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BMC Neurology

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Open Access 01-12-2024 | Epilepsy | Research article

Leukocyte differential gene expression prognostic value for high versus low seizure frequency in temporal lobe epilepsy

Authors: Ryan Sprissler, Michael Hammer, David Labiner, Neil Joshi, Albert Alan, Martin Weinand

Published in: BMC Neurology | Issue 1/2024

Abstract

Background

This study was performed to test the hypothesis that systemic leukocyte gene expression has prognostic value differentiating low from high seizure frequency refractory temporal lobe epilepsy (TLE).

Methods

A consecutive series of patients with refractory temporal lobe epilepsy was studied. Based on a median baseline seizure frequency of 2.0 seizures per month, low versus high seizure frequency was defined as ≤ 2 seizures/month and > 2 seizures/month, respectively. Systemic leukocyte gene expression was analyzed for prognostic value for TLE seizure frequency. All differentially expressed genes were analyzed, with Ingenuity® Pathway Analysis (IPA®) and Reactome, to identify leukocyte gene expression and biological pathways with prognostic value for seizure frequency.

Results

There were ten males and six females with a mean age of 39.4 years (range: 16 to 62 years, standard error of mean: 3.6 years). There were five patients in the high and eleven patients in the low seizure frequency cohorts, respectively. Based on a threshold of twofold change (p < 0.001, FC > 2.0, FDR < 0.05) and expression within at least two pathways from both Reactome and Ingenuity® Pathway Analysis (IPA®), 13 differentially expressed leukocyte genes were identified which were all over-expressed in the low when compared to the high seizure frequency groups, including NCF2, HMOX1, RHOB, FCGR2A, PRKCD, RAC2, TLR1, CHP1, TNFRSF1A, IFNGR1, LYN, MYD88, and CASP1. Similar analysis identified four differentially expressed genes which were all over-expressed in the high when compared to the low seizure frequency groups, including AK1, F2R, GNB5, and TYMS.

Conclusions

Low and high seizure frequency TLE are predicted by the respective upregulation and downregulation of specific leukocyte genes involved in canonical pathways of neuroinflammation, oxidative stress and lipid peroxidation, GABA (γ-aminobutyric acid) inhibition, and AMPA and NMDA receptor signaling. Furthermore, high seizure frequency-TLE is distinguished prognostically from low seizure frequency-TLE by differentially increased specific leukocyte gene expression involved in GABA inhibition and NMDA receptor signaling. High and low seizure frequency patients appear to represent two mechanistically different forms of temporal lobe epilepsy based on leukocyte gene expression.

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Title: Leukocyte differential gene expression prognostic value for high versus low seizure frequency in temporal lobe epilepsy
Authors: Ryan Sprissler
Michael Hammer
David Labiner
Neil Joshi
Albert Alan
Martin Weinand
Publication date: 01-12-2024
Publisher: BioMed Central
Keyword: Epilepsy
Published in: BMC Neurology / Issue 1/2024
Electronic ISSN: 1471-2377
DOI: https://doi.org/10.1186/s12883-023-03459-1

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Leukocyte differential gene expression prognostic value for high versus low seizure frequency in temporal lobe epilepsy

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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