Clinical Utility of Circulating Biomarkers for Diagnosis and Prognosis of Acute Stroke in the Emergency Department: A Narrative Review from Current Evidence to Clinical Implementation.

Acute stroke requires rapid diagnostic classification and prognostic assessment, yet clinical examination and neuroimaging do not fully characterize cerebral injury. This narrative review evaluated the diagnostic, prognostic, and pathophysiological relevance of circulating biomarkers in acute stroke, emphasizing emergency department applications. PubMed, Scopus, Web of Science, Embase, and Google Scholar were searched from January 2015 to August 2026, supplemented by landmark studies. Evidence on brain-specific and systemic biomarkers was synthesized narratively, including multimarker panels, point-of-care testing, and artificial intelligence-based models. Glial fibrillary acidic protein has shown consistent evidence for early differentiation of intracerebral hemorrhage from ischemic stroke. Combinations of glial fibrillary acidic protein and D-dimer showed potential for large-vessel occlusion detection and prehospital triage. Neurofilament light chain, S100B, neuron-specific enolase, matrix metalloproteinase-9, inflammatory indices, hemostatic markers, cardiac biomarkers, and metabolic signatures were associated with severity, neurological deterioration, hemorrhagic transformation, mortality, functional outcome, or recurrence. Clinical translation remains limited by heterogeneity in populations, sampling times, analytical platforms, thresholds, and external validation. Circulating biomarkers are most likely to be useful as adjuncts to established stroke assessment. Multimarker strategies, point-of-care platforms, and integration with clinical scales, neuroimaging, and artificial intelligence may require standardization, multicenter validation, and demonstration of additional clinical value.