Skip to main content
SpringerLink
Log in

A Literature Review of the Feasibility of Glial Fibrillary Acidic Protein as a Biomarker for Stroke and Traumatic Brain Injury

  • Review Article
  • Published:
Molecular Diagnosis & Therapy Aims and scope Submit manuscript

Abstract

Traumatic brain injuries (TBIs) are potentially lethal medical conditions, with symptoms that can overlap with symptoms of injuries outside the brain. In many cases, current diagnostic methods do not fully distinguish acute brain injury from other organ damage. In the management of stroke patients, the choice of treatment depends on whether the stroke is ischemic or hemorrhagic; however, no quick lab diagnostic tests are available to distinguish between the two types of strokes. As a result, patient triage, disposition, and patient management decisions may be delayed for patients with suspected TBI and stroke.

Glial fibrillary acidic protein (GFAP), a brain-specific biomarker that is released into the blood following TBI and stroke, is being explored for potential diagnostic and prognostic value in these indications. We therefore conducted a review of MEDLINE-indexed publications from 2004 to 2011 to evaluate the current status of GFAP as a prognostic and diagnostic tool for TBI and stroke within the context of current published guidelines.

Our review suggests that GFAP could provide clinically valuable information for the prognosis of TBI and stroke, but it is still at an early stage of development as a biomarker. Several TBI studies have shown elevated GFAP levels following a TBI event to be associated with greater severity of injury, poorer outcomes, and increased mortality. Clinical studies also indicate that GFAP has potential clinical utility in the differential diagnosis of various types of stroke.

However, more clinical research will be required to determine the ability of GFAP levels to diagnose TBI in heterogeneous patient populations, as well as the ability of GFAP to differentiate between ischemic stroke (IS), intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), and non-stroke conditions in populations of patients with suspected rather than confirmed stroke. Additional clinical studies will also be required to define the temporal patterns of GFAP release in IS, ICH, SAH, and TBI, and their potential use in the differential diagnosis of these conditions. Finally, such research could demonstrate the ability of GFAP test results to provide unique clinical information that informs management decisions for TBI and stroke patients.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Table IV
Table V
Table VI
Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Chestnut RM, Ghajar J, Maas AIR, et al. Early indicators of prognosis in severe traumatic brain injury. New York: Brain Trauma Foundation, 2009 Oct [online]. Available from: http://www.braintrauma.org/pdf/protected/prognosis_guidelines.pdf [Accessed 2012 Mar 14]

    Google Scholar 

  2. Jager TE, Weiss HB, Coben JH, et al. Traumatic brain injuries evaluated in U.S. emergency departments, 1992–1994. Acad Emerg Med 2000 Feb; 7(2): 134–40

    Article  PubMed  CAS  Google Scholar 

  3. Rutland-Brown W, Langlois JA, Thomas KE, et al. Incidence of traumatic brain injury in the United States, 2003. J Head Trauma Rehabil 2006 Nov–Dec; 21(6): 544–8

    Article  PubMed  Google Scholar 

  4. Berger RP. The use of serum biomarkers to predict outcome after traumatic brain injury in adults and children. J Head Trauma Rehabil 2006 Jul–Aug; 21(4): 315–33

    Article  PubMed  Google Scholar 

  5. Jagoda AS, Bazarian JJ, Bruns Jr JJ, et al. Clinical policy: neuroimaging and decisionmaking in adult mild traumatic brain injury in the acute setting. Ann Emerg Med 2008 Dec; 52(6): 714–48

    Article  PubMed  Google Scholar 

  6. Hergenroeder GW, Redell JB, Moore AN, et al. Biomarkers in the clinical diagnosis and management of traumatic brain injury. Mol Diagn Ther 2008; 12(6): 345–58

    Article  PubMed  CAS  Google Scholar 

  7. Nylén K, Csajbok LZ, Ost M, et al. Serum glial fibrillary acidic protein is related to focal brain injury and outcome after aneurysmal subarachnoid hemorrhage. Stroke 2007 May; 38(5): 1489–94

    Article  PubMed  Google Scholar 

  8. Jennett B. Epidemiology of head injury. J Neurol Neurosurg Psychiatry 1996 Apr; 60(4): 362–9

    Article  PubMed  CAS  Google Scholar 

  9. National Center for Health Statistics, Centers for Disease Control and Prevention. National hospital ambulatory medical care survey: emergency department file (2002). CD-ROM series 13, no. 33. Atlanta (GA): National Center for Health Statistics, Centers for Disease Control and Prevention, 2000

  10. Steyerberg EW, Mushkudiani N, Perel P, et al. Predicting outcome after traumatic brain injury: development and international validation of prognostic scores based on admission characteristics. PLoS Med 2008 Aug 5; 5(8): e165; discussion e165

    Article  PubMed  Google Scholar 

  11. Langlois J, Rutland-Brown W, Thomas KE. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Atlanta (GA): Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, 2004

    Google Scholar 

  12. American Heart Association. About stroke [online]. Available from URL: http://www.strokeassociation.org/STROKEORG/AboutStroke/About-Stroke_UCM_308529_SubHomePage.jsp [Accessed 2011 Nov 11, 2011]

  13. Centers for Disease Control and Prevention. Vital statistics data available online. Mortality multiple cause files: 2008 [online]. Available from URL: http://www.cdc.gov/nchs/data_access/Vitalstatsonline.htm#Mortality_Multiple [Accessed 2011 Sep 23]

  14. Hill MD. Diagnostic biomarkers for stroke: a stroke neurologist’s perspective. Clin Chem 2005 Nov; 51(11): 2001–2

    Article  PubMed  CAS  Google Scholar 

  15. Foerch C, Curdt I, Yan B, et al. Serum glial fibrillary acidic protein as a biomarker for intracerebral haemorrhage in patients with acute stroke. J Neurol Neurosurg Psychiatry 2006 Feb; 77(2): 181–4

    Article  PubMed  CAS  Google Scholar 

  16. Korfias S, Papadimitriou A, Stranjalis G, et al. Serum biochemical markers of brain injury. Mini Rev Med Chem 2009 Feb; 9(2): 227–34

    Article  PubMed  CAS  Google Scholar 

  17. Vissers JL, Mersch ME, Rosmalen CF, et al. Rapid immunoassay for the determination of glial fibrillary acidic protein (GFAP) in serum. Clin Chim Acta 2006 Apr; 366(1–2): 336–40

    Article  PubMed  CAS  Google Scholar 

  18. Missler U, Wiesmann M, Wittmann G, et al. Measurement of glial fibrillary acidic protein in human blood: analytical method and preliminary clinical results. Clin Chem 1999 Jan; 45(1): 138–41

    PubMed  CAS  Google Scholar 

  19. Petzold A, Keir G, Green AJ, et al. An ELISA for glial fibrillary acidic protein. J Immunol Methods 2004 Apr; 287(1–2): 169–77

    Article  PubMed  CAS  Google Scholar 

  20. Wunderlich MT, Wallesch CW, Goertler M. Release of glial fibrillary acidic protein is related to the neurovascular status in acute ischemic stroke. Eur J Neurol 2006 Oct; 13(10): 1118–23

    Article  PubMed  CAS  Google Scholar 

  21. Centre for Evidence Based Medicine [CEBM]. Oxford Centre for Evidence-Based Medicine —levels of evidence. Oxford: CEBM, 2009 Mar [online]. Available from URL: http://www.cebm.net/index.aspx?o=1025 [Accessed 2012 Feb 21]

  22. Honda M, Tsuruta R, Kaneko T, et al. Serum glial fibrillary acidic protein is a highly specific biomarker for traumatic brain injury in humans compared with S-100B and neuron-specific enolase. J Trauma 2010 Jul; 69(1): 104–9

    Article  PubMed  CAS  Google Scholar 

  23. Lumpkins KM, Bochicchio GV, Keledjian K, et al. Glial fibrillary acidic protein is highly correlated with brain injury. J Trauma 2008 Oct; 65(4): 778–82; discussion 782-4

    Article  PubMed  CAS  Google Scholar 

  24. Nylén K, Ost M, Csajbok LZ, et al. Increased serum-GFAP in patients with severe traumatic brain injury is related to outcome. J Neurol Sci 2006 Jan 15; 240(1–2): 85–91

    Article  PubMed  Google Scholar 

  25. Pelinka LE, Kroepfl A, Schmidhammer R, et al. Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma. J Trauma 2004 Nov; 57(5): 1006–12

    Article  PubMed  CAS  Google Scholar 

  26. Wiesmann M, Steinmeier E, Magerkurth O, et al. Outcome prediction in traumatic brain injury: comparison of neurological status, CT findings, and blood levels of S100B and GFAP. Acta Neurol Scand 2010 Mar; 121(3): 178–85

    Article  PubMed  CAS  Google Scholar 

  27. Dvorak F, Haberer I, Sitzer M, et al. Characterisation of the diagnostic window of serum glial fibrillary acidic protein for the differentiation of intracerebral haemorrhage and ischaemic stroke. Cerebrovasc Dis 2009; 27(1): 37–41

    Article  PubMed  CAS  Google Scholar 

  28. Unden J, Strandberg K, Malm J, et al. Explorative investigation of biomarkers of brain damage and coagulation system activation in clinical stroke differentiation. J Neurol 2009 Jan; 256(1): 72–7

    Article  PubMed  CAS  Google Scholar 

  29. Vos PE, vanGils M, Beems T, et al. Increased GFAP and S100beta but not NSE serum levels after subarachnoid haemorrhage are associated with clinical severity. Eur J Neurol 2006 Jun; 13(6): 632–8

    Article  PubMed  CAS  Google Scholar 

  30. Pelinka LE, Kroepfl A, Leixnering M, et al. GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome. J Neurotrauma 2004 Nov; 21(11): 1553–61

    Article  PubMed  Google Scholar 

  31. Vos PE, Jacobs B, Andriessen TM, et al. GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort study. Neurology 2010 Nov 16; 75(20): 1786–93

    Article  PubMed  CAS  Google Scholar 

  32. Vos PE, Lamers KJ, Hendriks JC, et al. Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury. Neurology 2004 Apr 27; 62(8): 1303–10

    Article  PubMed  CAS  Google Scholar 

  33. Foerch C, Niessner M, Back T, et al. Diagnostic accuracy of plasma glial fibrillary acidic protein for differentiating intracerebral hemorrhage and cerebral ischemia in patients with symptoms of acute stroke. Clin Chem 2012 Jan; 58(1): 237–45

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The research presented in this manuscript was funded by Roche Diagnostics Ltd. The authors take full responsibility for the contents and opinions expressed herein.

Leora Schiff and Nandini Hadker are employees of United BioSource Corporation. Silvia Weiser and Carsten Rausch are employees of Roche Diagnostics GmbH and Roche Diagnostics Ltd, respectively, and Carsten Rausch holds non-voting shares in Roche Diagnostics Ltd. The authors have no other conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

  1. United BioSource Corporation, Lexington, MA, USA

    Leora Schiff (Project Manager) & Nandini Hadker

  2. Roche Diagnostics GmbH, Penzberg, Germany

    Silvia Weiser

  3. Roche Diagnostics Ltd., Rotkreuz, Switzerland

    Carsten Rausch

Authors
  1. Leora Schiff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nandini Hadker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Silvia Weiser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carsten Rausch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leora Schiff.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schiff, L., Hadker, N., Weiser, S. et al. A Literature Review of the Feasibility of Glial Fibrillary Acidic Protein as a Biomarker for Stroke and Traumatic Brain Injury. Mol Diagn Ther 16, 79–92 (2012). https://doi.org/10.1007/BF03256432

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03256432

Keywords

Search

Navigation