Proteomic Signatures of Patients with Post-Ischemic Stroke Seizures
Patrick Ellsworth1, Nishant Mishra3, Guido Falcone4, Hongyu Zhao3, Srikant Rangaraju2, Richa Sharma2
1Department of Neurology, Yale University School of Medicine, 2Yale University School of Medicine, 3Yale University, 4Yale School of Medicine
Objective:
To characterize the protein expression profiles of patients with acute ischemic stroke (AIS) who subsequently have a post-stroke seizure.
Background:

Post-stroke seizure can be a disabling complication.

Design/Methods:
We conducted a proteomic study nested withing the Yale Longitudinal Study of Acute Brain Injury, an ongoing prospective study at our institution. We measured 11,000 proteins using the SomaScan 11K Assay. T-tests were performed to compare the abundance of each protein among patients with and without post-stroke clinical seizure prompting treatment. Proteins with an absolute value of maximum cross-fold change > 1.6 and a false-detection rate-adjusted p-value < 0.05 were retained. We performed a pathway analysis using the Reactome Pathways 2024 model. 
Results:
Plasma samples were collected for 64 patients with AIS (median time from LKN to sample collection 28.4 hours [22.5-67.8]). 4 had a diagnosis of a post-stroke seizure (median age 56y, all male, 50% White, 50% Black; 1 PH2 hemorrhagic transformation; 2 at post-stroke day, 1 at month 6 and 1 at month 7 post-stroke; 1 with electrographic seizure, 2 with lateralized periodic discharges, 1 with spike-wave complex). Patients with post-stroke seizure were younger (median age 56 versus 71 years), had higher NIHSS (median 14.5 versus 5.0), and more likely to receive anticoagulation (75% versus 32%). We identified 170 proteins significantly different between patients with and without post-stroke seizures. The top 4 proteins with the greatest fold change (4- to 7.2-fold) were: paired immunoglobulin-like type 2 receptor alpha isoform FDF02-deltaTM, T-complex protein 1 subunit eta, protein DDI1 homolog 2, adenylate kinase isoenzyme 1, and tubulin-specific chaperone cofactor E-like protein. Pathway analysis reveals differentially expressed proteins in the processes of cellular response to chemical stress, nucleotide excision repair, metabolism, and detoxification of reactive oxygen species. 
Conclusions:
In this exploratory analysis, patients with post-stroke seizures had differentially expressed proteins in the processes of cellular stress response.
10.1212/WNL.0000000000215796
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