Abstract Details

Title Analysis Of Differentially Expressed Genes By RNA-Sequencing In 38 Cases of Rasmussen Encephalitis: New Insights on Non-Inflammatory Pathways

Topic Child Neurology and Developmental Neurology

Presentation(s) P12 - Poster Session 12 (5:30 PM-6:30 PM)

Poster/Presentation
Number 4-002

Objective To analyze aberrant gene expression pathways involved in the pathophysiology of Rasmussen Encephalitis (RE) in a large cohort of brain specimens from affected children.

Background RE is a rare cause of pharmacoresistant epilepsy, characterized by progressive hemispheric inflammation resulting in seizures and, if left untreated, hemiplegia, hemianopia and cognitive decline. Data on gene expression in this condition are lacking.

Design/Methods We conducted RNA-sequencing of flash-frozen resected epileptogenic tissue from 38 children with RE. Control brain tissue included 10 brain specimens from perilesional resected areas in different patients with focal cortical dysplasia. RNA-sequencing was performed using standard protocol on Illumina HiSeq 2x150bp sequencing, single index platform with polyA selection library prep. After extraction of normalized gene hit counts, we utilized the DESeq2 package with R version 4.2.1. The Wald test was used to generate p-values and log2 fold changes. Genes with an adjusted p-value < 0.05 were called as differentially expressed genes (DEG) for each comparison. Gene enrichment analysis was then performed with the Reactome platform.

Results We identified 6184 upregulated and 3789 downregulated genes in RE vs. controls. Functional gene clustering analysis showed overrepresentation of several pathways involved in neuroinflammation including interferon alpha/beta (p=7.77E-11) and gamma (p=1.17E-12) signaling, IL-4/IL-13 (p=1.15E-2), IL-10 (p=2.18E-2) signaling, class I MHC-mediated antigen processing (p=4.22E-5), and non-inflammatory pathways such as nonsense-mediated RNA decay (p=2.04E-3), translation elongation cycle (p=5.42E-4). We observed downregulation of multiple neuronal pathways: neurotransmitter receptors and postsynaptic signal transmission (p=3.79E-7), activation of NMDA receptors (p=1.72E-5), GABA receptor activation (p=3.19E-2), glutamate binding (p=2.1E-2), presynaptic depolarization and Ca channel opening (p=1.49E-2). Extra-neuronal downregulated genes included: transcriptional regulation of MECP2 (p=4.49E-4), L1CAM interactions (p=1.51E-3), signaling by NTRKs (p=3.93E-2), calmodulin pathway (p=2.05E-1).

Conclusions With this study, we contribute to expanding the knowledge of pathophysiological inflammatory and non-inflammatory processes involved in Rasmussen’s encephalitis.

Authors/Disclosures
Luca Bartolini, MD, FAAN (Meyer Children's Hospital) PRESENTER	Dr. Bartolini has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Vertex Pharmaceuticals. Dr. Bartolini has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for ��ɫ��.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
William D. Gaillard, MD (Children'S National Hospital)	The institution of Dr. Gaillard has received research support from all federal or foundation grants, NINDS, NIDCD, NICHD, NSF ,PERF.
	No disclosure on file
	No disclosure on file
Judy Liu, MD, PhD (Brown University)	The institution of Dr. Liu has received research support from NIH/NINDS.

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