Abstract Details

Title Transcriptomic Analysis Identifies a Signature of Metabolic–Immune Polarity in Focal Cortical Dysplasia Type IIa

Topic Epilepsy/Clinical Neurophysiology (EEG)

Presentation(s) S29 - Epilepsy: Basic Science and Mechanisms (3:42 PM-3:54 PM)

Poster/Presentation
Number 002

Objective To characterize the transcriptomic profile of focal cortical dysplasia (FCD) type IIa and explore the interplay between metabolic, neuroinflammatory, and vascular pathways contributing to intrinsic epileptogenicity.

Background FCDIIa is a developmental malformation characterized by cortical lamination defects and dysmorphic neurons, and represents a leading cause of drug-resistant epilepsy. Inflammatory mechanisms have been proposed to contribute to epileptogenesis, but the molecular landscape of histologically pure FCD IIa remains poorly defined.

Design/Methods Bulk RNA-seq counts (GSE213488) from surgically resected human FCD IIa and control gray-matter cortex were analyzed using iDEP2. Low-abundance genes were filtered (CPM > 0.5 in ≥1 sample) and normalized (log2-CPM). Differential expression was performed using DESeq2 (FDR < 0.05, |log2FC| ≥ 1). Functional interpretation was conducted through over-representation analysis (ORA) of significant DEGs and preranked gene set enrichment analysis (fgsea) across Gene Ontology, Hallmark, KEGG, and Curated.Reactome databases (FDR < 0.05).

Results Differential expression identified 85 upregulated and 130 downregulated genes defining a distinctive molecular polarity. Upregulated genes converged on oxidative phosphorylation, cholesterol biosynthesis, and synaptic vesicle cycling, indicating heightened neuronal and astrocytic metabolic drive. Conversely, downregulated programs encompassed interferon and IL-6–JAK–STAT3 signaling, complement cascade, endothelial adhesion, and angiogenesis, suggesting suppression of immune–vascular communication. GSEA corroborated these patterns, showing strong enrichment of Oxidative Phosphorylation and Synaptic Transmission (NES > 2.0, FDR < 0.01) alongside coordinated depletion of IL6–JAK–STAT3, Interferon-α/γ, Complement, and Angiogenic pathways (NES < –2.0, FDR < 0.01), together delineating an energetically active yet immunologically dormant cortical network.

Conclusions The transcriptomic signature of FCD IIa indicates a state of metabolic-immune polarity: metabolically active yet immunologically and vascularly subdued cortical state. This "metabolic isolation" may create a self-sustaining hyperexcitable circuit that evades normal homeostatic regulation, contributing to pharmacoresistance. These findings reframe epileptogenesis in FCD IIa as a disorder of metabolic–microenvironmental imbalance.

Authors/Disclosures
Ahmad Saeed, MD (The University of Jordan) PRESENTER	Mr. Saeed has nothing to disclose.
Osama M. Younis, MD	Dr. Younis has nothing to disclose.
Hazim M. Aldweik, MD (Jordan University Hospital)	Dr. Aldweik has nothing to disclose.
Haneen Alsha'ar (University of Jordan)	Ms. Alsha'ar has nothing to disclose.
Eman M. Hassan, MD	Dr. Hassan has nothing to disclose.
Majed S. Hbahbih, MD	Dr. Hbahbih has nothing to disclose.

��ɫ��

��ɫ��