Abstract
The preferred treatment for acute ischaemic stroke (AIS) is intravenous thrombolysis (IVT) administered within 4.5 hours (h) of symptom onset. This study aimed to identify metabolomic biomarkers for distinguishing AIS patients within 4.5 h of symptom onset, addressing the often exclusion of those with unknown onset times from IVT. In this retrospective case-control study with 30 AIS patients, early AIS with onset time within 0-4.5 h (ES, n = 16) and late AIS within 4.5-24 h (LS, n = 14) groups were differentiated. Their complete sets of plasma metabolites were examined. A stepwise analysis was performed to identify potential biomarkers. Biliverdin and Nicotinamide N-oxide (NAMO) emerged as potential biomarkers, combined to achieve a high AUC of 0.964 (95% Confidential interval 0.900-1), a specificity of 100% (78.47-100%), and a sensitivity of 93.75% (71.67-98.89%) for AIS onset time determination. These metabolites show promise as molecular clocks for determining the onset time of AIS, potentially extending IVT access to patients with unknown onset times. However, their clinical applicability necessitates rigorous validation in larger and independent cohorts to establish their role in improving AIS management through extended IVT accessibility.