Peripheral Immune System Activity in Temporal Lobe Epilepsy Correlates with NODDI Multi-Compartment
Poster No:
78
Submission Type:
Abstract Submission
Authors:
Jerzy Szaflarski1, Rodolphe Nenert1, Huixian Hong1, Christina Mueller1, Ayushe Sharma2, Hongwei Qin1, Etty Benveniste1
Institutions:
1University of Alabama at Birmingham, Birmingham, AL, 2Yale University, New Haven, CT
First Author:
Co-Author(s):
Introduction:
Studies of patients with temporal lobe (TLE) and other focal onset epilepsies have shown that neuroinflammation is a contributor to seizure initiation and maintenance. We have recently shown a correlation between peripheral molecular and cellular biomarkers of inflammation and focal increase in temperature in the temporal lobe ipsilateral to seizure onset (i.e., the affected temporal lobe; aTL) in patients with treatment-resistant TLE (Mueller et al., 2024 Epilepsia Open). Here, we use whole-brain diffusion magnetic resonance imaging to identify abnormalities in multicompartment Neurite Orientation Dispersion and Density Imaging (NODDI) measures (FISO (free water), FICVF (neurite density), and ODI (neurite dispersion)) as a non-invasive proxy of neuroinflammation in TLE and examine the relationship between these measures and molecular and cellular biomarkers of peripheral inflammation in TLE. We hypothesize that FISO, FICVF, and ODI changes in the ictal onset zone (aTL) will be associated with these biomarkers.
Methods:
Eighteen patients with scalp video/EEG confirmed TLE and 18 age-matched healthy controls (HCs) underwent 3T MRI high angular resolution diffusion imaging (HARDI) protocol. NODDI FISO, FICVF and ODI statistical maps were generated for each participant. Two-sample t-tests (FDR corrected, p<0.05) were conducted to compare the two groups across these maps, focusing on the temporal region using a previously published binary mask (Sharma et al., 2023 Epilepsia). Peripheral venous blood was collected within <1 hour of imaging for extensive exploratory cellular and molecular biomarker testing. For each significant cluster identified, FISO, FICVF and ODI values were extracted for the TLE group and correlated with the biomarkers of peripheral inflammation.
Results:
Mostly in the aTL, we observed significantly lower FICVF values compared to HCs indicating the expected neurite loss in the affected by epilepsy temporal lobe (Figure). These neurite density losses correlated with several molecular and cellular biomarkers (Table; e.g., granulocyte colony-stimulating factor (G-CSF) suggestive of decreased anti-inflammatory reaction, and vascular endothelial growth factor A (VEGF-A) indicating lower suppression of new vessel formation in aTL) or cellular biomarkers (e.g., decreased association with Breg indicating lower immunomodulation in aTL). We also observed higher ODI and FISO values in the aTL compared to HCs (Figure). Increased ODI and FISO indicate changes in tissue microstructure such as higher dendritic branching and increased extracellular water content, which are the key aspects of neuroinflammation. These changes significantly correlated with numerous molecular and cellular peripheral biomarkers of inflammation (Table). For example, there were positive associations in the aTL with several chemokines responsible for regulating immune responses. However, we also observed a decreased association with IL-6 known to stimulate acute immune responses and be elevated in treatment-resistant TLE. Cellular responses also positively correlated with the structural changes indicating increased peripheral cellular response to aTL inflammatory microstructural changes (or to seizure-induced damage).
Conclusions:
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 monitoring of disease course and treatment response. NODDI differences between TLE and HCs mostly localized to the aTL indicate a specific relationship between imaging biomarker of injury/neuroinflammation and cellular/molecular biomarkers of inflammation and support NODDI as a possible measure of neuroinflammation in TLE.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Novel Imaging Acquisition Methods:
Diffusion MRI 2
Physiology, Metabolism and Neurotransmission:
Physiology, Metabolism and Neurotransmission Other
Keywords:
Epilepsy
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
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·Table
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Sharma AA, Nenert R, Goodman AM, Szaflarski JP “Concordance between focal brain temperature elevations and focal edema in temporal lobe epilepsy” Epilepsia 2023, May; 64(5):1289-1304; PMID 36762949