GFAP as a Biomarker of Stroke Subtype and Brain Tissue Damage in Acute Stroke: A Systematic Review and Meta-Analysis

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ABSTRACT Background Glial fibrillary acidic protein (GFAP) is a promising blood biomarker that can distinguish intracerebral hemorrhage (ICH) from acute ischemic stroke (AIS). We aimed to summarize the existing evidence regarding: 1) the diagnostic accuracy of GFAP to differentiate ICH from AIS, and from undifferentiated suspected stroke, and 2) characterize GFAP’s diagnostic accuracy across time strata from stroke onset. As a secondary objective, associations between GFAP and clinical and radiological outcomes were narratively summarized. Methods Five databases [(MEDLINE/EMBASE/EBM Reviews/CINAHL Complete/Google Scholar] were searched (03/2026) for studies reporting blood GFAP levels in acute stroke. GFAP levels were analyzed according to time from onset to sampling. Risk of bias was assessed using QUADAS-2 for studies reporting diagnostic accuracy data. Forest plots, pooled sensitivities and specificities were calculated. Results Two reviewers independently screened 6,336 studies; 64 were included for systematic review and 18 for meta-analysis. Risk of bias was low overall among diagnostic studies. For differentiating ICH from AIS, pooled AUC was 0.86 (95% CI: 0.76-0.92), pooled sensitivity 74.4% (95% CI:63.2-84.2%) and pooled specificity 87.2% (95% CI:77.0-94.7%). For ICH versus undifferentiated suspected stroke, pooled AUC was 0.88 (95% CI: 0.79-0.95), pooled sensitivity 75.4% (95% CI: 63.6–83.3%) and pooled specificity 90.5% (95% CI:88.0-96.2%). Diagnostic precision improved in earlier time strata: <6h: AUC 0.91, sensitivity 75.0%, specificity 92.7%; <2h: AUC 0.96, sensitivity 76.7%, specificity 96.4%. GFAP correlated with ICH volume in 11/12 studies, although smaller hematomas (<10 mL) were frequently associated with GFAP values below limits of detection. Few studies (n=3) suggest higher GFAP levels correlate with greater ischemic injury in AIS. Conclusions As a blood biomarker in acute stroke, GFAP has strong rule-in value (i.e. high specificity) for ICH, which is preserved in earlier time windows. Nevertheless, sensitivity remains limited, restricting its use as a rule-out test, particularly for smaller ICH volumes. Knowledge gaps remain regarding GFAP’s potential in assessing ischemic injury extent in AIS.

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