Early Biomarkers of Clinical–Diffusion Mismatch in Acute Ischemic Stroke

Abstract

Background and Purpose— 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.