Date of Award

January 2026

Document Type

Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Nishant K. Mishra

Abstract

Hemorrhagic strokes, specifically intracerebral hemorrhages (ICH), can be complicated by post-stroke seizures (PSS), a condition that can worsen patient outcomes. Emerging research indicates that inflammatory biomarkers play a role in the development of epilepsy (epileptogenesis) and mortality. I conducted a retrospective cohort study to determine whether plasma levels of biomarkers (CCL2, IL6, CXCL8 (IL8), GCSF, IL1β, MIP-1a, TNF-a, and IL10) could serve as prognostic indicators for post stroke outcomes (PSS, mortality, and poor outcomes at 90-, 180-, and 365-days post-ICH). Our hypotheses are that increased level of inflammatory biomarkers will lead to higher risk of developing seizures or epileptiform discharge on EEG, while those primarily known for anti-inflammatory properties will lead to decreased risk of developing seizures or epileptiform discharges on EEG. I collated ICH data from the Acute Brain Injury Repository (Yale New Haven Hospital) from 2014 to 2021. Plasma biomarker levels were measured via cytometric bead array. Patients with EEG-recorded epileptiform discharges, EEG-recorded seizures, or clinical seizures after ICH were defined as seizures and epileptiform discharges (SED), while those without were defined as non-SED. SED was further classified into early and late, occurring before and 7 days post-ICH, respectively. Additionally, we examined if biomarkers were associated with poor outcome (modified Rankin Scale [mRS] score of 3 to 6) and mortality at 90-, 180-, and 365-days post-ICH. We conducted univariable and multivariable logistic regression analyses and reported the findings as Odds Ratio (OR) and 95% CI. We examined 172 patients with ICH, of whom 33 had early SED, 29 had late SED, and 110 had no SED. In univariable analyses, CCL2, ICH volume, diabetes, and lobar ICH were significantly associated with late SED, whereas NIHSS score at admission, ICH volume, and lobar ICH were significantly associated with early SED (p<0.05). Lower CCL2 levels were independent predictors of late SED in multivariable analyses (OR 0.61; 95% CI 0.45-0.81, p<0.001), but not of early SED. Additionally, we identified an independent association between higher CCL2 levels and 90-day mortality in multivariable analysis for the combined early and late SED cohorts (OR 1.87; 95% CI 1.03-3.37, p=0.038). Our results, despite limitations, provide greater insight into the effects of CCL2 on PSS and outcomes after ICH, impacting prognostication and therapeutic-building potential, which may improve patient health outcomes and improved quality-of-life. Longitudinal studies examining PSS after ICH are required, especially with large patient samples and long-term follow-up, to further elucidate the mechanisms behind CCL2 function.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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