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Explorative investigation of biomarkers of brain damage and coagulation system activation in clinical stroke differentiation

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Abstract

Introduction

A simple and accurate method of differentiating ischemic stroke and intracerebral hemorrhage (ICH) is potentially useful to facilitate acute therapeutic management. Blood measurements of biomarkers of brain damage and activation of the coagulation system may potentially serve as novel diagnostic tools for stroke subtypes.

Methods

Ninety-seven stroke patients were prospectively investigated in a multicenter design with blood levels of brain biomarkers S100B, neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP) as well as a coagulation biomarker, activated protein C – protein C inhibitor complex (APC-PCI), within 24 hours of symptom onset.

Results

Eighty-three patients (86 %) had ischemic stroke and fourteen patients (14 %) had ICH. There were no differences in S100B (p = 0.13) and NSE (p = 0.67) levels between patients with ischemic stroke or ICH. However, GFAP levels were significantly higher in ICH patients (p = 0.0057). APC-PCI levels were higher in larger ischemic strokes (p = 0.020). The combination of GFAP and APC-PCI levels, in patients with NIHSS score more than 3, had a sensitivity and negative predictive value of 100 % for ICH in our material (p = 0.0052).

Conclusion

This exploratory study indicated that blood levels of biomarkers GFAP and APC-PCI, prior to neuroimaging, may rule out ICH in a mixed stroke population.

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References

  1. Ingebrigtsen T, Romner B, Marup- Jensen S, et al. (2000) The clinical value of serum S-100 protein measurements in minor head injury: a Scandinavian multicentre study. Brain Inj 14:1047–1055

    Article  PubMed  CAS  Google Scholar 

  2. Raabe A, Seifert V (2000) Protein S- 100B as a serum marker of brain damage in severe head injury: preliminary results. Neurosurg Rev 23:136–138

    Article  PubMed  CAS  Google Scholar 

  3. Romner B, Ingebrigtsen T, Kongstad P, et al. (2000) Traumatic brain damage: serum S-100 protein measurements related to neuroradiological findings. J Neurotrauma 17:641–644

    Article  PubMed  CAS  Google Scholar 

  4. Bottiger BW, Mobes S, Glatzer R, et al. (2001) Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage and outcome after cardiac arrest in humans. Circulation 103:2694–2698

    PubMed  CAS  Google Scholar 

  5. Vos PE, van Gils M, Beems T, Zimmerman C, Verbeek MM (2006) Increased GFAP and S100beta but not NSE serum levels after subarachnoid haemorrhage are associated with clinical severity. Eur J Neurol 13(6):632–638

    Article  PubMed  CAS  Google Scholar 

  6. Undén J, Christensson B, Bellner J, et al. (2004) Serum S100B levels in patients with cerebral and extracerebral infectious disease. Scand J Infect Dis 36:10–13

    Article  PubMed  Google Scholar 

  7. Abraha HD, Butterworth RJ, Bath PM, et al. (1997) Serum S-100 protein, relationship to clinical outcome in acute stroke. Ann Clin Biochem 34:546–550

    PubMed  Google Scholar 

  8. Aurell A, Rosengren LE, Karlsson B, et al. (1991) Determination of S-100 and glial fibrillary acidic protein concentrations in cerebrospinal fluid after brain infarction. Stroke 22:1254–1258

    PubMed  CAS  Google Scholar 

  9. Butterworth RJ, Wassif WS, Sherwood RA, et al. (1996) Serum neuron-specific enolase, carnosinase, and their ratio in acute stroke. An enzymatic test for predicting outcome? Stroke 27:2064–2068

    PubMed  CAS  Google Scholar 

  10. Herrmann M, Vos P, Wunderlich MT, et al. (2000) Release of glial tissuespecific proteins after acute stroke: A comparative analysis of serum concentrations of protein S-100B and glial fibrillary acidic protein. Stroke 31:2670–2677

    PubMed  CAS  Google Scholar 

  11. Persson L, Hardemark HG, Gustafsson J, et al. (1987) S-100 protein and neuron- specific enolase in cerebrospinal fluid and serum: markers of cell damage in human central nervous system. Stroke 18:911–918

    PubMed  CAS  Google Scholar 

  12. Geiger S, Holdenrieder S, Stieber P, Hamann GF, Bruening R, Ma J, Nagel D, Seidel D (2007) Nucleosomes as a new prognostic marker in early cerebral stroke. J Neurol 254(5):617–623

    Article  PubMed  Google Scholar 

  13. Foerch C, Curdt I, Yan B, et al. (2006) Serum glial fibrillary acidic protein as a biomarker for intracerebral haemorrhage in patients with acute stroke. J Neurol Neurosurg Psychiatry 77:181–184

    Article  PubMed  CAS  Google Scholar 

  14. Dahlback B (2005) Blood coagulation and its regulation by anticoagulant pathways: genetic pathogenesis of bleeding and thrombotic diseases. J Intern Med 257:209–223

    Article  PubMed  Google Scholar 

  15. Espana F, Vicente V, Tabernero D, et al. (1990) Determination of plasma protein C inhibitor and of two activated protein C-inhibitor complexes in normals and in patients with intravascular coagulation and thrombotic disease. Thromb Res 59:593–608

    Article  PubMed  CAS  Google Scholar 

  16. Minamikawa K, Wada H, Wakita Y, et al. (1994) Increased activated protein Cprotein C inhibitor complex levels in patients with pulmonary embolism. Journal of thrombosis and haemostasis 71:192–194

    CAS  Google Scholar 

  17. Strandberg K, Astermark J, Bjorgell O, et al. (2001) Complexes between activated protein C and protein C inhibitor measured with a new method: comparison of performance with other markers of hypercoagulability in the diagnosis of deep vein thrombosis. Journal of thrombosis and haemostasis 86:1400–1408

    CAS  Google Scholar 

  18. Strandberg K, Bhiladvala P, Holm J, et al. (2001) A new method to measure plasma levels of activated protein C in complex with protein C inhibitor in patients with acute coronary syndromes. Blood Coagul Fibrinolysis 12:503–510

    Article  PubMed  CAS  Google Scholar 

  19. Tanigawa M, Wada H, Minamikawa K, et al. (1995) Decreased protein C inhibitor after percutaneous transluminal coronary angioplasty in patients with acute myocardial infarction. Am J Hematol 49:1–5

    Article  PubMed  CAS  Google Scholar 

  20. Rosengren LE, Wikkelso C, Hagberg L (1994) A sensitive ELISA for glial fibrillary acidic protein: application in CSF of adults. J Neurosci Methods 51:197–204

    Article  PubMed  CAS  Google Scholar 

  21. Kolbel T, Strandberg K, Mattiasson I, Stenflo J, Lindblad B (2006) Activated protein C-protein C inhibitor complex: a new biological marker for aortic aneurysms. J Vasc Surg 43:935–939

    Article  PubMed  Google Scholar 

  22. Laurell M, Stenflo J, Carlson TH (1990) Turnover of *I-protein C inhibitor and *I-alpha 1-antitrypsin and their complexes with activated protein C. Blood 76:2290–2295

    PubMed  CAS  Google Scholar 

  23. Tei H, Uchiyama S, Koshimizu K, Kobayashi M, Ohara K (1999) Correlation between symptomatic, radiological and etiological diagnosis in acute ischemic stroke. Acta Neurol Scand 99:192–195

    Article  PubMed  CAS  Google Scholar 

  24. Phillips SJ, Dai D, Mitnitski A, et al. on behalf of the GAIN Americas Investigators (2007) Clinical diagnosis of lacunar stroke in the first 6 hours after symptom onset. Analysis of data from the Glycine Antagonist In Neuroprotection (GAIN) Americas Trial. Stroke 38(10):2706–2711

    Article  PubMed  Google Scholar 

  25. Wada R, Aviv RI, Fox AJ, Sahlas DJ, Gladstone DJ, Tomlinson G, Symons SP (2007) CT angiography “spot sign” predicts hematoma expansion in acute intracerebral hemorrhage. Stroke 38(4):1257–1262

    Article  PubMed  Google Scholar 

  26. Bhiladvala P, Strandberg K, Stenflo J, Holm J (2006) Early identification of acute myocardial infarction by activated protein C – protein C inhibitor complex. Thromb Res 118:213–219

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Dept. of Anaesthesiology and Intensive Care, Halmstad Regional Hospital, 30185, Halmstad, Sweden

    Johan Undén MD, PhD

  2. Dept. of Clinical Neuroscience, Lund University, Lund, Sweden

    Eric Campbell, Bo Norrving, Bertil Romner, Arne Lindgren & Gunnar Andsberg

  3. Dept. of Laboratory Medicine, Lund University, Malmö, Sweden

    Karin Strandberg & Johan Stenflo

  4. Dept. of Pharmacology and Clinical Neuroscience, University of Umeå, Umeå, Sweden

    Jan Malm

  5. Dept. of Neuroscience and Physiology, The Sahlgrenska Academy, Göteborg Univeristy, Göteborg, Sweden

    Lars Rosengren

Authors
  1. Johan Undén MD, PhD
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  2. Karin Strandberg
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  3. Jan Malm
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  4. Eric Campbell
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  5. Lars Rosengren
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  6. Johan Stenflo
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  7. Bo Norrving
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  8. Bertil Romner
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  9. Arne Lindgren
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  10. Gunnar Andsberg
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Corresponding author

Correspondence to Johan Undén MD, PhD.

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Undén, J., Strandberg, K., Malm, J. et al. Explorative investigation of biomarkers of brain damage and coagulation system activation in clinical stroke differentiation. J Neurol 256, 72–77 (2009). https://doi.org/10.1007/s00415-009-0054-8

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  • DOI: https://doi.org/10.1007/s00415-009-0054-8

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