Diagnostic Accuracy of Glial Fibrillary Acidic Protein (GFAP) for Differentiating Ischemic Stroke from Intracerebral Hemorrhage: A Systematic Review and Meta-analysis
Faisal Aljamea1, Nicholas Aderinto2, Syed Hasham Ali3, Temitomi Jane Oyedele4, Emmanuel Egbunu5, Gbolahan Olatunji6, Emmanuel Kokori6, Faith Adedayo Adejumo4, Adetola Emmanuel Babalola7
1Vision Colleges, Saudi Arabia, 2Ladoke Akintola University of Technology, Nigeria, 3Dow University of Health Sciences, Pakistan, 4Bowen University, Nigeria, 5Federal Medical Center, Kebbi, Nigeria, 6University of Ilorin, Nigeria, 7Kornberg School of Dentistry, USA
Objective:
To assess the diagnostic accuracy of glial fibrillary acidic protein (GFAP) for distinguishing intracerebral hemorrhage (ICH) from ischemic stroke (IS) in adults using systematic review and meta-analysis.
Background:
Rapidly distinguishing ICH from IS is crucial in stroke management, as treatments differ and neuroimaging is often delayed. GFAP, released into blood after brain injury—especially ICH—has emerged as a potential early biomarker. However, varying study methods and thresholds require systematic evidence on GFAP’s diagnostic value.
Design/Methods:
We systematically reviewed and meta-analyzed studies (PRISMA-DTA) to September 2025, including adults with radiologically confirmed ICH or IS. Two reviewers screened, extracted data, and assessed bias (QUADAS-2). Pooled diagnostic metrics and HSROC curves were calculated. Subgroup analyses compared assay types and sampling times.
Results:
Fourteen studies (1,967 patients: 536 ICH, 1,431 IS) were included. GFAP levels were consistently higher in ICH, especially within four hours of onset. Pooled sensitivity and specificity were 75.5% and 91.5%. Positive and negative likelihood ratios were 8.85 and 0.27, and diagnostic odds ratio was 33.0. HSROC area was 0.93, indicating excellent accuracy. SiMOA assays outperformed ELISA in specificity and DOR. Heterogeneity was low to moderate. Early sampling maximized discriminative accuracy, reflecting rapid astroglial destruction in ICH.
Conclusions:
GFAP is a highly specific, moderately sensitive marker for distinguishing ICH from IS. Its rapid rise after hemorrhage supports use in early stroke triage, especially where neuroimaging is delayed. GFAP testing could improve decision-making and outcomes. Further research should standardize assays, validate cutoffs, and assess point-of-care use in large trials.
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