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.

Objective
This study investigated the hospital diagnoses and characteristics of uncooperative prehospital patients suspected of acute stroke who could not undergo a prehospital stroke screening test (PHSST).
Methods
This retrospective observational study was conducted at a single academic hospital with a regional stroke center. We analyzed three scenario-based prehospital stroke screening performances using the final hospital diagnoses: (1) a conservative approach only in patients who underwent the PHSST, (2) a real-world approach that considered all uncooperative patients as screening positive, and (3) a contrapositive approach that all uncooperative patients were considered as negative.
Results
Of the 2,836 emergency medical services (EMS)-transported adult patients who met the prehospital criteria for suspicion of acute stroke, 486 (17.1%) were uncooperative, and 570 (20.1%) had a confirmed final diagnosis of acute stroke. The diagnosis in the uncooperative group did not differ from that in the cooperative group (22.0% vs. 19.7%, P=0.246). The diagnostic performances of the PHSST in the conservative approach were as follows: 79.5% sensitivity (95% confidence interval [CI], 75.5%–83.1%), 90.2% specificity (95% CI, 88.8%–91.6%), and 0.849 area under the receiver operating characteristic curve (AUC; 95% CI, 0.829–0.868). The sensitivity and specificity were 83.3% (95% CI, 80.0%–86.3%) and 75.2% (95% CI, 73.3%–76.9%), respectively, in the real-world approach and 64.6% (95% CI, 60.5%–68.5%) and 91.9% (95% CI, 90.7%–93.0%), respectively, in the contrapositive approach. No significant difference was evident in the AUC between the real-world approach and the contrapositive approach (0.792 [95% CI, 0.775–0.810] vs. 0.782 [95% CI, 0.762–0.803], P>0.05).
Conclusion
We found overestimation (false positive) and underestimation (false negative) in the uncooperative group depending on the scenario-based EMS stroke screening policy for uncooperative prehospital patients suspected of acute stroke.