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

Luke A. Perry, Tom Lucarelli, Jahan C. Penny-Dimri, Matthew D.F. McInnes, Stefania Mondello, Alejandro Bustamante, Joan Montaner, Christian Foerch, Patrick Kwan, Stephen Davis, Bernard Yan

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)390-399
Number of pages10
JournalInternational Journal of Stroke
Volume14
Issue number4
DOIs
Publication statusPublished - Jun 1 2019

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Glial Fibrillary Acidic Protein
Cerebral Hemorrhage
Routine Diagnostic Tests
Meta-Analysis
Early Diagnosis
Stroke
ROC Curve
Point-of-Care Systems
Aptitude
Triage
Blood Proteins
Language
Biomarkers
Databases
Sensitivity and Specificity

ASJC Scopus subject areas

  • Neurology

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Glial fibrillary acidic protein for the early diagnosis of intracerebral hemorrhage : Systematic review and meta-analysis of diagnostic test accuracy. / Perry, Luke A.; Lucarelli, Tom; Penny-Dimri, Jahan C.; McInnes, Matthew D.F.; Mondello, Stefania; Bustamante, Alejandro; Montaner, Joan; Foerch, Christian; Kwan, Patrick; Davis, Stephen; Yan, Bernard.

In: International Journal of Stroke, Vol. 14, No. 4, 01.06.2019, p. 390-399.

Research output: Contribution to journalArticle

Perry, LA, Lucarelli, T, Penny-Dimri, JC, McInnes, MDF, Mondello, S, Bustamante, A, Montaner, J, Foerch, C, Kwan, P, Davis, S & Yan, B 2019, 'Glial fibrillary acidic protein for the early diagnosis of intracerebral hemorrhage: Systematic review and meta-analysis of diagnostic test accuracy', International Journal of Stroke, vol. 14, no. 4, pp. 390-399. https://doi.org/10.1177/1747493018806167
Perry, Luke A. ; Lucarelli, Tom ; Penny-Dimri, Jahan C. ; McInnes, Matthew D.F. ; Mondello, Stefania ; Bustamante, Alejandro ; Montaner, Joan ; Foerch, Christian ; Kwan, Patrick ; Davis, Stephen ; Yan, Bernard. / Glial fibrillary acidic protein for the early diagnosis of intracerebral hemorrhage : Systematic review and meta-analysis of diagnostic test accuracy. In: International Journal of Stroke. 2019 ; Vol. 14, No. 4. pp. 390-399.
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abstract = "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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T2 - Systematic review and meta-analysis of diagnostic test accuracy

AU - Perry, Luke A.

AU - Lucarelli, Tom

AU - Penny-Dimri, Jahan C.

AU - McInnes, Matthew D.F.

AU - Mondello, Stefania

AU - Bustamante, Alejandro

AU - Montaner, Joan

AU - Foerch, Christian

AU - Kwan, Patrick

AU - Davis, Stephen

AU - Yan, Bernard

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AB - 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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