Objective
The diagnosis of acute ischemic stroke (AIS) is time-sensitive and reliant on neuroimaging, which is not always immediately accessible. This systematic review aims to identify and evaluate bloodbased biomarkers with potential to support early diagnostic decision-making and facilitate prompt referral for confirmatory imaging and treatment.
Methods
Following the PRISMA guidelines, a systematic search of PubMed, Web of Science, LILACS, Medline, Scopus, Scielo, Epistemonikos and TRIP Data Base was conducted for primary studies published in the last five years. Original studies evaluating blood-based biomarkers collected within 12 hours of symptom onset for early diagnosis of AIS were included. The methodological quality of included studies was assessed using the QUADAS-2 tool.
Results
Ten studies met the inclusion criteria, investigating a range of biomarkers including proteins, non-coding RNAs, and lipids. Most studies were case-control in design, with overall risk of bias rated as low to moderate. Multi-marker panels combining biomarkers with clinical scales (e.g., D-dimer and GFAP with FAST-ED; AUC = 0.95), and lipidomics-based models (AUC = 0.968), demonstrated the highest diagnostic performance. Several individual non-coding RNAs also showed promising accuracy (AUC > 0.85).
Conclusion
Blood-based biomarkers, especially when used in multi-marker panels, demonstrate considerable potential as triage tools for early AIS diagnosis. Their application in point-of-care settings could reduce diagnostic uncertainty and accelerate time to treatment. However, prospective validation in real-world emergency environments is essential prior to clinical implementation.
