Abstract Body: Background: Rehabilitation therapy is an important component of acute ischemic stroke (AIS) recovery. A major hinderance is the inability to predict which patients benefit from mobilization during the first 24 hours (ERehab). We hypothesize serum biomarker analyses during the hyperacute phase can bridge the gap.

Methods: This is a single center study of 20 AIS patients & 14 age/sex matched controls enrolled from 3/2022-6/2023. Serum samples were collected at 4 time points – angiography suite before cerebral reperfusion or Neuro ICU at hospital admission, 12, 24 & 72 hours. Biomarker candidates were identified using a DisGeNET search for AIS associated proteins; 70% achieved an Evidence Index cutoff score of 1, indicating all publications support human gene-disease or variant-disease associations. Time course of serum proteome changes was evaluated using aptamer-based SomaScan assay, measuring 1500 proteins. NIH Database for Annotation, Visualization & Integrated Discovery (DAVID) Gene Functional Classification Tool compared shared genes and biomarkers for stroke (vs healthy controls) & unfavorable (vs favorable) outcome, characterized by modified Rankin Scale (mRS) score of 3-6 (vs 0-2), at hospital discharge & 90 days (90d).

Results: The mean age of AIS patients was 59 years, 65% were male. Median NIHSS score was 11, Charlson Comorbidity Index score was 5.5 and the median last known well to hospital admission was 6.6 hrs. The average time to first mobilization was 39 hrs, 25% received ERehab. The mean rehab duration during AIS hospitalization was 438 min; median length of stay was 8.4 days, 40% received post-acute rehabilitation. Median AIS volume was 36mL, 65% of patients had ICA or M1/MCA involvement. Approximately 65% received IV thrombolysis, 80% underwent cerebral reperfusion therapy, 94% achieved modified thrombolysis in Cerebral Infarction score ≥ 2b. The median mRS was 4 at hospital discharge, 3 at 90d. Mortality rate was 10%. DAVID analyses resulted in 22 biomarkers at hospital discharge & 35 biomarkers at 90d associated with favorable outcome. Gene expression differences were present at each time point (Figure).

Conclusions: We identified multiple serum biomarkers and gene clusters associated with favorable outcomes at hospital discharge and 90d in AIS patients, indicating a need for several biologic targets to predict ERehab response during the hyperacute phase. These findings provide an early framework for tailored stroke recovery interventions.