TY - JOUR
T1 - Proteomics and Transcriptomics of the Hippocampus and Cortex in SUDEP and High-Risk SUDEP Patients
AU - Leitner, Dominique F.
AU - Mills, James D.
AU - Pires, Geoffrey
AU - Faustin, Arline
AU - Drummond, Eleanor
AU - Kanshin, Evgeny
AU - Nayak, Shruti
AU - Askenazi, Manor
AU - Verducci, Chloe
AU - Chen, Bei Jun
AU - Janitz, Michael
AU - Anink, Jasper J.
AU - Baayen, Johannes C.
AU - Idema, Sander
AU - van Vliet, Erwin A.
AU - Devore, Sasha
AU - Friedman, Daniel
AU - Diehl, Beate
AU - Scott, Catherine
AU - Thijs, Roland
AU - Wisniewski, Thomas
AU - Ueberheide, Beatrix
AU - Thom, Maria
AU - Aronica, Eleonora
AU - Devinsky, Orrin
N1 - Publisher Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. Copyright: This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
PY - 2021/5/25
Y1 - 2021/5/25
N2 - OBJECTIVE: To identify the molecular signaling pathways underlying sudden unexpected death in epilepsy (SUDEP) and high-risk SUDEP compared to control patients with epilepsy. METHODS: For proteomics analyses, we evaluated the hippocampus and frontal cortex from microdissected postmortem brain tissue of 12 patients with SUDEP and 14 with non-SUDEP epilepsy. For transcriptomics analyses, we evaluated hippocampus and temporal cortex surgical brain tissue from patients with mesial temporal lobe epilepsy: 6 low-risk and 8 high-risk SUDEP as determined by a short (<50 seconds) or prolonged (≥50 seconds) postictal generalized EEG suppression (PGES) that may indicate severely depressed brain activity impairing respiration, arousal, and protective reflexes. RESULTS: In autopsy hippocampus and cortex, we observed no proteomic differences between patients with SUDEP and those with non-SUDEP epilepsy, contrasting with our previously reported robust differences between epilepsy and controls without epilepsy. Transcriptomics in hippocampus and cortex from patients with surgical epilepsy segregated by PGES identified 55 differentially expressed genes (37 protein-coding, 15 long noncoding RNAs, 3 pending) in hippocampus. CONCLUSION: The SUDEP proteome and high-risk SUDEP transcriptome were similar to those in other patients with epilepsy in hippocampus and cortex, consistent with diverse epilepsy syndromes and comorbid conditions associated with SUDEP. Studies with larger cohorts and different epilepsy syndromes, as well as additional anatomic regions, may identify molecular mechanisms of SUDEP.
AB - OBJECTIVE: To identify the molecular signaling pathways underlying sudden unexpected death in epilepsy (SUDEP) and high-risk SUDEP compared to control patients with epilepsy. METHODS: For proteomics analyses, we evaluated the hippocampus and frontal cortex from microdissected postmortem brain tissue of 12 patients with SUDEP and 14 with non-SUDEP epilepsy. For transcriptomics analyses, we evaluated hippocampus and temporal cortex surgical brain tissue from patients with mesial temporal lobe epilepsy: 6 low-risk and 8 high-risk SUDEP as determined by a short (<50 seconds) or prolonged (≥50 seconds) postictal generalized EEG suppression (PGES) that may indicate severely depressed brain activity impairing respiration, arousal, and protective reflexes. RESULTS: In autopsy hippocampus and cortex, we observed no proteomic differences between patients with SUDEP and those with non-SUDEP epilepsy, contrasting with our previously reported robust differences between epilepsy and controls without epilepsy. Transcriptomics in hippocampus and cortex from patients with surgical epilepsy segregated by PGES identified 55 differentially expressed genes (37 protein-coding, 15 long noncoding RNAs, 3 pending) in hippocampus. CONCLUSION: The SUDEP proteome and high-risk SUDEP transcriptome were similar to those in other patients with epilepsy in hippocampus and cortex, consistent with diverse epilepsy syndromes and comorbid conditions associated with SUDEP. Studies with larger cohorts and different epilepsy syndromes, as well as additional anatomic regions, may identify molecular mechanisms of SUDEP.
UR - http://www.scopus.com/inward/record.url?scp=85107091428&partnerID=8YFLogxK
U2 - https://doi.org/10.1212/WNL.0000000000011999
DO - https://doi.org/10.1212/WNL.0000000000011999
M3 - Article
C2 - 33910938
SN - 0028-3878
VL - 96
SP - e2639-e2652
JO - Neurology
JF - Neurology
IS - 21
ER -