title: Association of serial biochemical markers with acute ischemic stroke: the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Study.
abstract: OBJECTIVE
  Biochemical markers of acute neuronal injury may aid in the diagnosis and management of acute ischemic stroke. Serum samples from the National Institute for Neurological Disorders and Stroke (NINDS) recombinant tissue plasminogen activator Stroke Study were analyzed for the presence of 4 biochemical markers of neuronal, glial, and endothelial cell injury. These biochemical markers, myelin basic protein (MBP), neuron-specific enolase (NSE), S100beta, and soluble thrombomodulin, were studied for an association with initial stroke severity, infarct volume, and functional outcome.
  
  
  METHODS
  In the original NINDS study, serum samples were drawn from all patients on presentation to the Emergency Department and at approximately 2 and 24 hours after initiation of study therapy. In this analysis, stored serum samples were available for 359 patients; 107 patients had samples for all 3 time points. Serum marker concentrations were measured by ELISA techniques. We examined the relation between serum concentrations of each marker and the degree of baseline neurological deficit, functional outcome, and infarct size on computed tomography at 24 hours and the effect of fibrinolytic therapy.
  
  
  RESULTS
  Higher 24-hour peak concentrations of MBP, NSE, and S100beta were associated with higher National Institutes of Health Stroke Scale baseline scores (r=0.186, P<0.0001; r=0.117, P=0.032; and r=0.263, P<0.0001, respectively). Higher peak concentrations of MBP and S100beta (r=0.209, P<0.0001; r=0.239, P<0.0001) were associated with larger computed tomography lesion volumes. Patients with favorable outcomes had smaller changes in MBP and S100beta (P<0.05) concentrations in the first 24 hours. Soluble thrombomodulin was not associated with any severity or outcome measure.
  
  
  CONCLUSIONS
  This study corroborates previous work demonstrating correlations of MBP, NSE, and S100beta with clinical and radiographic features in acute stroke. Despite significantly better outcomes in the tissue plasminogen activator-treated group, we found no difference in the early release of the 4 biomarkers between treatment groups. Further study will define the role of biomarkers in acute stroke management and prognostication.
authors.affiliation: Department of Emergency Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267-0769, USA. edward.jauch@uc.edu
authors.forename: Edward C
authors.initials: EC
authors.lastname: Jauch
authors.forename: Christopher
authors.initials: C
authors.lastname: Lindsell
authors.forename: Joseph
authors.initials: J
authors.lastname: Broderick
authors.forename: Susan C
authors.initials: SC
authors.lastname: Fagan
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Tilley
authors.forename: Steven R
authors.initials: SR
authors.lastname: Levine
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001925:Brain Damage, Chronic / Q000097:blood / Q000209:etiology / Q000473:pathology; D020520:Brain Infarction / Q000000981:diagnostic imaging / Q000209:etiology / Q000473:pathology; D002545:Brain Ischemia / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D004311:Double-Blind Method; D042783:Endothelial Cells / Q000737:chemistry / Q000473:pathology; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D004676:Myelin Basic Protein / Q000097:blood*; D009414:Nerve Growth Factors / Q000097:blood*; D009457:Neuroglia / Q000737:chemistry / Q000473:pathology; D009474:Neurons / Q000737:chemistry / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000627:therapeutic use; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins / Q000097:blood*; D018180:Thrombomodulin / Q000097:blood*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005343:Fibrinolytic Agents; D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; D011994:Recombinant Proteins; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins; D018180:Thrombomodulin; D010959:Tissue Plasminogen Activator; D010751:Phosphopyruvate Hydratase