Neurovascular ARea, Department of Neurology, Clinical Neurosciences Research Laboratory, Hospital Clínico Universitario, University of Santiago de Comostela, Santiago de Compostela, Spain.
Stroke. 2011 Oct;42(10):2813-8. doi: 10.1161/STROKEAHA.111.614503. Epub 2011 Aug 11.
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.
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.
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%.
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.
临床-弥散不匹配（CDM；美国国立卫生研究院卒中量表评分≥8 分且弥散加权成像病变体积＜25ml）已被认为是缺血性脑梗死风险的替代指标，可能用于识别可挽救的缺血组织。我们的目的是确定与 CDM 存在相关的早期生物标志物。
我们前瞻性评估了 226 例发病 12 小时内（中位数 3.6 小时）的半球性缺血性卒中患者的 CDM（71.6±11.1 岁，58%为男性）。通过手动分割方法测量弥散加权 MRI 病变体积。入院时采集血样，采用免疫测定或高效液相色谱技术测定血清谷氨酸、天门冬氨酸、白细胞介素-10、肿瘤坏死因子-α、白细胞介素-6、S100β、神经元特异性烯醇化酶、细胞间黏附分子-1、血管细胞黏附分子-1、活性基质金属蛋白酶-9 和细胞纤维连接蛋白水平。
61 例（26.9%）患者存在 CDM。CDM 患者的血清白细胞介素-10、肿瘤坏死因子-α和谷氨酸水平较高，神经元特异性烯醇化酶、白细胞介素-6和活性基质金属蛋白酶-9 水平较低（均 P＜0.0001）。二元逻辑回归显示，肿瘤坏死因子-α≥21pg/ml（OR，21）、谷氨酸≥230μmol/L（OR，27）、神经元特异性烯醇化酶≥23ng/ml（OR，0.05）、白细胞介素-6≥10pg/ml（OR，0.06）和活性基质金属蛋白酶-9≥21ng/ml（OR，0.28）是调整协变量后 CDM 的独立分子预测因子。白细胞介素-10≥23pg/ml 和谷氨酸≥230μmol/L 水平的联合预测 CDM 的敏感性为 96%，特异性为 98%。
高水平的白细胞介素-10、肿瘤坏死因子-α和谷氨酸以及低水平的神经元特异性烯醇化酶、白细胞介素-6和活性基质金属蛋白酶-9与 CDM 相关。
