Invited Article: Searching for oracles?

Emerging data suggest that a wide array of measurable biomarkers in blood may provide a novel window into the pathophysiology of stroke. In this review, we survey the state of progress in the field. Three specific questions are assessed. Can biomarkers augment the clinical examination and powerful brain imaging tools to enhance the accuracy of the diagnostic process? Can biomarkers be used to help triage patients for thrombolytic therapy? Can biomarkers help predict patients who are most susceptible to malignant infarction? Many encouraging molecular candidates have been found that appear to match the known cascades of neurovascular injury after stroke. However, whether these putative biomarkers may indeed have direct clinical utility remains to be quantitatively validated. Larger clinical trials are warranted to establish the sensitivity and specificity of biomarkers for routine use in clinical stroke.

[1]  E. Lo,et al.  Reperfusion injury after stroke: neurovascular proteases and the blood-brain barrier. , 2009, Handbook of clinical neurology.

[2]  E. Vicaut,et al.  Early decompressive surgery in malignant infarction of the middle cerebral artery: a pooled analysis of three randomised controlled trials , 2007, The Lancet Neurology.

[3]  J. Wardlaw,et al.  Distinguishing Between Stroke and Mimic at the Bedside: The Brain Attack Study , 2006, Stroke.

[4]  H. Steinmetz,et al.  Elevated Serum S100B Levels Indicate a Higher Risk of Hemorrhagic Transformation After Thrombolytic Therapy in Acute Stroke , 2007 .

[5]  J. Gregg,et al.  Gene Expression in Peripheral Blood Differs after Cardioembolic Compared with Large-Vessel Atherosclerotic Stroke: Biomarkers for the Etiology of Ischemic Stroke , 2008, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  Joseph F. Clark,et al.  Gene Expression in Blood Changes Rapidly in Neutrophils and Monocytes after Ischemic Stroke in Humans: A Microarray Study , 2006, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[7]  E. Lo,et al.  Involvement of Matrix Metalloproteinase in Thrombolysis-Associated Hemorrhagic Transformation After Embolic Focal Ischemia in Rats , 2002, Stroke.

[8]  W. Hacke,et al.  'Malignant' middle cerebral artery territory infarction : Clinical course and prognostic signs , 1996 .

[9]  A. Baird.  Blood Genomics in Human Stroke , 2007, Stroke.

[10]  J. Arenillas,et al.  Serum Cellular Fibronectin and Matrix Metalloproteinase-9 as Screening Biomarkers for the Prediction of Parenchymal Hematoma After Thrombolytic Therapy in Acute Ischemic Stroke: A Multicenter Confirmatory Study , 2007, Stroke.

[11]  D. Laskowitz,et al.  Panel of Biomarkers Predicts Stroke , 2005, Annals of the New York Academy of Sciences.

[12]  M. Sitzer,et al.  Characterisation of the Diagnostic Window of Serum Glial Fibrillary Acidic Protein for the Differentiation of Intracerebral Haemorrhage and Ischaemic Stroke , 2008, Cerebrovascular Diseases.

[13]  W. White,et al.  Novel Diagnostic Test for Acute Stroke , 2003, Stroke.

[14]  Peter Sandercock,et al.  Blood Biomarkers in the Diagnosis of Ischemic Stroke: A Systematic Review , 2008, Stroke.

[15]  M. A. Moro,et al.  The Prediction of Malignant Cerebral Infarction by Molecular Brain Barrier Disruption Markers , 2005, Stroke.

[16]  M. Corson,et al.  Review of the evidence for the clinical utility of lipoprotein-associated phospholipase A2 as a cardiovascular risk marker. , 2008, The American journal of cardiology.

[17]  T. Neumann-Haefelin,et al.  Serum S100B Predicts a Malignant Course of Infarction in Patients With Acute Middle Cerebral Artery Occlusion , 2004, Stroke.

[18]  Koroshetz Wj,et al.  Tissue plasminogen activator for acute ischemic stroke. , 1996, The New England journal of medicine.

[19]  K. Furie,et al.  Association between tPA therapy and raised early matrix metalloproteinase-9 in acute stroke , 2006, Neurology.

[20]  K. Lewandrowski,et al.  Measurement of a plasma stroke biomarker panel and cardiac troponin T in marathon runners before and after the 2005 Boston marathon. , 2006, American journal of clinical pathology.

[21]  Manfred Herrmann,et al.  Release of Glial Tissue–Specific Proteins After Acute Stroke: A Comparative Analysis of Serum Concentrations of Protein S-100B and Glial Fibrillary Acidic Protein , 2000, Stroke.

[22]  D. Laskowitz,et al.  Early biomarkers of stroke. , 2003, Clinical chemistry.

[23]  T. Neumann-Haefelin,et al.  Serum glial fibrillary acidic protein as a biomarker for intracerebral haemorrhage in patients with acute stroke , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[24]  Adnan I. Qureshi,et al.  Guidelines for the Early Management of Adults With Ischemic Stroke , 2007 .

[25]  J. Serena,et al.  Plasma Metalloproteinase-9 Concentration Predicts Hemorrhagic Transformation in Acute Ischemic Stroke , 2003, Stroke.

[26]  U. Dirnagl,et al.  Central nervous system injury-induced immune deficiency syndrome , 2005, Nature Reviews Neuroscience.

[27]  H. Steinmetz,et al.  Serum GFAP is a diagnostic marker for glioblastoma multiforme. , 2007, Brain : a journal of neurology.

[28]  David F. Moore,et al.  Using Peripheral Blood Mononuclear Cells to Determine a Gene Expression Profile of Acute Ischemic Stroke: A Pilot Investigation , 2005, Circulation.

[29]  J. Montaner,et al.  Pretreatment Hemostatic Markers of Symptomatic Intracerebral Hemorrhage in Patients Treated With Tissue Plasminogen Activator , 2006, Stroke.

[30]  J. Serena,et al.  Applicability of Biomarkers in Ischemic Stroke , 2007, Cerebrovascular Diseases.

[31]  A. Skoromets,et al.  Blood test detecting autoantibodies to N-methyl-D-aspartate neuroreceptors for evaluation of patients with transient ischemic attack and stroke. , 2003, Clinical chemistry.

[32]  J. Arenillas,et al.  Admission Fibrinolytic Profile Is Associated With Symptomatic Hemorrhagic Transformation in Stroke Patients Treated With Tissue Plasminogen Activator , 2004, Stroke.

[33]  Sergio E. Baranzini,et al.  Proteomic analysis of active multiple sclerosis lesions reveals therapeutic targets , 2008, Nature.

[34]  Jean-Charles Sanchez,et al.  PARK7 and nucleoside diphosphate kinase A as plasma markers for the early diagnosis of stroke. , 2005, Clinical chemistry.

[35]  Jin-Moo Lee,et al.  Identification of novel brain biomarkers. , 2006, Clinical chemistry.

[36]  Joseph P. Broderick,et al.  Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. , 1995 .

[37]  J. Arenillas,et al.  Matrix Metalloproteinase-9 Pretreatment Level Predicts Intracranial Hemorrhagic Complications After Thrombolysis in Human Stroke , 2003, Circulation.

[38]  G. Donnan,et al.  Neuroimaging, the ischaemic penumbra, and selection of patients for acute stroke therapy , 2002, The Lancet Neurology.

[39]  S. Kasner,et al.  Clinical Usefulness of a Biomarker-Based Diagnostic Test for Acute Stroke: The Biomarker Rapid Assessment in Ischemic Injury (BRAIN) Study , 2009, Stroke.

[40]  K. Furie,et al.  Mechanisms of Hemorrhagic Transformation After Tissue Plasminogen Activator Reperfusion Therapy for Ischemic Stroke , 2004, Stroke.

[41]  M. Luby,et al.  Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison , 2007, The Lancet.

[42]  S. Pedraza,et al.  Plasma Cellular-Fibronectin Concentration Predicts Hemorrhagic Transformation After Thrombolytic Therapy in Acute Ischemic Stroke , 2004, Stroke.