Microstructural Abnormalities of the Amygdala in Focal Epilepsy with Varied Levels of SUDEP Risk Revealed by Advanced Diffusion MRI
Abstract number :
1.244
Submission category :
5. Neuro Imaging / 5A. Structural Imaging
Year :
2021
Submission ID :
1826156
Source :
www.aesnet.org
Presentation date :
12/4/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:52 AM
Authors :
Antoine Legouhy, PhD - University College London Institute of Neurology, London, UK; Luke A. Allen - Department of Clinical and Experimental Epilepsy - University College London Institute of Neurology, London, UK; Sjoerd B. Vos - Centre for Medical Image Computing - University College London, London, UK; Gavin P. Winston - Department of Clinical and Experimental Epilepsy - University College London Institute of Neurology, London, UK; John S. Duncan - Department of Clinical and Experimental Epilepsy - University College London Institute of Neurology, London, UK; Joana Oliveira - Department of Clinical and Experimental Epilepsy - University College London Institute of Neurology, London, UK; Catherine Scott - Department of Clinical and Experimental Epilepsy - University College London Institute of Neurology, London, UK; Rajesh Kumar - Brain Research Institute, University of California, Los Angeles, Los Angeles, California; Samden D. Lhatoo - Department of Neurology, - University of Texas Health Sciences Center at Houston, United States; Jennifer A Ogren - Department of Neurobiology - David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California; Michalis Kassinopoulos - Department of Clinical and Experimental Epilepsy - University College London Institute of Neurology, London, UK; Ronald M. Harper - Brain Research Institute, University of California, Los Angeles, Los Angeles, California; Hui Zhang - Centre for Medical Image Computing - University College London, London, UK; Beate Diehl - Department of Clinical and Experimental Epilepsy, - University College London Institute of Neurology, London, UK
Rationale: Although mechanisms underlying sudden unexpected death in epilepsy (SUDEP) remain unclear, monitored SUDEP cases highlighted a fatal sequence of transient apnea, sinus pauses leading to terminal apnea followed by asystole. All followed generalized tonic-clonic seizures (GTCS), the frequency of which are a major risk factor.
MRI studies show volume changes in people considered at risk of SUDEP and those who succumbed to it in cardiorespiratory brain sites. Specifically, increased amygdala volumes, with decreases elsewhere (Allen et al., 2019). The amygdala is influential in triggering apnea, as shown in animal and human studies, including direct electrical stimulation of the structure (Rhone et al., 2020).
The nature of the volume changes, and their consequences to amygdala dysfunction are unclear. To determine the microstructure of the amygdala in people with focal epilepsy with and without GTCS reflecting various SUDEP risk and healthy control subjects, we used metrics provided by diffusion tensor imaging (DTI), and neurite orientation dispersion and density imaging (NODDI). NODDI enables differentiation of two important aspects of neuronal morphology: the packing density of neurites (neurite density index [NDI]) and the spatial organization of these neuronal projections (orientation dispersion index [ODI]).
Methods: As part of a prospective study on autonomic and imaging biomarkers of SUDEP, 156 patients with focal epilepsy underwent video EEG, polygraphic and MRI acquisitions on a 3T scan, including anatomical (T1-weighted) and multi-shell diffusion weighted images (DWI) enabling DTI and NODDI. After outlier rejection, a total of 109 patients and 53 healthy controls were considered for the analysis, divided into groups based on GTCS presence and frequency, and frequency of focal seizures.
After correction for head motion and common artifacts, DWI volumes were used to estimate DTI metrics (mean diffusivity (MD) and fractional anisotropy (FA)) and NODDI metrics (NDI and ODI). Amygdala segmentations were performed on T1 images using Freesurfer.
Analysis of covariance (ANCOVA) was used to assess differences between GTCS groups on the diffusion metrics after correcting for the influence of sex and age. In case of significance, post-hoc pairwise t-tests were performed to compare each group to the others. Multiple comparison was handled using Bonferroni correction with 5% FWER.
Results: Significant differences were found in the amygdala bilaterally, on the NDI metric especially. The subsequent pairwise t-tests showed that the differences were between the healthy control group and all the epilepsy groups. No significant differences were found between the epilepsy groups.
Conclusions: A measure of architectural complexity of dendrites and axons, collectively termed neurites, as well as connections are reduced in the amygdala of people with epilepsy relative to healthy controls. The amygdala architecture is complex, serving multiple roles in integrating input from the insula, frontal cortex, and other areas, and processing those inputs to influence brainstem breathing and blood pressure final pathways.
Funding: Please list any funding that was received in support of this abstract.: National Institute of Neurological Disorders and Stroke, Grant: U01-NS090407.
Neuro Imaging