Abstract DP220: Neuroinflammatory Cascade in First 24 Hours after Acute Ischemic Stroke Predicts Early Outcome: Circulating Inflammatory Factors Obtained on a Mobile Stroke Unit

Background: Neuroinflammation after acute ischemic stroke (AIS) is well known, but is largely untreated. The impact on outcome from the inflammatory cascade arising at stroke onset and progressing over 24 hours has not been previously described. We measured inflammatory factors in blood from patients on a mobile stroke unit (MSU) and over 24 hours and evaluated their association with outcome. Methods: The study is a prospective, cohort investigation of inflammatory factors in plasma obtained on an MSU, during hospitalization, and from adult controls. Nine cytokines were measured with electrochemiluminescence: IL-6, IFN-γ, IL-10, IL-12p70, IL-17, IL-1β, IL-2, IL-4, and TNF-α. Demographics, stroke severity, lesion volume, thrombolysis and thrombectomy were analyzed. Outcome measures were mRS and NIHSS at hospital discharge. Results: The study evaluated 95 adults; 70 patients treated on the MSU between August 2021 and June 2025, and 25 controls. Forty-one (59%) MSU patients with confirmed AIS were included in the analysis. Median age was 69 (range 36-94) years, 46% were female, and 71% white. Median initial NIHSS score was 7 (range 1-28). Median lesion volume on MRI was 2.2 (range 0-171) mL. Thirty-three (80%) patients received IV thrombolysis and 10 (24%) had mechanical thrombectomy. Blood was obtained a median of 68 minutes after symptom onset and at 24.9 hours. At hospital discharge 19 (46%) patients had favorable functional status (mRS 0-1) and 27 (73%) milder stroke deficits (NIHSS score 0-4). Older age was associated with poorer mRS. All cytokines were abnormal within 26 minutes of symptom onset, and at 24 hours all were higher in patients with poorer mRS and NIHSS. Most pronounced for mRS were IL-6 (median 7.5 pg/mL favorable vs. 29.0 pg/mL unfavorable, p=0.002), IL-2 (median 93 fg/mL favorable vs. 193 fg/mL unfavorable, p=0.032) and TNF-α (median 503 fg/mL favorable vs. 886 fg/mL unfavorable, p=0.001). Effects of these cytokines in discharge NIHSS were comparable. In multivariable analyses controlling for stroke severity and age, lower levels of IL-6 and TNF-α at 24 hours predicted better outcomes. Conclusions: In this sample of 41 adults with AIS, neuroinflammation was elevated within minutes after stroke onset, and a greater increase over the next 24 hours predicted worse functional outcomes and stroke deficits. The effect was most pronounced with IL-6, IL-2 and TNF-α. These findings suggest potential therapeutic targets for neuroinflammation in AIS.