Prognostication of Outcomes in Stroke Patients Using Inflammatory Biomarkers: Findings from the Yale Post-stroke Epilepsy Research Group
Ethan Wang1, Shubham Misra1, Jennifer Yan1, Pei Yi Chook2, Yuki Kawamura3, Rachel Kitagawa1, Jennifer A. Kim1, Emily J. Gilmore1, Adam De Havenon1, Adithya Sivaraju1, Lawrence J. Hirsch1, Guido Falcone1, Lauren H. Sansing1, Jessica Magid-Bernstein1, Nishant Mishra1
1Yale University, 2Universiti Malaya, 3University of Cambridge
Objective:

To characterize the predictive value of inflammatory plasma biomarkers in post-stroke seizures (PSS) risk and functional outcomes in PSS risk patients at 1-year follow-up.

Background:

PSS are complications of intracerebral hemorrhage (ICH) linked to adverse outcomes. Animal data suggest that post-stroke inflammation contributes to epileptogenesis.

Design/Methods:

We reviewed 2015-2021 Yale New Haven Hospital ICH patients' records to collate data. A cytometric bead array determined plasma biomarker levels. We defined PSS risk as clinical seizures or EEG-recorded epileptiform discharges post-stroke and poor outcomes as Rankin scale score 3-6. We used logistic regression to analyze the association between inflammatory biomarkers, clinical variables, PSS risk, and the association of inflammatory biomarkers with poor outcomes at 1-year follow-up. We report Odds Ratio (OR) and 95% Confidence Interval (CI) for our analyses.

Results:

We included 178 ICH patients, 66 with PSS risk (49% males, age 68 (48-88)) and 112 without (60% males, age 68 (59.5-76.5)), without differences in NIHSS (p=0.2). Hypertension, diabetes, antiplatelet use, deep ICH, and C-C motif chemokine ligand-2 (CCL2) were associated with decreased PSS risk. In contrast, prior TIA, lobar ICH, and ICH volume were associated with increased PSS risk in univariable analyses. Diabetes was a protective factor (OR 0.4; CI: 0.1–0.9), whereas lobar ICH (OR 6.8; CI: 3.4–13.4) was significantly associated with PSS risk in multivariable analyses. Older age, female sex, obesity, hypertension, higher ICH score and ICH volume, higher NIHSS, antihypertensive medications, and lower hemoglobin and CCL2 levels were associated with poor outcomes in univariable analyses. Lower CCL2 levels (OR 0.99; CI 0.97-0.99) were significantly associated with poor outcomes in multivariable analyses.

Conclusions:

In our retrospective analyses, lower CCL2 levels predicted poor outcomes at 1-year post-stroke. No inflammatory biomarker was associated with PSS risk in this cohort. Prospective studies investigating the temporal profile of inflammatory biomarkers with PSS risk are needed.

10.1212/WNL.0000000000204783