Increased Immunoglobulin and Proteoglycan Synthesis in Resected Hippocampal Tissue Predicts Post-Surgical Seizure Recurrence in Human Temporal Lobe Epilepsy

<b>Background/Objectives:</b> For patients with medically refractory temporal lobe epilepsy (TLE), surgery is an effective strategy. However, post-operative seizure recurrence occurs in 20-30% of patients, and it remains challenging to predict outcomes solely based on clinical variables. Here, we ask to what extent differences in gene expression in epileptic tissue can predict the outcome after resective epilepsy surgery. <b>Methods:</b> We performed RNAseq on hippocampal tissue resected from eight patients who underwent anterior temporal lobectomy with amygalohippocampectomy (ATL/AH), half of whom became seizure free (SF) or non-seizure free (NSF). <b>Results:</b> Bioinformatic analyses revealed 1548 differentially expressed genes and statistical enrichment analyses identified a distinct set of pathways in NSF and SF cohorts that were associated with neuroinflammation, neurotransmission, synaptic plasticity, and extracellular matrix (ECM) reorganization. Resected tissue exhibiting strong pro-inflammatory processes are associated with better post-surgery seizure outcomes than patients exhibiting cellular signaling processes related to ECM reorganization, autoantibody production, and neural circuit formation. <b>Conclusions:</b> The results suggest that post-operative targeting of both inhibitory aspects of the ECM remodeling and the autoimmune/inflammatory components may be helpful in promoting repair and preventing the recurrence of seizures.