Effects of surgical targeting in laser interstitial thermal therapy for mesial temporal lobe epilepsy: A multicenter study of 234 patients

Abstract

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.

Keywords: MRI; ablation; amygdalohippocampectomy; stereotactic; surgery.

Figure 1 –

Flowchart of subject selection for analysis of clinical outcomes and calculation of the Engel I outcomes probability map in normalized atlas space.

Figure 2 –

Workflow for image-processing. For each patient, the ablation cavity was manually segmented according to previously-described methods. Preoperative and postoperative images along with the manually-segmented ablation cavity were normalized to a common reference space. Once completed for the entire cohort, a critical population-based analysis of ablation volumes and locations could be performed.

Figure 3 –

Rates of Engel I outcome at 6-month epochs for the entire cohort, the rHS subgroup, and the non-rHS subgroup. Error bars represent the standard error. Univariate regression demonstrated no significant difference in the 95% confidence intervals between the rHS and non-rHS subgroups. Seizure outcomes were durable between 12-months after LITT and at last follow-up.

Figure 4 –

Heat map of the distribution of ablations in 175 patients treated across 11 comprehensive epilepsy centers. Effectively all ablations (red) were centered around the long-axis of the AHC and extended posteriorly to the level of the lateral mesencephalic sulcus. Variation in ablation location is represented by the less frequently ablated regions (green and blue) extending from this central core.

Figure 5 –

Maps representing the positive predictive value (PPV) [A-F] and negative predictive value (NPV) [G-L] of Engel I outcome associated with at least 1-year follow-up for each voxel ablated in normalized atlas space for 175 patients. Panels A and G represent axial views; Panels B and H represent sagittal views; and Panels C-F and I-L represent coronal views through the temporal pole, hippocampal head and posterior amygdala, hippocampal body, and hippocampal tail as represented by the reference lines on the sagittal image. Voxels were assigned a color if it was involved in the ablation of at least 4 patients. Each voxel was analyzed independently. Both maps demonstrate the importance of targeting the anterior, medial, and inferior structures in the mesial temporal lobe. Ablations extending posteriorly beyond the coronal plane in line with the lateral mesencephalic sulcus were less likely to be associated with Engel I outcomes.

Figure 6 –

Theoretical favorable (green) and unfavorable (red) ablation locations based on the PPV and NPV maps. Both ablations are of roughly the same volume, but are located and oriented differently within the mesial temporal structures. The theoretical favorable ablation is located more anteriorly, medially, and inferiorly to cover the high probability voxels for both the PPV and NPV maps. This ablation covers the amygdala, hippocampus, parahippocampal gyrus, and rhinal cortices. The theoretical suboptimal ablation is located more posteriorly, laterally, and superiorly to exclude the high probability voxels for both the PPV and NPV maps. This ablation covers the posterolateral amygdala and hippocampus, but misses a large part of the amygdala, the mesial hippocampal head, parahippocampal gyrus, and rhinal cortices.