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....

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Main Authors: Michael F. Hammer, Martin E. Weinand
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Pathophysiology
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Online Access:https://www.mdpi.com/1873-149X/32/2/15
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author Michael F. Hammer
Martin E. Weinand
author_facet Michael F. Hammer
Martin E. Weinand
author_sort Michael F. Hammer
collection DOAJ
description <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.
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spelling doaj-art-1f94761e7dd64a92bded6c8de1102ea72025-08-20T03:16:24ZengMDPI AGPathophysiology1873-149X2025-04-013221510.3390/pathophysiology32020015Increased Immunoglobulin and Proteoglycan Synthesis in Resected Hippocampal Tissue Predicts Post-Surgical Seizure Recurrence in Human Temporal Lobe EpilepsyMichael F. Hammer0Martin E. Weinand1BIO5 Institute, University of Arizona, Tucson, AZ 85721, USADepartment of Neurosurgery, University of Arizona College of Medicine, Tucson, AZ 85724, USA<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.https://www.mdpi.com/1873-149X/32/2/15temporal lobe epilepsysurgery outcomeautoantibodiesneuroinflammationtranscriptometemporal lobectomy
spellingShingle Michael F. Hammer
Martin E. Weinand
Increased Immunoglobulin and Proteoglycan Synthesis in Resected Hippocampal Tissue Predicts Post-Surgical Seizure Recurrence in Human Temporal Lobe Epilepsy
Pathophysiology
temporal lobe epilepsy
surgery outcome
autoantibodies
neuroinflammation
transcriptome
temporal lobectomy
title Increased Immunoglobulin and Proteoglycan Synthesis in Resected Hippocampal Tissue Predicts Post-Surgical Seizure Recurrence in Human Temporal Lobe Epilepsy
title_full Increased Immunoglobulin and Proteoglycan Synthesis in Resected Hippocampal Tissue Predicts Post-Surgical Seizure Recurrence in Human Temporal Lobe Epilepsy
title_fullStr Increased Immunoglobulin and Proteoglycan Synthesis in Resected Hippocampal Tissue Predicts Post-Surgical Seizure Recurrence in Human Temporal Lobe Epilepsy
title_full_unstemmed Increased Immunoglobulin and Proteoglycan Synthesis in Resected Hippocampal Tissue Predicts Post-Surgical Seizure Recurrence in Human Temporal Lobe Epilepsy
title_short Increased Immunoglobulin and Proteoglycan Synthesis in Resected Hippocampal Tissue Predicts Post-Surgical Seizure Recurrence in Human Temporal Lobe Epilepsy
title_sort increased immunoglobulin and proteoglycan synthesis in resected hippocampal tissue predicts post surgical seizure recurrence in human temporal lobe epilepsy
topic temporal lobe epilepsy
surgery outcome
autoantibodies
neuroinflammation
transcriptome
temporal lobectomy
url https://www.mdpi.com/1873-149X/32/2/15
work_keys_str_mv AT michaelfhammer increasedimmunoglobulinandproteoglycansynthesisinresectedhippocampaltissuepredictspostsurgicalseizurerecurrenceinhumantemporallobeepilepsy
AT martineweinand increasedimmunoglobulinandproteoglycansynthesisinresectedhippocampaltissuepredictspostsurgicalseizurerecurrenceinhumantemporallobeepilepsy