Department of Neurosurgery, Stanford University School of Medicine, Stanford, California, USA.
J Stroke Cerebrovasc Dis. 2012 Jan;21(1):30-41. doi: 10.1016/j.jstrokecerebrovasdis.2010.04.004. Epub 2010 Sep 19.
Currently, there are no established biomarkers for diagnosing preclinical vasospasm or monitoring its progression. Two areas of extensive biomarker research are neuroimaging and biochemical markers in body fluids, such as cerebrospinal fluid (CSF). We performed a review of studies conducted over the past 2 decades summarizing the science to date and the evolution of CSF biomarkers in subarachnoid hemorrhage (SAH). A Medline search performed using the search terms "subarachnoid hemorrhage marker AND cerebrospinal fluid," limited to the period January 1, 1990 to June 1, 2009, returned 62 references. Abstracts that did not deal primarily with SAH and potential markers in the CSF of humans were excluded, resulting in 27 abstracts. Only articles providing sufficient information for a substantiated analysis were selected. In addition, articles identified in reference lists of individual articles were selected if considered appropriate. Evidence was classified as class I-IV and recommendations were classified as category A-C according to European Federation of Neurological Societies guidelines. We evaluated CSF markers in SAH patients and divided them into 3 categories: A, markers with auspicious value; B, candidate markers; and C, noncandidate markers. Category A markers included tumor necrosis factor (TNF)-α, soluble tumor necrosis factor receptor I (sTNFR-I), and interleukin (IL)-1 receptor antagonist (IL-1ra), as well as the neurofilament proteins NFL and NfH. Category B markers included apolipoprotein E (ApoE), F2-isoprostane (F2-IsoP), NOx, and the indicators for thrombin activity membrane-bound tissue factor (mTF) and thrombin-antithrombin III complex (TAT) for neurologic outcome prediction, as well as E-selectin, lactate, alpha-II spectrin breakdown products (SBDPs), asymmetric dimethyl-L-arginine (ADMA), and monocyte chemoattractant protein-1 (MCP-1) for vasospasm prognostication. Category C markers included S100B, platelet-derived growth factor (PDGF), YKL-40, chitotriosidase, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and IL-8. Cytokines and their receptors, as well as neuronal intracellular proteins, seem to be potential markers for outcome determination in patients after SAH.
目前，还没有用于诊断临床前血管痉挛或监测其进展的既定生物标志物。生物标志物研究的两个主要领域是神经影像学和体液中的生化标志物，如脑脊液（CSF）。我们对过去 20 年进行的研究进行了综述，总结了迄今为止的科学进展以及蛛网膜下腔出血（SAH）中 CSF 标志物的演变。使用搜索词“蛛网膜下腔出血标志物 AND 脑脊液”在 Medline 上进行的搜索，仅限于 1990 年 1 月 1 日至 2009 年 6 月 1 日期间，返回了 62 个参考文献。排除了没有主要涉及 SAH 和人类 CSF 中潜在标志物的摘要，结果有 27 个摘要。只有提供充分分析依据的文章才被选中。此外，如果认为合适，还会选择个别文章参考文献列表中的文章。证据分为 I-IV 类，建议根据欧洲神经病学学会指南分为 A-C 类。我们评估了 SAH 患者的 CSF 标志物，并将其分为 3 类：A、有价值的标志物；B、候选标志物；C、非候选标志物。A 类标志物包括肿瘤坏死因子（TNF）-α、可溶性肿瘤坏死因子受体 I（sTNFR-I）和白细胞介素（IL）-1 受体拮抗剂（IL-1ra）以及神经丝蛋白 NFL 和 NfH。B 类标志物包括载脂蛋白 E（ApoE）、F2-异前列腺素（F2-IsoP）、NOx 以及凝血酶活性膜结合组织因子（mTF）和凝血酶抗凝血酶 III 复合物（TAT）等用于神经功能预后预测的指标，以及 E-选择素、乳酸、α-II spectrin 片段（SBDPs）、不对称二甲基-L-精氨酸（ADMA）和单核细胞趋化蛋白-1（MCP-1）用于预测血管痉挛。C 类标志物包括 S100B、血小板衍生生长因子（PDGF）、YKL-40、壳聚糖酶、细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）和白细胞介素-8。细胞因子及其受体以及神经元细胞内蛋白似乎是 SAH 后患者预后判断的潜在标志物。
