Proteomics and Transcriptomics of the Hippocampus and Cortex in SUDEP and High-Risk SUDEP Patients

To identify the molecular signaling pathways underlying sudden unexpected
death in epilepsy (SUDEP) and high-risk SUDEP compared to control patients
with epilepsy. 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. 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. 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.