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Oak Ridge Conference |
1 Biosite® Incorporated, 11030 Roselle St., San Diego, CA 92121.
2 Duke University Medical Center, Box 2900, Durham, NC 27710.
aAuthor for correspondence. Fax 858-452-8613; e-mail kbuechler{at}biosite.com.
Abstract
Background: The diagnosis and management of acute ischemic stroke are limited by the lack of rapid diagnostic assays for use in an emergency setting. Computed tomography (CT) scanning is used to diagnose hemorrhagic stroke but is relatively ineffective (<33% sensitive) in detecting ischemic stroke. The ability to correlate blood-borne protein biomarkers with stroke phenotypes would aid in the development of such rapid tests.
Methods: ELISAs for >50 protein biomarkers were developed for use on a high-throughput robotic workstation. These assays were used to screen plasma samples from 214 healthy donors and 223 patients diagnosed with stroke, including 82 patients diagnosed with acute ischemic stroke. Marker assay values were first compared by univariate analysis, and then the top markers were subjected to multivariate analysis to derive a marker panel algorithm for the prediction of stroke.
Results: The top markers from this analysis were S-100b (a marker of astrocytic activation), B-type neurotrophic growth factor, von Willebrand factor, matrix metalloproteinase-9, and monocyte chemotactic protein-1. In a panel algorithm in which three or more marker values above their respective cutoffs were scored as positive, these five markers provided a sensitivity of 92% at 93% specificity for ischemic stroke samples taken within 6 h from symptom onset.
Conclusion: A marker panel approach to the diagnosis of stroke may provide a useful adjunct to CT scanning in the emergency setting.
The following articles in journals at HighWire Press have cited this article:
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  A. K. Saenger and R. H. Christenson Stroke Biomarkers: Progress and Challenges for Diagnosis, Prognosis, Differentiation, and Treatment Clin. Chem., January 1, 2010; 56(1): 21 - 33. [Abstract] [Full Text] [PDF]
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 C. Foerch, J. Montaner, K. L. Furie, M. M. Ning, and E. H. Lo Invited Article: Searching for oracles?: Blood biomarkers in acute stroke Neurology, August 4, 2009; 73(5): 393 - 399. [Abstract] [Full Text] [PDF]
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 D. T. Laskowitz, S. E. Kasner, J. Saver, K. S. Remmel, E. C. Jauch, and BRAIN Study Group Clinical Usefulness of a Biomarker-Based Diagnostic Test for Acute Stroke: The Biomarker Rapid Assessment in Ischemic Injury (BRAIN) Study Stroke, January 1, 2009; 40(1): 77 - 85. [Abstract] [Full Text] [PDF]
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W. Whiteley, M.-C. Tseng, and P. Sandercock Blood Biomarkers in the Diagnosis of Ischemic Stroke: A Systematic Review Stroke, October 1, 2008; 39(10): 2902 - 2909. [Abstract] [Full Text] [PDF]
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 S. Suzuki, C. M. Brown, C. D. Dela Cruz, E. Yang, D. A. Bridwell, and P. M. Wise Timing of estrogen therapy after ovariectomy dictates the efficacy of its neuroprotective and antiinflammatory actions PNAS, April 3, 2007; 104(14): 6013 - 6018. [Abstract] [Full Text] [PDF]
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E. C. Jauch, C. Lindsell, J. Broderick, S. C. Fagan, B. C. Tilley, S. R. Levine, and for the NINDS rt-PA Stroke Study Group Association of Serial Biochemical Markers With Acute Ischemic Stroke: The National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study Stroke, October 1, 2006; 37(10): 2508 - 2513. [Abstract] [Full Text] [PDF]
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O. F. Laterza, V. R. Modur, D. L. Crimmins, J. V. Olander, Y. Landt, J.-M. Lee, and J. H. Ladenson Identification of Novel Brain Biomarkers Clin. Chem., September 1, 2006; 52(9): 1713 - 1721. [Abstract] [Full Text] [PDF]
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M. D. Hill Diagnostic Biomarkers for Stroke: A Stroke Neurologist's Perspective Clin. Chem., November 1, 2005; 51(11): 2001 - 2002. [Full Text] [PDF]
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L. Allard, P. R. Burkhard, P. Lescuyer, J. A. Burgess, N. Walter, D. F. Hochstrasser, and J.-C. Sanchez PARK7 and Nucleoside Diphosphate Kinase A as Plasma Markers for the Early Diagnosis of Stroke Clin. Chem., November 1, 2005; 51(11): 2043 - 2051. [Abstract] [Full Text] [PDF]
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 L. Anderson Candidate-based proteomics in the search for biomarkers of cardiovascular disease J. Physiol., February 15, 2005; 563(1): 23 - 60. [Abstract] [Full Text] [PDF]
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 L. B. Ware, M. D. Eisner, B. T. Thompson, P. E. Parsons, and M. A. Matthay Significance of Von Willebrand Factor in Septic and Nonseptic Patients with Acute Lung Injury Am. J. Respir. Crit. Care Med., October 1, 2004; 170(7): 766 - 772. [Abstract] [Full Text] [PDF]
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J. R. Lynch, R. Blessing, W. D. White, H. P. Grocott, M. F. Newman, and D. T. Laskowitz Novel Diagnostic Test for Acute Stroke Stroke, January 1, 2004; 35(1): 57 - 63. [Abstract] [Full Text] [PDF]
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