited three‐dimensional quantitative analysis of surgical targeting and its impact on seizure outcomes. We therefore aimed to leverage a novel image‐based methodology for normalizing surgical therapies across a large multicenter cohort to quantify the effects of surgical targeting on seizure outcomes in LITT for mTLE. Methods This multicenter, retrospective cohort study included 234 patients from 11 centers who underwent LITT for mTLE. To investigate therapy location, all ablation cavities were manually traced on postoperative magnetic resonance imaging (MRI), which were subsequently nonlinearly normalized to a common atlas space. The association of clinical variables and ablation location to seizure outcome was calculated using multivariate regression and Bayesian models, respectively. Results Ablations including more anterior, medial, and inferior temporal lobe structures, which involved greater amygdalar volume, were more likely to be associated with Engel class I outcomes. At both 1 and 2 years after LITT, 58.0% achieved Engel I outcomes. A history of bilateral tonic‐clonic seizures decreased chances of Engel I outcome. Radiographic hippocampal sclerosis was not associated with seizure outcome. Significance LITT is a viable treatment for mTLE in patients who have been properly evaluated at a comprehensive epilepsy center. Consideration of surgical factors is imperative to the complete assessment of LITT. Based on our model, ablations must prioritize the amygdala and also include the hippocampal head, parahippocampal gyrus, and rhinal cortices to maximize chances of seizure freedom. Extending the ablation posteriorly has diminishing returns. Further work is necessary to refine this analysis and define the minimal zone of ablation necessary for seizure control.

Objective To identify features of ablations and trajectories that correlate with optimal seizure control and minimize the risk of neurocognitive deficits in patients undergoing laser interstitial thermal therapy (LiTT) for mesiotemporal epilepsy (mTLE). Methods Clinical and radiographic data were reviewed from a prospectively maintained database of all patients undergoing LiTT for the treatment of mTLE at the University of Miami Hospital. Standard pre- and post-operative evaluations, including contrast-enhanced MRI and neuropsychological testing, were performed in all patients. Laser trajectory and ablation volumes were computed both by manual tracing of mesiotemporal structures and by non-rigid registration of ablation cavities to a common reference system based on 7T MRI data. Results Among 23 patients with at least one-year follow-up, 15 (65%) were free of disabling seizures since the time of their surgery. Sparing of mesial hippocampal head was significantly correlated with persistent disabling seizures (p = 0.01). A lateral trajectory through the hippocampus showed a trend for poor seizure outcome (p = 0.08). Comparison of baseline and postoperative neurocognitive testing revealed areas of both improvement and worsening, which were not associated with ablation volume or trajectory. Significance At one-year follow-up, LiTT appears to be a safe and effective tool for the treatment of mTLE, though a longer follow-up period is necessary to confirm these observations. Better understanding of the impact of ablation volume and location could potentially fine-tune this technique to improve seizure freedom rates and associated neurological and cognitive changes.