Age-Related Differences in Diagnostic Accuracy of Plasma Glial Fibrillary Acidic Protein and Tau for Identifying Acute Intracranial Trauma on Computed Tomography: A TRACK-TBI Study

Abstract Traumatic brain injuries (TBIs) and sports-related concussions (SRCs) are the leading causes of hospitalization and death in subjects <45 years old in the USA and Europe. Some biomarkers (BMs) have been used to reduce unnecessary cranial computed tomography (CCT). In recent years, the astroglial S100 calcium-binding B protein (S100B) has prevented approximately 30% of unnecessary CCTs. Glial fibrillary acidic protein (GFAP) has also been studied in direct comparison with S100B. The aim of our cumulative meta-analysis (cMA) is to compare – in the context of hospital emergency departments or SRC conditions – the differences in diagnostic accuracy (DA), sensitivity (Se) and specificity (Sp) of GFAP and S100B. The main cMA inclusion criterion was the assessment of both BMs in the included subjects since 2010, with blood samples drawn 1–30 h from the suspected TBI or SRC. The risk-of-bias (RoB) score was determined, and both the publication bias (with the Begg, Egger and Duval trim-and-fill tests) and sensitivity (with the box-and-whiskers plot) were analyzed for outliers. Seven studies with 899 subjects and nine observations (samples) were included. The diagnostic odds ratios (dORs) with their prediction intervals (PIs), Se and Sp (analyzed with a hierarchical model to respect the binomial data structure) were assessed, and a random-effects MA and a cMA of the difference in the BMs dOR natural logarithms (logOR(G-S)) between the BMs were performed. The cMA of dOR(G-S) was significant (5.78 (CI 2–16.6)) probably preventing approximately 50% of unnecessary CCTs. Further work is needed to standardize and harmonize GFAP laboratory methods.

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Glial fibrillary acidic protein for the early diagnosis of intracerebral hemorrhage: Systematic review and meta-analysis of diagnostic test accuracy

International Journal of Stroke ◽

10.1177/1747493018806167 ◽

2018 ◽

Vol 14 (4) ◽

pp. 390-399 ◽

Cited By ~ 9

Author(s):

Luke A Perry ◽

Tom Lucarelli ◽

Jahan C Penny-Dimri ◽

Matthew DF McInnes ◽

Stefania Mondello ◽

...

Keyword(s):

Glial Fibrillary Acidic Protein ◽

Intracerebral Hemorrhage ◽

Diagnostic Accuracy ◽

Symptom Onset ◽

Hospital Setting ◽

Acidic Protein ◽

Test Accuracy ◽

Primary Analysis ◽

Significant Difference ◽

Study Heterogeneity

Background and aims Glial fibrillary acidic protein (GFAP) has shown promise in several studies for its ability to diagnose intracerebral hemorrhage (ICH). We evaluated the diagnostic accuracy of blood GFAP level to differentiate (ICH) from acute ischemic stroke (AIS) and stroke mimics, both overall, and in the first three hours after symptom onset. Methods We searched multiple databases, without language restriction, from inception until December 2017. Hierarchical summary receiver operating characteristic (HSROC) modeling was used to meta-analyze results. We conducted subgroup analyses restricted to blood samples collected within 0–60, 60–120, and 120–180 min time groups after symptom onset, to evaluate diagnostic accuracy in the early pre-hospital phase. Between and within study heterogeneity was explored using meta-regression. Results The search identified 199 potentially relevant citations from which 11 studies involving 1297 participants (350 ICH, 947 AIS, or mimic) were included. The pooled sensitivity, specificity, and area under the HSROC curve were 0.756 (95% CI 0.630–0.849), 0.945 (95% CI 0.858–0.980), and 0.904 (95% CI 0.878–0.931), respectively. Differences in assays used, but not the other covariates, partially explained between-study heterogeneity ( p = 0.034). The summary estimates for the 0–60, 60–120, and 120–180 min subgroups were comparable to the primary analysis and there was no statistically significant difference in diagnostic accuracy between subgroups. Conclusions GFAP is a promising diagnostic biomarker for ICH diagnosis in the early pre-hospital phase. Test accuracy is affected by assay subtype, but there are still unexplained sources of heterogeneity. High quality, international multi-center trials are warranted to develop and validate a point-of-care GFAP assay for the rapid triage and evaluation of acute stroke in the pre-hospital setting.

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Abstract WP441: Diagnostic Accuracy of Glial Fibrillary Acidic Protein and Ubiquitin Carboxy-Terminal Hydrolase-L1 for Differentiating Acute Intracerebral Hemorrhage From Ischemic Stroke

Stroke ◽

10.1161/str.50.suppl_1.wp441 ◽

2019 ◽

Vol 50 (Suppl_1) ◽

Author(s):

Sebastian Luger ◽

Henriette S Jæger ◽

Joanna Dixon ◽

Jan H Schaefer ◽

Ferdinand O Bohmann ◽

...

Keyword(s):

Ischemic Stroke ◽

Glial Fibrillary Acidic Protein ◽

Intracerebral Hemorrhage ◽

Diagnostic Accuracy ◽

Acidic Protein ◽

Acute Intracerebral Hemorrhage ◽

Carboxy Terminal

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Diagnostic Accuracy of Plasma Glial Fibrillary Acidic Protein for Differentiating Intracerebral Hemorrhage and Cerebral Ischemia in Patients with Symptoms of Acute Stroke

Clinical Chemistry ◽

10.1373/clinchem.2011.172676 ◽

2012 ◽

Vol 58 (1) ◽

pp. 237-245 ◽

Cited By ~ 72

Author(s):

Christian Foerch ◽

Marion Niessner ◽

Tobias Back ◽

Michael Bauerle ◽

Gian Marco De Marchis ◽

...

Keyword(s):

Ischemic Stroke ◽

Glial Fibrillary Acidic Protein ◽

Intracerebral Hemorrhage ◽

Diagnostic Accuracy ◽

Acute Stroke ◽

Symptom Onset ◽

Point Of Care ◽

Area Under The Curve ◽

Acidic Protein ◽

Stroke Mimic

Abstract BACKGROUND Glial fibrillary acidic protein (GFAP) is a biomarker candidate indicative of intracerebral hemorrhage (ICH) in patients with symptoms of acute stroke. GFAP is released rapidly in the presence of expanding intracerebral bleeding, whereas a more gradual release occurs in ischemic stroke. In this study the diagnostic accuracy of plasma GFAP was determined in a prospective multicenter approach. METHODS Within a 1-year recruitment period, patients suspected of having acute (symptom onset <4.5 h before admission) hemispheric stroke were prospectively included into the study in 14 stroke centers in Germany and Switzerland. A blood sample was collected at admission, and plasma GFAP was measured by use of an electrochemiluminometric immunoassay. The final diagnosis, established at hospital discharge, was classified as ICH, ischemic stroke, or stroke mimic. RESULTS The study included 205 patients (39 ICH, 163 ischemic stroke, 3 stroke mimic). GFAP concentrations were increased in patients with ICH compared with patients with ischemic stroke [median (interquartile range) 1.91 μg/L (0.41–17.66) vs 0.08 μg/L (0.02–0.14), P < 0.001]. Diagnostic accuracy of GFAP for differentiating ICH from ischemic stroke and stroke mimic was high [area under the curve 0.915 (95% CI 0.847–0.982), P < 0.001]. A GFAP cutoff of 0.29 μg/L provided diagnostic sensitivity of 84.2% and diagnostic specificity of 96.3% for differentiating ICH from ischemic stroke and stroke mimic. CONCLUSIONS Plasma GFAP analysis performed within 4.5 h of symptom onset can differentiate ICH and ischemic stroke. Studies are needed to evaluate a GFAP point-of-care system that may help optimize the prehospital triage and management of patients with symptoms of acute stroke.

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