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Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 2003 Mar;74(3):322–325. doi: 10.1136/jnnp.74.3.322

S100B as a surrogate marker for successful clot lysis in hyperacute middle cerebral artery occlusion

C Foerch 1, de R Du Mesnil 1, O Singer 1, T Neumann-Haefelin 1, M Buchkremer 1, F Zanella 1, H Steinmetz 1, M Sitzer 1
PMCID: PMC1738319  PMID: 12588916

Abstract

Objectives: The astroglial protein S100B is a marker of cerebral tissue damage. This study investigated whether the serum kinetic of S100B may serve as a surrogate marker of successful clot lysis and early recanalisation (<6 hours) in hyperacute proximal middle cerebral artery (MCA/M1) occlusion.

Methods: The authors prospectively included 23 patients (mean (SD) age, 70.2 (11.0) years) presenting with MCA/M1 occlusion on magnetic resonance angiography (n=18), intra-arterial angiography (IA; n=2), or transcranial Doppler sonography (TCD; n=3) within five hours after symptom onset. Rates of recanalisation and their point of time were determined using TCD or IA. Individual S100B values were determined at hospital admission, every eight hours within the first three days, and at 12 hour intervals from day 4 to day 6. Additionally, the S100B area under the curve (AUC) and the S100B peak value were obtained.

Results: Early recanalisation (<6 hours after symptom onset, n=7) was associated with a significantly lower mean S100B AUC compared with no recanalisation (22.2 (40.1) versus 406.8 (284.4) µg/l per hour; p<0.001). Using receiver operating calculations, a single S100B value obtained 48–96 hours after stroke onset of less than 0.4 µg/l (cut off point) provided a 86% sensitivity and 100% specificty for sufficient MCA/M1 clot lysis <6 hours. The overall accuracy for a single S100B value obtained in the 48–96 hours time window was as high as for the AUC (95.7%).

Conclusion: A single S100B value <0.4 µg/l obtained 48–96 hours after stroke onset indicates succesful clot lysis <6 hours in MCA/M1 occlusion with a high degree of accuracy. Thus, determination of a single S100B value may serve as a surrogate marker of early and sufficient MCA/M1 recanalisation in large scale thrombolytic studies.

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Selected References

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  1. Alexandrov A. V., Demchuk A. M., Felberg R. A., Christou I., Barber P. A., Burgin W. S., Malkoff M., Wojner A. W., Grotta J. C. High rate of complete recanalization and dramatic clinical recovery during tPA infusion when continuously monitored with 2-MHz transcranial doppler monitoring. Stroke. 2000 Mar;31(3):610–614. doi: 10.1161/01.str.31.3.610. [DOI] [PubMed] [Google Scholar]
  2. Alexandrov A. V., Demchuk A. M., Wein T. H., Grotta J. C. Yield of transcranial Doppler in acute cerebral ischemia. Stroke. 1999 Aug;30(8):1604–1609. doi: 10.1161/01.str.30.8.1604. [DOI] [PubMed] [Google Scholar]
  3. Barber P. A., Demchuk A. M., Hudon M. E., Pexman J. H., Hill M. D., Buchan A. M. Hyperdense sylvian fissure MCA "dot" sign: A CT marker of acute ischemia. Stroke. 2001 Jan;32(1):84–88. doi: 10.1161/01.str.32.1.84. [DOI] [PubMed] [Google Scholar]
  4. Burgin W. S., Malkoff M., Felberg R. A., Demchuk A. M., Christou I., Grotta J. C., Alexandrov A. V. Transcranial doppler ultrasound criteria for recanalization after thrombolysis for middle cerebral artery stroke. Stroke. 2000 May;31(5):1128–1132. doi: 10.1161/01.str.31.5.1128. [DOI] [PubMed] [Google Scholar]
  5. Clark W. M., Wissman S., Albers G. W., Jhamandas J. H., Madden K. P., Hamilton S. Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. JAMA. 1999 Dec 1;282(21):2019–2026. doi: 10.1001/jama.282.21.2019. [DOI] [PubMed] [Google Scholar]
  6. Demchuk A. M., Burgin W. S., Christou I., Felberg R. A., Barber P. A., Hill M. D., Alexandrov A. V. Thrombolysis in brain ischemia (TIBI) transcranial Doppler flow grades predict clinical severity, early recovery, and mortality in patients treated with intravenous tissue plasminogen activator. Stroke. 2001 Jan;32(1):89–93. doi: 10.1161/01.str.32.1.89. [DOI] [PubMed] [Google Scholar]
  7. Fieschi C., Argentino C., Lenzi G. L., Sacchetti M. L., Toni D., Bozzao L. Clinical and instrumental evaluation of patients with ischemic stroke within the first six hours. J Neurol Sci. 1989 Jul;91(3):311–321. doi: 10.1016/0022-510x(89)90060-9. [DOI] [PubMed] [Google Scholar]
  8. Fujita N., Hirabuki N., Fujii K., Hashimoto T., Miura T., Sato T., Kozuka T. MR imaging of middle cerebral artery stenosis and occlusion: value of MR angiography. AJNR Am J Neuroradiol. 1994 Feb;15(2):335–341. [PMC free article] [PubMed] [Google Scholar]
  9. Furlan A., Higashida R., Wechsler L., Gent M., Rowley H., Kase C., Pessin M., Ahuja A., Callahan F., Clark W. M. Intra-arterial prourokinase for acute ischemic stroke. The PROACT II study: a randomized controlled trial. Prolyse in Acute Cerebral Thromboembolism. JAMA. 1999 Dec 1;282(21):2003–2011. doi: 10.1001/jama.282.21.2003. [DOI] [PubMed] [Google Scholar]
  10. Grotta J. C., Alexandrov A. V. tPA-associated reperfusion after acute stroke demonstrated by SPECT. Stroke. 1998 Feb;29(2):429–432. doi: 10.1161/01.str.29.2.429. [DOI] [PubMed] [Google Scholar]
  11. Hacke W., Kaste M., Fieschi C., Toni D., Lesaffre E., von Kummer R., Boysen G., Bluhmki E., Höxter G., Mahagne M. H. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS) JAMA. 1995 Oct 4;274(13):1017–1025. [PubMed] [Google Scholar]
  12. Hacke W., Kaste M., Fieschi C., von Kummer R., Davalos A., Meier D., Larrue V., Bluhmki E., Davis S., Donnan G. Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998 Oct 17;352(9136):1245–1251. doi: 10.1016/s0140-6736(98)08020-9. [DOI] [PubMed] [Google Scholar]
  13. Hacke W., Ringleb P., Stingele R. Thrombolysis in acute cerebrovascular disease: indications and limitations. Thromb Haemost. 1999 Aug;82(2):983–986. [PubMed] [Google Scholar]
  14. Hackworthy R. A., Sorensen S. G., Fitzpatrick P. G., Barry W. H., Menlove R. L., Rothbard R. L., Anderson J. L. Dependence of assessment of coronary artery reperfusion during acute myocardial infarction on angiographic criteria and interobserver variability. Am J Cardiol. 1988 Sep 15;62(9):538–542. doi: 10.1016/0002-9149(88)90651-0. [DOI] [PubMed] [Google Scholar]
  15. Heiss W. D., Grond M., Thiel A., von Stockhausen H. M., Rudolf J., Ghaemi M., Löttgen J., Stenzel C., Pawlik G. Tissue at risk of infarction rescued by early reperfusion: a positron emission tomography study in systemic recombinant tissue plasminogen activator thrombolysis of acute stroke. J Cereb Blood Flow Metab. 1998 Dec;18(12):1298–1307. doi: 10.1097/00004647-199812000-00004. [DOI] [PubMed] [Google Scholar]
  16. Herrmann M., Vos P., Wunderlich M. T., de Bruijn C. H., Lamers K. J. 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. 2000 Nov;31(11):2670–2677. doi: 10.1161/01.str.31.11.2670. [DOI] [PubMed] [Google Scholar]
  17. Lewandowski C. A., Frankel M., Tomsick T. A., Broderick J., Frey J., Clark W., Starkman S., Grotta J., Spilker J., Khoury J. Combined intravenous and intra-arterial r-TPA versus intra-arterial therapy of acute ischemic stroke: Emergency Management of Stroke (EMS) Bridging Trial. Stroke. 1999 Dec;30(12):2598–2605. doi: 10.1161/01.str.30.12.2598. [DOI] [PubMed] [Google Scholar]
  18. Missler U., Wiesmann M., Friedrich C., Kaps M. S-100 protein and neuron-specific enolase concentrations in blood as indicators of infarction volume and prognosis in acute ischemic stroke. Stroke. 1997 Oct;28(10):1956–1960. doi: 10.1161/01.str.28.10.1956. [DOI] [PubMed] [Google Scholar]
  19. Molina C. A., Montaner J., Abilleira S., Ibarra B., Romero F., Arenillas J. F., Alvarez-Sabín J. Timing of spontaneous recanalization and risk of hemorrhagic transformation in acute cardioembolic stroke. Stroke. 2001 May;32(5):1079–1084. doi: 10.1161/01.str.32.5.1079. [DOI] [PubMed] [Google Scholar]
  20. Schellinger P. D., Fiebach J. B., Jansen O., Ringleb P. A., Mohr A., Steiner T., Heiland S., Schwab S., Pohlers O., Ryssel H. Stroke magnetic resonance imaging within 6 hours after onset of hyperacute cerebral ischemia. Ann Neurol. 2001 Apr;49(4):460–469. [PubMed] [Google Scholar]
  21. Schellinger P. D., Jansen O., Fiebach J. B., Heiland S., Steiner T., Schwab S., Pohlers O., Ryssel H., Sartor K., Hacke W. Monitoring intravenous recombinant tissue plasminogen activator thrombolysis for acute ischemic stroke with diffusion and perfusion MRI. Stroke. 2000 Jun;31(6):1318–1328. doi: 10.1161/01.str.31.6.1318. [DOI] [PubMed] [Google Scholar]
  22. Stingele R., Bluhmki E., Hacke W. Bootstrap statistics of ECASS II data: just another post hoc analysis of a negative stroke trial? Cerebrovasc Dis. 2001;11(1):30–33. doi: 10.1159/000047608. [DOI] [PubMed] [Google Scholar]
  23. Zanette E. M., Fieschi C., Bozzao L., Roberti C., Toni D., Argentino C., Lenzi G. L. Comparison of cerebral angiography and transcranial Doppler sonography in acute stroke. Stroke. 1989 Jul;20(7):899–903. doi: 10.1161/01.str.20.7.899. [DOI] [PubMed] [Google Scholar]
  24. del Zoppo G. J., Poeck K., Pessin M. S., Wolpert S. M., Furlan A. J., Ferbert A., Alberts M. J., Zivin J. A., Wechsler L., Busse O. Recombinant tissue plasminogen activator in acute thrombotic and embolic stroke. Ann Neurol. 1992 Jul;32(1):78–86. doi: 10.1002/ana.410320113. [DOI] [PubMed] [Google Scholar]

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