Effective Connectivity in Epileptic Hypothalamic Hamartomas

Hypothalamic hamartomas (HH) are rare, non-cancerous tumors that are located deep within the brain. HH often cause drug-resistant epilepsy (DRE), and surgery is the primary treatment for HH-related epilepsy. However, the rates of patients who don’t experience seizures after surgery (postoperative seizure freedom rates) are inconsistent. One contributing factor for the inconsistent seizure freedom rates may be seizure propagation, the area where seizure activity spreads from, through mesial temporal structures, which are not fully captured in conventional clinical machines. The primary structures within the mesial surface of the temporal lobe are the hippocampus, amygdala, and parahippocampal gyrus. The mesial surface of the temporal lobe has been found to be highly related to the pathogenesis of mesial temporal lobe epilepsy due to its highly complex function and location between the temporal lobe and the rest of the brain.   To increase postoperative seizure freedom rates, we wanted to investigate a novel avenue for determining surgical candidacy. Resting-state functional MRI (rs-fMRI) with Dynamic Causal Modeling (DCM) is a non-invasive method to assess directional seizure-network dynamics with greater precision. DCM provides quantitative and qualitative data on the intensity of connectivity signaling and the directional flow within the brain. Understanding whether the connectivity values from DCM predict postoperative seizure reduction is a necessary step toward improving surgical outcomes and planning. We hypothesized that stronger inhibitory signaling back to the HH from the hippocampal heads is associated with patients who experience higher post-surgical seizure freedom. Additionally, weaker or absent inhibitory signals characterize worse outcomes after HH-only ablation. In this study, we examined 43 patients with HH-related epilepsy between the HH, the seizure onset zone (SOZ), and the left and right hippocampal heads, which is the anterior side of the hippocampus. The results revealed that increased inhibitory signaling from the hippocampi to the HH was strongly associated with greater postoperative seizure reduction. These results can be used as a basis for clinicians to identify better surgical candidates who will have higher post-surgical seizure freedom rates.