title: Early biomarkers of clinical-diffusion mismatch in acute ischemic stroke.
abstract: OBJECTIVE
  Clinical-diffusion mismatch (CDM; National Institutes of Health Stroke Scale score≥8 and diffusion-weighted imaging lesion volume<25 mL) has been suggested as a surrogate of ischemic brain at risk of infarction and might be used to recognize salvageable ischemic tissue. Our aim was to identify early biomarkers associated with the presence of CDM.
  
  
  METHODS
  We prospectively evaluated CDM in 226 patients (71.6±11.1 years, 58% men) with hemispheric ischemic stroke within 12 hours from symptom onset (median, 3.6 hours). Diffusion-weighted MRI lesion volume was measured by manual segmentation method. Serum levels of glutamate, aspartate, interleukin-10, tumor necrosis factor-α, interleukin-6, S100β, neuron-specific enolase, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, active matrix metalloproteinase-9, and cellular fibronectin were determined by immunoassay or high-performance liquid chromatography techniques in blood samples obtained at admission.
  
  
  RESULTS
  CDM was found in 61 patients (26.9%). Patients with CDM had higher serum levels of interleukin-10, tumor necrosis factor-α, and glutamate and lower serum levels of neuron-specific enolase, interleukin-6, and active matrix metalloproteinase-9 (all P<0.0001). Binary logistic regression showed that tumor necrosis factor-α≥21 pg/mL (OR, 21), glutamate≥230 μmol/L (OR, 27), neuron-specific enolase≥23 ng/mL (OR, 0.05), interleukin-6≥10 pg/mL (OR, 0.06), and active matrix metalloproteinase-9≥21 ng/mL (OR, 0.28) were independent molecular predictors of CDM after adjustment for covariates. The association of interleukin-10≥23 pg/mL and glutamate≥230 μmol/L levels predicted CDM with a sensitivity of 96% and a specificity of 98%.
  
  
  CONCLUSIONS
  High levels of interleukin-10, tumor necrosis factor-α, and glutamate as well as low levels of neuron-specific enolase, interleukin-6, and active matrix metalloproteinase-9 are associated with CDM.
authors.affiliation: Neurovascular ARea, Department of Neurology, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, University of Santiago de Comostela, Santiago de Compostela, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Rodríguez-Yáñez
authors.forename: Tomás
authors.initials: T
authors.lastname: Sobrino
authors.forename: Susana
authors.initials: S
authors.lastname: Arias
authors.forename: Fernando
authors.initials: F
authors.lastname: Vázquez-Herrero
authors.forename: David
authors.initials: D
authors.lastname: Brea
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanco
authors.forename: Rogelio
authors.initials: R
authors.lastname: Leira
authors.forename: Mar
authors.initials: M
authors.lastname: Castellanos
authors.forename: Joaquín
authors.initials: J
authors.lastname: Serena
authors.forename: José
authors.initials: J
authors.lastname: Vivancos
authors.forename: Antonio
authors.initials: A
authors.lastname: Dávalos
authors.forename: José
authors.initials: J
authors.lastname: Castillo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood*; D002545:Brain Ischemia / Q000097:blood* / Q000473:pathology; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D018698:Glutamic Acid / Q000097:blood; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000097:blood; D011446:Prospective Studies; D020521:Stroke / Q000097:blood* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D018698:Glutamic Acid; D020780:Matrix Metalloproteinase 9; D010751:Phosphopyruvate Hydratase