A Status Epilepticus Network Linking Peri-Ictal MRI Abnormalities to Brain Metabolism, Receptor Density and Glutamate Signaling
Abstract number :
1.35
Submission category :
5. Neuro Imaging / 5B. Functional Imaging
Year :
2025
Submission ID :
957
Source :
www.aesnet.org
Presentation date :
12/6/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Joseph Turner, BS – Mass General Brigham/ NYU School of Medicine
Neal Nolan, MD – Brigham and Women's Hospital
Payam Damavandi, MD – Salzburg University
Ross MacFadyen, MS – Mass General Brigham
William Drew, BA – Mass General Brigham
Bassam Al-Fatly, MD, PhD – Charité – Universitätsmedizin Berlin
Clemens Neudorfer, MD – Mass General Brigham
Aaron Warren, PhD – Brigham and Women's Hospital, Harvard Medical School
Artemis Iatrou, PhD – Mass General Brigham
Urs Fisch, MD, PhD – Mass General Brigham
Samuel Snider, MD – Brigham and Women's Hospital, Harvard Medical School
Sattar Khoshkhoo, MD – Mass General Brigham, Harvard Medical School
John Rolston, MD, PhD – Brigham and Women's hospital, Harvard Medical School
Natalia Rost, MD, MPH – Mass General Brigham
Ona Wu, PhD – Mass General Brigham
Pilar Bosque-Varela, MD PhD – Christian Doppler University Hospital, Member of the European Reference Network EpiCARE, and Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria
Lukas Machegger, MD, PhD – Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria
Johannes Pfaff, MD – Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria
Marian Galovic, MD, PhD – University of Zurich
Andrew Cole, MD – Massachusetts General Hospital and Harvard Medical School
Jong Woo Lee, MD, PhD – Brigham and Women's Hospital, Harvard Medical School
Eugen Trinka, MD – Christian Doppler University Hospital, Member of the European Reference Network EpiCARE, and Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria
Michael Fox, MD, PhD – Mass General Brigham
Giorgi Kuchukhidze, MD, PhD – Salzburg University
Frederic Schaper, MD, PhD – Mass General Brigham
Rationale: Status epilepticus (SE) is a life-threatening condition characterized by prolonged or repeated seizures, often resistant to antiseizure medications, with unclear mechanisms and variable origins across the brain. Peri-ictal MRI abnormalities (PMAs) are common in SE and can provide clues to its implicated brain network. In this study, we use lesion network mapping to test whether SE-associated PMAs map to a shared brain network and evaluate their biological relevance.
Methods: We identified a discovery cohort of 92 published cases with SE-associated PMAs and mapped the brain network connected to each lesion using lesion network mapping (Boes, 2015 Brain). SE is a common stroke mimic and we therefore used stroke lesions (n=490) as controls. To identify common connections across SE-associated PMAs, we overlapped all lesion networks connected to PMAs and calculated the proportion of SE cases connected at each brain voxel (sensitivity map). To identify connections more strongly connected to PMA lesions than control lesions, we performed a voxelwise permutation t-test (specificity map). Regions both sensitive and specific to SE were defined by multiplying the sensitivity and specificity maps, resulting in an agreement map hereafter called an SE network. We tested the predictive validity of PMA overlap with this SE network in an independent validation cohort of 47 SE-associated PMAs and 120 control lesions from other etiologies (stroke, infection, tumor). We next assessed whether PMAs overlapped with maps of brain microstructure, metabolism, and receptor density derived from NeuroMaps (Markello, 2022 Nat Methods). These analyses were repeated in the validation cohort. Finally, we tested PMA overlap with gene expression maps from the Allen Human Brain Atlas (Hawrylycz, 2012 Nature).
Results: SE-associated PMAs were functionally connected to a shared brain network including the pulvinar, precuneus, claustrum, tectum, cerebellum and other limbic and default mode network areas. PMA overlap with the SE network predicted SE in the validation cohort with excellent accuracy (AUC=0.91, p< 0.001; sensitivity=0.83, specificity=0.90). Compared to control lesions, SE-associated PMAs localized to brain regions characterized by high synaptic and metabolic activity, including high cerebral blood flow, glucose metabolism, mitochondrial and receptor density (mGluR5, NMDA, GABAa, pFWE < 0.05), and low myelin content (pFWE< 0.05)
Neuro Imaging