Skip to main content
Log in

Serum glial fibrillary acidic protein as a biomarker for differentiating intracerebral hemorrhage and ischemic stroke in patients with symptoms of acute stroke: a systematic review and meta-analysis

  • Review Article
  • Published:
Neurological Sciences Aims and scope Submit manuscript

Abstract

Serum glial fibrillary acidic protein (GFAP) has been reported to have high diagnosis accuracy for differentiating intracerebral hemorrhage (ICH) from ischemic stroke (IS) in patients within acute phase of stroke symptom onset. Our purpose was to perform a systematic review and diagnostic meta-analysis to evaluate the valuation of serum GFAP in the early identification of ICH and IS. We searched MEDLINE, EMBASE and other electronic databases for diagnostic accuracy studies that compared serum GFAP with standard clinical diagnosis of ICH and IS in patients with symptoms of acute stroke. All publication years were included through to April 2013. The sensitivity (SEN), specificity (SPE), and positive and negative likelihood ratios (PLR and NLR, respectively) of serum GFAP for differentiating ICH and IS were pooled using a bivariate meta-analysis. Summary receiver operating characteristic curves were used to summarize overall test performance. A total of five trials met our inclusion criteria. The summarized estimates of serum GFAP for the differentiation of ICH and IS within 24 h of symptom onset were as follows: SEN, 81.1 % (95 % CI, 72.6–87.5 %); SPE, 95.2 % (95 % CI 82.1–98.9 %); PLR, 16.945 (95 % CI 4.173–68.803); NLR, 0.198 (95 % CI 0.133–0.296), significant heterogeneity was present. The four summary estimates of serum GFAP for patients within 1–6 h of symptom onset were 81.1 % (95 % CI 72.5–88.0 %), 97.0 % (95 % CI 94.3–98.4 %), 26.786 (95 % CI 13.979–51.324), 0.191 (95 % CI 0.126–0.291), respectively, with no obvious heterogeneity. Serum GFAP is a sensitive and specific test for differentiating ICH and IS in patients within 1–6 h of acute stroke symptom onset.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Cheung RT (2007) Update on medical and surgical management of intracerebral hemorrhage. Rev Recent Clin Trials 2(3):174–181

    Article  PubMed  Google Scholar 

  2. Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, Grubb RL, Higashida RT, Jauch EC, Kidwell C, Lyden PD, Morgenstern LB, Qureshi AI, Rosenwasser RH, Scott PA, Wijdicks EF, American Heart A, American Stroke Association Stroke C, Clinical Cardiology C, Cardiovascular R, Intervention C, Atherosclerotic Peripheral Vascular D, Quality of Care Outcomes in Research Interdisciplinary Working G (2007) Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke: J Cereb Circ 38(5):1655–1711. doi:10.1161/STROKEAHA.107.181486

    Article  Google Scholar 

  3. Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: gFAP-thirty-one years (1969–2000). Neurochem Res 25(9–10):1439–1451

    Article  PubMed  CAS  Google Scholar 

  4. Missler U, Wiesmann M, Wittmann G, Magerkurth O, Hagenstrom H (1999) Measurement of glial fibrillary acidic protein in human blood: analytical method and preliminary clinical results. Clin Chem 45(1):138–141

    PubMed  CAS  Google Scholar 

  5. Foerch C, Curdt I, Yan B, Dvorak F, Hermans M, Berkefeld J, Raabe A, Neumann-Haefelin T, Steinmetz H, Sitzer M (2006) Serum glial fibrillary acidic protein as a biomarker for intracerebral haemorrhage in patients with acute stroke. J Neurol Neurosurg Psychiatry 77(2):181–184. doi:10.1136/jnnp.2005.074823

    Article  PubMed  CAS  Google Scholar 

  6. Unden J, Strandberg K, Malm J, Campbell E, Rosengren L, Stenflo J, Norrving B, Romner B, Lindgren A, Andsberg G (2009) Explorative investigation of biomarkers of brain damage and coagulation system activation in clinical stroke differentiation. J Neurol 256(1):72–77. doi:10.1007/s00415-009-0054-8

    Article  PubMed  CAS  Google Scholar 

  7. Dvorak F, Haberer I, Sitzer M, Foerch C (2009) Characterisation of the diagnostic window of serum glial fibrillary acidic protein for the differentiation of intracerebral haemorrhage and ischaemic stroke. Cerebrovasc Dis 27(1):37–41. doi:10.1159/000172632

    Article  PubMed  CAS  Google Scholar 

  8. Foerch C, Niessner M, Back T, Bauerle M, De Marchis GM, Ferbert A, Grehl H, Hamann GF, Jacobs A, Kastrup A, Klimpe S, Palm F, Thomalla G, Worthmann H, Sitzer M, Group BFS (2012) Diagnostic accuracy of plasma glial fibrillary acidic protein for differentiating intracerebral hemorrhage and cerebral ischemia in patients with symptoms of acute stroke. Clin Chem 58(1):237–245. doi:10.1373/clinchem.2011.172676

    Article  PubMed  CAS  Google Scholar 

  9. Whiting P, Rutjes AW, Reitsma JB, Bossuyt PM, Kleijnen J (2003) The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol 3:25. doi:10.1186/1471-2288-3-25

    Article  PubMed  Google Scholar 

  10. Wunderlich MT, Wallesch CW, Goertler M (2006) Release of glial fibrillary acidic protein is related to the neurovascular status in acute ischemic stroke. Eur J Neurol 13(10):1118–1123. doi:10.1111/j.1468-1331.2006.01435.x (The official journal of the European Federation of Neurological Societies)

    Article  PubMed  CAS  Google Scholar 

  11. Jaeschke R, Guyatt GH, Sackett DL (1994) Users’ guides to the medical literature. III. How to use an article about a diagnostic test. B. What are the results and will they help me in caring for my patients? The Evidence-Based Medicine Working Group. JAMA 271(9):703–707

    Article  PubMed  CAS  Google Scholar 

  12. Hergenroeder GW, Redell JB, Moore AN, Dash PK (2008) Biomarkers in the clinical diagnosis and management of traumatic brain injury. Mol Diagn Ther 12(6):345–358. doi:10.2165/1250444-200812060-00002

    Article  PubMed  CAS  Google Scholar 

  13. Vissers JL, Mersch ME, Rosmalen CF, van Heumen MJ, van Geel WJ, Lamers KJ, Rosmalen FM, Swinkels LM, Thomsen J, Herrmann M (2006) Rapid immunoassay for the determination of glial fibrillary acidic protein (GFAP) in serum. Clin Chim Acta: Int J Clin Chem 366(1–2):336–340. doi:10.1016/j.cca.2005.11.017

    Article  CAS  Google Scholar 

  14. Berger RP (2006) The use of serum biomarkers to predict outcome after traumatic brain injury in adults and children. J Head Trauma Rehabil 21(4):315–333

    Article  PubMed  Google Scholar 

  15. McComb RD, Burger PC (1985) Pathologic analysis of primary brain tumors. Neurol Clin 3(4):711–728

    PubMed  CAS  Google Scholar 

  16. El-Jawahri A, Patel D, Zhang M, Mladkova N, Chakravarti A (2008) Biomarkers of clinical responsiveness in brain tumor patients: progress and potential. Mol Diagn Ther 12(4):199–208

    Article  PubMed  CAS  Google Scholar 

  17. Nylen K, Csajbok LZ, Ost M, Rashid A, Blennow K, Nellgard B, Rosengren L (2007) Serum glial fibrillary acidic protein is related to focal brain injury and outcome after aneurysmal subarachnoid hemorrhage. Stroke: J Cereb Circ 38(5):1489–1494. doi:10.1161/STROKEAHA.106.478362

    Article  CAS  Google Scholar 

  18. Herrmann M, Vos P, Wunderlich MT, de Bruijn CH, Lamers KJ (2000) Release of glial tissue-specific proteins after acute stroke: a comparative analysis of serum concentrations of protein S-100B and glial fibrillary acidic protein. Stroke: J Cerebral Circ 31(11):2670–2677

    Article  CAS  Google Scholar 

  19. Mondello S, Jeromin A, Streeter J, Gabrielli A, Schmid K, Tortella F, Hayes RL, Wang KK (2011) Glial fibrillary acidic protein, a sensitive and specific marker in serum for the identification of intracerebral hemorrhage in acute stroke patients: results of improved assay performance. Circulation 124:21(Suppl 1)

    Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sheng-Liang Shi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, J., Zhang, CH., Lin, XL. et al. Serum glial fibrillary acidic protein as a biomarker for differentiating intracerebral hemorrhage and ischemic stroke in patients with symptoms of acute stroke: a systematic review and meta-analysis. Neurol Sci 34, 1887–1892 (2013). https://doi.org/10.1007/s10072-013-1541-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10072-013-1541-3

Keywords

Navigation