Diagnostic markers of stroke and cerebral injury and methods of use thereof
First Claim
13. A method of diagnosing stroke in a subject, comprising:
- analyzing a test sample obtained from a subject exhibiting one or more symptoms associated with the diagnosis of stroke for the presence or amount of a plurality of markers selected from the group consisting of matrix metalloproteinase-9, one or more forms of von Willebrand factor, vascular cell adhesion molecule, and S-100β
, or related markers thereof mimics; and
correlating the presence or amount of said markers in said test sample to the occurrence of a stroke in said subject.
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Accused Products
Abstract
The present invention relates to methods for the diagnosis and evaluation of stroke and transient ischemic attacks. A variety of markers are disclosed for assembling a panel for such diagnosis and evaluation. In various aspects, the invention provides methods for early detection and differentiation of stroke types and transient ischemic attacks, for determining the prognosis of a patient presenting with stroke symptoms, and identifying a patient at risk for cerebral vasospasm. Invention methods provide rapid, sensitive and specific assays to greatly increase the number of patients that can receive beneficial stroke treatment and therapy, and reduce the costs associated with incorrect stroke diagnosis.
277 Citations
67 Claims
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13. A method of diagnosing stroke in a subject, comprising:
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analyzing a test sample obtained from a subject exhibiting one or more symptoms associated with the diagnosis of stroke for the presence or amount of a plurality of markers selected from the group consisting of matrix metalloproteinase-9, one or more forms of von Willebrand factor, vascular cell adhesion molecule, and S-100β
, or related markers thereof mimics; and
correlating the presence or amount of said markers in said test sample to the occurrence of a stroke in said subject.
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14. A method of diagnosing stroke in a subject, comprising:
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analyzing a test sample obtained from a subject exhibiting one or more symptoms associated with the diagnosis of stroke for the presence or amount of a plurality of markers selected from the group consisting of matrix metalloproteinase-9, one or more forms of von Willebrand factor, and vascular cell adhesion molecule, or related markers thereof mimics; and
correlating the presence or amount of said markers in said test sample to the occurrence of a stroke in said subject.
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15. A method of diagnosing stroke in a subject, comprising:
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analyzing a test sample obtained from a subject exhibiting one or more symptoms associated with the diagnosis of stroke for the presence or amount of a plurality of markers selected from the group consisting of one or more forms of von Willebrand factor, vascular cell adhesion molecule, and S-100β
, or related markers thereof mimics; and
correlating the presence or amount of said markers in said test sample to the occurrence of a stroke in said subject.
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16. A method of diagnosing stroke in a subject, comprising:
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analyzing a test sample obtained from a subject exhibiting one or more symptoms associated with the diagnosis of stroke for the presence or amount of a plurality of markers selected from the group consisting of B-type natriuretic peptide, glial fibrillary acidic protein, interleukin-8, β
-nerve growth factor, von Willebrand factor-A1, and C-reactive protein, or related markers thereof mimics; and
correlating the presence or amount of said markers in said test sample to the occurrence of a stroke in said subject.
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18. A method of diagnosing stroke in a subject, comprising:
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analyzing a test sample obtained from a subject exhibiting one or more symptoms associated with the diagnosis of stroke for the presence or amount of a plurality of markers selected from the group consisting of B-type natriuretic peptide, glial fibrillary acidic protein, interleukin-8, creatine kinase-BB, monocyte chemotactic protein-1, and interleukin-1 receptor antagonist, or related markers thereof mimics; and
correlating the presence or amount of said markers in said test sample to the occurrence of a stroke in said subject.
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19. A method of diagnosing stroke in a subject, comprising:
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analyzing a test sample obtained from a subject exhibiting one or more symptoms associated with the diagnosis of stroke for the presence or amount of a plurality of markers selected from the group consisting of B-type natriuretic peptide, glial fibrillary acidic protein, C-reactive protein, creatine kinase-BB, matrix metalloproteinase-9, interleukin-8, and β
-nerve growth factor, or related markers thereof; and
correlating the presence or amount of said markers in said test sample to the occurrence of a stroke in said subject.
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20. A method of diagnosing stroke in a subject, comprising:
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analyzing a test sample obtained from a subject exhibiting one or more symptoms associated with the diagnosis of stroke for the presence or amount of a plurality of markers selected from the group consisting of B-type natriuretic peptide, glial fibrillary acidic protein, C-reactive protein, creatine kinase-BB, caspase-3, monocyte chemotactic protein-1, and von Willebrand factor-integrin, or related markers thereof; and
correlating the presence or amount of said markers in said test sample to the occurrence of a stroke in said subject.
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- 23. A panel comprising a plurality of markers selected to selectively identify the occurrence or nonoccurrence of a stroke in a subject exhibiting one or more symptoms associated with the diagnosis of stroke, wherein said marker(s) are selected to distinguish the occurrence of a stroke in said subject from one or more stroke mimic conditions.
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25. A panel comprising a plurality of markers selected to selectively identify the occurrence or nonoccurrence of an acute stroke in a subject exhibiting one or more symptoms associated with the diagnosis of stroke.
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26. A panel comprising a plurality of markers selected to selectively identify the occurrence or nonoccurrence of a non-acute stroke in a subject exhibiting one or more symptoms associated with the diagnosis of stroke.
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31. A panel according to claim 30, wherein a first set of markers are selected to identify an acute stroke, and a second set of markers are selected to identify a non-acute stroke.
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39-1. A panel according to claim 23, wherein one or more of said markers are selected from the group consisting of matrix metalloproteinase-9, one or more forms of von Willebrand factor, and vascular cell adhesion molecule, or related markers thereof.
- 45. A device comprising a plurality of discretely addressable locations comprising a receptor for one of a plurality of markers selected to selectively identify the occurrence or nonoccurrence of a stroke in a subject exhibiting one or more symptoms associated with the diagnosis of stroke, wherein said marker(s) are selected to distinguish the occurrence of a stroke in said subject from one or more stroke mimic conditions.
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47. A device comprising a plurality of discretely addressable locations comprising a receptor for one of a plurality of markers selected to selectively identify the occurrence or nonoccurrence of an acute stroke in a subject exhibiting one or more symptoms associated with the diagnosis of stroke.
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48. A device comprising a plurality of discretely addressable locations comprising a receptor for one of a plurality of markers selected to selectively identify the occurrence or nonoccurrence of a non-acute stroke in a subject exhibiting one or more symptoms associated with the diagnosis of stroke.
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50-2. A device according to claim 45, wherein said markers are selected from the group consisting of adenylate kinase, brain-derived neurotrophic factor, calbindin-D, ciliary neurtotrophic factor, creatine kinase-BB, glial fibrillary acidic protein, lactate dehydrogenase, myelin basic protein, one or more isoforms of nerve growth factor, neural cell adhesion molecule, neurokinin A, neuron-specific enolase, neurotensin, neuropeptide Y, neurotrophin-3, one or more isoforms of protein kinase C, proteolipid protein, S-100β
- , secretagogin, 14-3-3, thrombomodulin, acute phase reactant, A-type natriuretic peptide, B-type natriuretic peptide, C-type natriuretic peptide, adrenomedullin, endothelin-1, endothelin-2, endothelin-3, β
-thromboglobulin, cardiac troponin I, caspase-3, creatine kinase-MB, D-dimer, fibrinopeptide A, head activator, hemoglobin α
2 chain, interleukin-8, myoglobin, plasmin-α
-2-antiplasmin complex, platelet factor 4, prothrombin fragment 1+2, thrombin-antithrombin III complex, tissue factor, vascular endothelial growth factor, and one or more forms of von Willebrand factor, or related markers thereof.
- , secretagogin, 14-3-3, thrombomodulin, acute phase reactant, A-type natriuretic peptide, B-type natriuretic peptide, C-type natriuretic peptide, adrenomedullin, endothelin-1, endothelin-2, endothelin-3, β
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54. A device according to claim 53, wherein said acute phase reactant is selected from the group consisting of C-reactive protein, E-selectin, insulin-like growth factor-1, intercellular adhesion molecule-1, interleukin-1β
- , interleukin-1 receptor antagonist, interleukin-6, matrix metalloproteinase-3, matrix metalloproteinase-9, monocyte chemotactic protein-1, transforming growth factor β
, tumor necrosis factor α
, and vascular cell adhesion molecule, or related markers thereof.
- , interleukin-1 receptor antagonist, interleukin-6, matrix metalloproteinase-3, matrix metalloproteinase-9, monocyte chemotactic protein-1, transforming growth factor β
Specification