Blood-Based Protein Biomarkers During the Acute Ischemic Stroke Treatment Window: A Systematic Review
Jan Rahmig1, Aditya Chanpura2, Aaliyah Schultz3, Frank Barone2, Deborah Gustafson3, Alison Baird4
1Neurology, University Hospital Carl Gustav Carus Dresden, 2Neurology, State University of New York Downstate Health Sciences University, 3State University of New York Downstate Health Sciences University, 4SUNY Downstate Medical Center
Objective:
This systematic review aims to summarize the literature on blood-based protein biomarkers measured within 24 hours of acute ischemic stroke (AIS) symptom onset, categorized into the following pathophysiological classes: neurovascular inflammation (MMP-9, TNF-alpha), endothelial function (VCAM-1, ICAM-1), cell migration (E-selectin, P-selectin, L-selectin), markers of glial, astrocytic neuronal origin (NSE, GFAP, S100, S100B) and cardiac dysfunction (BNP, NT-proBNP).
Background:
Rapid and accurate AIS diagnosis is needed to expedite emergent thrombolytic and mechanical thrombectomy treatment. Changes in blood-based protein biomarkers during the first 24 h of AIS, the time window for treatment, could complement imaging techniques and facilitate rapid diagnosis and treatment.
Design/Methods:
We performed a systematic review according to PRISMA guidelines. MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched for eligible studies comparing levels of blood-based protein biomarkers in AIS patients with levels in healthy controls and stroke mimics. Protein biomarkers from the following pathophysiological categories were included: neurovascular inflammation (MMP-9, TNF-alpha), endothelial integrity (VCAM-1, ICAM-1), cell migration (E-Selectin, P-Selectin, L-Selectin), markers of glial and neuronal origin (GFAP, S100, S100B, NSE), and cardiac dysfunction (BNP, NT-proBNP). The literature search was limited to English-language publications before November 7th, 2023.
Results:
A total of 61 studies from 20 different countries were identified, which included in total, 4,644 AIS patients, 2,242 stroke mimics, and 2,777 controls. Studies investigating TNF-alpha, MMP-9, VCAM-1, ICAM-1, E-Selectin, L-Selectin, GFAP, NSE, and S100B showed pronounced methodological heterogeneity, making between-study comparisons difficult. However, in 80% of NT-proBNP and BNP studies, and all P-selectin studies, higher biomarker levels were observed in AIS patients compared to healthy controls and/or patients with stroke mimics.
Conclusions:
None of the biomarkers included showed sufficient evidence for additional diagnostic benefit for AIS. Comprehensive standardized global multicenter studies are needed to (1) permit comparability, (2) enable valid statements about protein-based biomarkers, and (3) reflect real-world scenarios.
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