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Serum von Willebrand factor, matrix metalloproteinase-9, and vascular endothelial growth factor levels predict the onset of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.

Publication ,  Journal Article
McGirt, MJ; Lynch, JR; Blessing, R; Warner, DS; Friedman, AH; Laskowitz, DT
Published in: Neurosurgery
November 2002

OBJECTIVE: Endothelial damage and intimal proliferation occur in vasospastic cerebral arteries after subarachnoid hemorrhage (SAH). In the peripheral vasculature, endothelial damage increases intimal matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) levels, causing neointimal proliferation. We hypothesized that serum von Willebrand factor (vWF) (a marker of endothelial cell death), MMP-9, and VEGF levels could serve as prognostic markers in predicting the occurrence of cerebral vasospasm. METHODS: Venous serum vWF, MMP-9, and VEGF levels were prospectively measured daily, for 12 days or until the onset of vasospasm, for 45 consecutive patients admitted with SAH (n = 38) or admitted for elective aneurysm clipping (control subjects, n = 7). The development of transcranial Doppler flow velocities of more than 180 cm/s and/or new focal neurological deficits with angiographically confirmed vasospasm was considered the onset of vasospasm. To establish whether these markers were specific for vasospasm versus ischemia, blood samples were obtained from a concurrent group of 42 patients within 24 hours after stroke onset unrelated to SAH. RESULTS: Fifty-seven percent of patients (22 of 38 patients) developed vasospasm, 4 to 11 days after SAH (median, 7 d). Mean peak serum vWF, MMP-9, and VEGF levels were increased in the SAH prevasospasm cohort, compared with the SAH nonvasospasm cohort (vWF, 5526 +/- 929 versus 4934 +/- 599 ng/ml, P = 0.01; MMP-9, 705 +/- 338 versus 438 +/- 154 ng/ml, P = 0.006; VEGF, 0.12 +/- 0.06 versus 0.06 +/- 0.06 ng/ml, P = 0.023). Mean peak vWF, MMP-9, and VEGF levels for the focal ischemia cohort (vWF, 4645 +/- 875 ng/ml, P = 0.01; MMP-9, 250 +/- 308 ng/ml, P = 0.001; VEGF, 0.03 +/- 0.04 ng/ml, P = 0.001) were markedly lower in comparison with the SAH prevasospasm cohort and were unchanged in comparison with the control cohort. vWF levels of more than 5500 ng/ml, VEGF levels of more than 0.12 ng/ml, and MMP levels of more than 700 ng/ml each independently increased the odds of subsequent vasospasm (18-, 20-, and 25-fold, respectively). CONCLUSION: The development of cerebral vasospasm after SAH was preceded by increases in serum vWF, MMP-9, and VEGF levels. Increased serum vWF, MMP-9, and VEGF levels could accurately predict the onset of cerebral vasospasm after SAH. These factors were not elevated by SAH alone or in a separate cohort of patients with ischemic stroke, suggesting that these factors might play a role in the pathogenesis of human cerebral vasospasm.

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Published In

Neurosurgery

DOI

ISSN

0148-396X

Publication Date

November 2002

Volume

51

Issue

5

Start / End Page

1128 / 1134

Location

United States

Related Subject Headings

  • von Willebrand Factor
  • Vasospasm, Intracranial
  • Vascular Endothelial Growth Factors
  • Vascular Endothelial Growth Factor A
  • Subarachnoid Hemorrhage
  • Neurology & Neurosurgery
  • Middle Aged
  • Matrix Metalloproteinase 9
  • Male
  • Lymphokines
 

Citation

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McGirt, M. J., Lynch, J. R., Blessing, R., Warner, D. S., Friedman, A. H., & Laskowitz, D. T. (2002). Serum von Willebrand factor, matrix metalloproteinase-9, and vascular endothelial growth factor levels predict the onset of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurgery, 51(5), 1128–1134. https://doi.org/10.1097/00006123-200211000-00005
McGirt, Matthew J., John R. Lynch, Robert Blessing, David S. Warner, Allan H. Friedman, and Daniel T. Laskowitz. “Serum von Willebrand factor, matrix metalloproteinase-9, and vascular endothelial growth factor levels predict the onset of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.Neurosurgery 51, no. 5 (November 2002): 1128–34. https://doi.org/10.1097/00006123-200211000-00005.
McGirt, Matthew J., et al. “Serum von Willebrand factor, matrix metalloproteinase-9, and vascular endothelial growth factor levels predict the onset of cerebral vasospasm after aneurysmal subarachnoid hemorrhage.Neurosurgery, vol. 51, no. 5, Nov. 2002, pp. 1128–34. Pubmed, doi:10.1097/00006123-200211000-00005.
Journal cover image

Published In

Neurosurgery

DOI

ISSN

0148-396X

Publication Date

November 2002

Volume

51

Issue

5

Start / End Page

1128 / 1134

Location

United States

Related Subject Headings

  • von Willebrand Factor
  • Vasospasm, Intracranial
  • Vascular Endothelial Growth Factors
  • Vascular Endothelial Growth Factor A
  • Subarachnoid Hemorrhage
  • Neurology & Neurosurgery
  • Middle Aged
  • Matrix Metalloproteinase 9
  • Male
  • Lymphokines