Brain Temperature and Immune System Response in Temporal Lobe Epilepsy
Abstract number :
3.089
Submission category :
2. Translational Research / 2C. Biomarkers
Year :
2023
Submission ID :
654
Source :
www.aesnet.org
Presentation date :
12/4/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Christina Mueller, PhD – University of Alabama at Birmingham Heersink School of Medicine
Ayushe Sharma, PhD – University of Alabama at Birmingham Heersink School of Medicine; Hongwei Qin, PhD – University of Alabama at Birmingham Heersink School of Medicine; Huixian Hong, MD, PhD – University of Alabama at Birmingham Heersink School of Medicine; Etty Benveniste, PhD – University of Alabama at Birmingham Heersink School of Medicine; Jerzy Szaflarski, MD, PhD – Neurology – University of Alabama at Birmingham Heersink School of Medicine
Rationale: Studies have shown that neuroinflammation contributes to neuronal hyperexcitability, glial activation, and network plasticity and is a primary contributor to seizure initiation and maintenance in temporal lobe epilepsy (TLE). Developing non-invasive procedures to measure neuroinflammation has been a major focus of neuroimaging investigations in epilepsy. Such a technique would allow visualization of abnormal brain regions for possible surgical resection and monitoring of disease course and treatment responses. It could also help determine why some patients fail to reach remission with anti-epileptic medications. We used whole-brain magnetic resonance spectroscopic imaging (MRSI) to quantify brain temperature as a non-invasive proxy of neuroinflammation in TLE. Our guiding hypothesis was that neuroinflammation is increased in the temporal lobes of TLE patients compared to healthy controls (HCs), as quantified with MRSI-derived brain temperature.
Methods: Eighteen TLE patients and 18 age-matched HCs underwent MRSI and TLE patients provided blood samples. The Metabolite Imaging and Data Analysis System (MIDAS) was used to derive voxel-level brain temperature. Ten TLE patients had ictal onset in the right temporal lobe. To enable group comparisons, temperature maps for patients with left-sided seizure onset (n=8) were flipped so that all ictal onset zones were on the right (ipsilateral to seizure onset side). Brain temperature in the temporal lobes was compared between groups using AFNI’s 3dttest++. We also assessed associations between increased brain temperature and peripheral biomarkers of inflammation (pro-inflammatory cytokines and chemokines). Plasma was obtained from whole blood and pro-inflammatory cytokines and chemokines (interferon [IFN]-γ, interleukin [IL]-1β, IL-6, IL-17A, monocyte chemoattractant protein [MCP]-1, macrophage inflammatory protein [MIP]-1α and MIP-1β, and tumor necrosis factor [TNF]-α) were quantified with multiplex assays. Pearson correlation coefficients were obtained between brain temperature and the cytokines and chemokines.
Results: Brain temperature was increased in ipsilateral temporal pole and middle and inferior temporal gyri (cluster 1) and in the contralateral temporal pole, middle and inferior temporal gyri, parahippocampal gyrus, and fusiform (cluster 2). Increased temperature in cluster 1 was associated with higher IL-1β (r=0.489, p=0.040), IL-17A (r=0.528, p=0.024), and TNF-α (r=0.679, p=0.002), and increased temperature in cluster 2 (contralateral to seizure onset) was associated with higher IL-1β (r=0.479, p=0.044) and TNF-α (r=0.505, p=0.032).
Conclusions: We report temperature increases in the bilateral temporal lobes of TLE patients that were associated with pro-inflammatory cytokines and chemokines in plasma, supporting the idea that MRSI-derived brain temperature could be used to visualize neuroinflammatory responses in TLE and that this technique could be further developed to pinpoint seizure onset zones characterized by abnormal localized inflammatory responses.
Funding: University of Alabama at Birmingham Heersink School of Medicine’s AMC21 program, State of AL General Fund, and the UAB Epilepsy Center
Translational Research