Jauch Edward C, Lindsell Christopher, Broderick Joseph, Fagan Susan C, Tilley Barbara C, Levine Steven R
Department of Emergency Medicine, University of Cincinnati Medical Center, Cincinnati, OH 45267-0769, USA.
Stroke. 2006 Oct;37(10):2508-13. doi: 10.1161/01.STR.0000242290.01174.9e. Epub 2006 Sep 7.
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.
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.
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.
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.
急性神经元损伤的生化标志物可能有助于急性缺血性卒中的诊断与治疗。对美国国立神经疾病与卒中研究所（NINDS）重组组织型纤溶酶原激活剂卒中研究中的血清样本进行分析，以检测4种神经元、神经胶质和内皮细胞损伤的生化标志物。研究这些生化标志物，即髓鞘碱性蛋白（MBP）、神经元特异性烯醇化酶（NSE）、S100β和可溶性血栓调节蛋白，与初始卒中严重程度、梗死体积和功能转归之间的关联。
在原NINDS研究中，所有患者在就诊于急诊科时以及开始研究治疗后约2小时和24小时采集血清样本。在本次分析中，有359例患者的储存血清样本可用；107例患者在所有3个时间点均有样本。采用酶联免疫吸附测定（ELISA）技术测量血清标志物浓度。我们研究了每种标志物的血清浓度与基线神经功能缺损程度、功能转归以及24小时计算机断层扫描梗死灶大小之间的关系，以及纤溶治疗的效果。
MBP、NSE和S100β在24小时时的峰值浓度较高与美国国立卫生研究院卒中量表（NIHSS）基线评分较高相关（r分别为0.186，P<0.0001；r为0.117，P=0.032；r为0.263，P<0.0001）。MBP和S100β的峰值浓度较高（r分别为0.209，P<0.0001；r为0.239, P<0.0001）与计算机断层扫描病变体积较大相关。功能转归良好的患者在最初24小时内MBP和S100β浓度的变化较小（P<0.05）。可溶性血栓调节蛋白与任何严重程度或转归指标均无关联。
本研究证实了先前的研究结果，即MBP、NSE和S100β与急性卒中的临床和影像学特征相关。尽管组织型纤溶酶原激活剂治疗组的转归明显更好，但我们发现治疗组之间这4种生物标志物的早期释放没有差异。进一步的研究将明确生物标志物在急性卒中治疗和预后评估中的作用。
