Senn Rebecca, Elkind Mitchell S V, Montaner Joan, Christ-Crain Mirjam, Katan Mira
Department of Endocrinology, University Hospital Basel, Basel, Switzerland.
Cerebrovasc Dis. 2014;38(6):395-409. doi: 10.1159/000366470. Epub 2014 Dec 3.
Intracerebral hemorrhage (ICH), a subtype of stroke associated with high mortality and disability, accounts for 13% of all strokes. Basic and clinical research has contributed to our understanding of the complex pathophysiology of neuronal injury in ICH. Outcome rates, however, remain stable, and questions regarding acute management of ICH remain unanswered. Newer research is aiming at matching measured levels of serum proteins, enzymes, or cells to different stages of brain damage, suggesting that blood biomarkers may assist in acute diagnosis, therapeutic decisions, and prognostication. This paper provides an overview on the most promising blood biomarkers and their potential role in the diagnosis and management of spontaneous ICH.
Information was collected from studies, reviews, and guidelines listed in PubMed up to November 2013 on blood biomarkers of nontraumatic ICH in humans. We describe the potential role and limitations of GFAP, S100B/RAGE, and ApoC-III as diagnostic biomarkers, β-Amyloid as a biomarker for etiological classification, and 27 biomarkers for prognosis of mortality and functional outcome. Within the group of prognostic markers we discuss markers involved in coagulation processes (e.g., D-Dimers), neuroendocrine markers (e.g., copeptin), systemic metabolic markers (e.g., blood glucose levels), markers of inflammation (e.g., IL-6), as well as growth factors (e.g., VEGF), and others (e.g., glutamate). Some of those blood biomarkers are agents of pathologic processes associated with hemorrhagic stroke but also other diseases, whereas others play more distinct pathophysiological roles and help in understanding the basic mechanisms of brain damage and/or recovery in ICH.
Numerous blood biomarkers are associated with different pathophysiological pathways in ICH, and some of them promise to be useful in the management of ICH, eventually contributing additional information to current tools for diagnosis, therapy monitoring, risk stratification, or intervention. Up to date, however, no blood biomarker of ICH has been studied sufficiently to find its way into clinical routine yet; well-designed, large-scale, clinical studies addressing relevant clinical questions are needed. We suggest that the effectiveness of biomarker research in ICH might be improved by international cooperation and shared resources for large validation studies, such as provided by the consortium on stroke biomarker research (http://stroke-biomarkers.com/page.php?title=Resources).
脑出血(ICH)是中风的一种亚型,死亡率和致残率高,占所有中风病例的13%。基础研究和临床研究有助于我们了解脑出血中神经元损伤的复杂病理生理学。然而,治疗效果仍保持稳定,关于脑出血急性处理的问题仍未得到解答。最新研究旨在将血清蛋白、酶或细胞的检测水平与脑损伤的不同阶段相匹配,这表明血液生物标志物可能有助于急性诊断、治疗决策和预后评估。本文概述了最具前景的血液生物标志物及其在自发性脑出血诊断和管理中的潜在作用。
从截至2013年11月PubMed上列出的关于人类非创伤性脑出血血液生物标志物的研究、综述和指南中收集信息。我们描述了胶质纤维酸性蛋白(GFAP)、S100B/晚期糖基化终产物受体(RAGE)和载脂蛋白C-III(ApoC-III)作为诊断生物标志物的潜在作用和局限性,β-淀粉样蛋白作为病因分类生物标志物的作用,以及27种用于死亡率和功能预后评估的生物标志物。在预后标志物组中,我们讨论了参与凝血过程的标志物(如D-二聚体)、神经内分泌标志物(如 copeptin)、全身代谢标志物(如血糖水平)、炎症标志物(如白细胞介素-6)、生长因子(如血管内皮生长因子)以及其他标志物(如谷氨酸)。其中一些血液生物标志物是与出血性中风以及其他疾病相关的病理过程的介质,而其他一些则发挥更独特的病理生理作用,有助于理解脑出血中脑损伤和/或恢复的基本机制。
众多血液生物标志物与脑出血中的不同病理生理途径相关,其中一些有望在脑出血管理中发挥作用,最终为当前的诊断、治疗监测、风险分层或干预工具提供更多信息。然而,迄今为止,尚无一种脑出血血液生物标志物得到充分研究以纳入临床常规;需要设计良好的大规模临床研究来解决相关临床问题。我们建议,通过国际合作和共享资源进行大型验证研究,如中风生物标志物研究联盟(http://stroke-biomarkers.com/page.php?title=Resources)提供的资源,可能会提高脑出血生物标志物研究的有效性。