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

Background/Objectives: 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 outcome solely based on clinical variables. Here we ask to what extent differences in gene expression in epileptic tissue can predict outcome after resective epilepsy surgery. Methods: We perform RNAseq on hippocampal tissue resected from 8 patients who underwent anterior temporal lobectomy with amygalohippocampectomy (ATL/AH), half of whom became seizure free (SF) or non-seizure free (NSF). Results: Bioinformatic analyses revealed 1548 differentially ex-pressed 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 ex-hibiting strong proinflammatory processes are associated with better post-surgery seizure outcomes than patients exhibiting cellular signaling processes related to ECM reorgan-ization, autoantibody production and neural circuit formation. Conclusions: The results suggest that postoperative 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.