Exploring Serum Biomarkers for Mild Traumatic Brain Injury
Exploring Serum Biomarkers for Mild Traumatic Brain Injury
复制标题
探索轻度创伤性脑损伤的血清生物标志物
DOI：
10.1201/b18126-27
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发表时间：
2015
期刊：
影响因子：
64.8
通讯作者：
Michelle M. Ramia
中科院分区：
文献类型：
--
作者：
L. Papa;Damyan Edwards;Michelle M. Ramia
急性创伤性脑损伤（TBI）的诊断是基于神经学检查和神经成像工具，如CT扫描和MRI。然而，CT扫描对弥漫性脑损伤的敏感性较低，并且会暴露于辐射中。另一方面，MRI可以提供弥漫性损伤程度的信息，但其广泛应用受到成本的限制，许多中心MRI的可用性有限，以及在生理不稳定的患者中进行MRI的困难。虽然一些轻度创伤性脑损伤（mTBI）患者可能会住院过夜，但绝大多数患者在基本出院指示下接受治疗并从急诊科出院。这组TBI患者是准确诊断和预后预测的最大挑战。缺乏临床工具来检测影响日常功能的缺陷，使得这些人很少或根本没有治疗选择。这种损伤通常被认为“不严重”，随后也没有积极寻求MTBI的治疗方法。因此，在损伤后的早期阶段，TBI患者风险分层的诊断和预后工具是有限的。与其他基于器官的疾病不同，利用血液检测中的生物标志物进行快速诊断对于指导诊断和治疗是临床必不可少的，而TBI没有快速、明确的诊断血液检测。在过去的十年里，已经有无数的研究探索了许多有前途的生物标志物。尽管发表了大量的研究，但仍然缺乏任何fda批准的用于成人和儿童临床的生物标志物。现在有一个重要的需要来验证并将它们引入临床环境。本章将回顾一些在临床环境中被广泛研究的TBI生物标志物，重点是那些在MTBI中被评估的生物标志物。轻度创伤性脑损伤也被称为脑震荡，是对大脑的创伤性力量，导致大脑功能中断。这种破坏似乎是短暂的，但可能会产生持久的影响。它可以表现为精神状态的改变，如混乱、健忘症或意识丧失。许多人有一种误解，认为意识丧失一定是由mTBI或脑震荡引起的。因此，许多mTBI患者不寻求帮助，许多卫生保健专业人员也不认识到mTBI的发生。据估计，全球每年有1000万人受到脑外伤的影响（Hyder et al., 2007）。然而，考虑到许多患者维持mTBI但不寻求医疗护理，这可能被低估了。据世界卫生组织称，到2020年，脑外伤将超过许多疾病，成为导致死亡和残疾的主要原因（Hyder等人，2007年）。尽管根据格拉斯哥昏迷量表（GCS）评分，TBI通常分为轻度、中度和重度，但它实际上代表了一个损伤范围。GCS是一种15分的神经学量表，用于描述脑外伤的严重程度，最初旨在提供一种易于使用的评估工具，并促进轮班护理提供者之间的沟通（Teasdale和Jennett， 1974）。GCS等于或小于8被认为是“严重”TBI， GCS在9-12之间是“中度”TBI， GCS在13-15之间被认为是mTBI。“轻度创伤性脑损伤”这个词其实是用词不当。发生TBI且初始GCS评分为13-15分的个体具有颅内出血和弥漫性轴索损伤的急性风险（Stein et al., 2009）。此外，很大一部分人有身体、认知和心理功能受损的风险（Alexander, 1995； Alves等人，1993；Barth等人，1983；Millis等人，2001；Rimel等人，1981）。创伤性脑损伤的一个重要神经病理后果是轴突损伤，称为弥漫性轴突损伤（DAI），最近称为创伤性轴突损伤（TAI） （povlisshock, 1992）。DAI/TAI可发生在重度、中度和轻度脑外伤后，也可发生在机动车事故后可能发生的快速加速和减速力之后。DAI/TAI涉及许多异常，从轴突细胞骨架的直接损伤到运输中断、蛋白质水解和肿胀引起的继发性损伤（Johnson et al., 2012）。例如，离子失衡，通过钾的外流和钠的流入，导致钙流入细胞，造成线粒体损伤和乳酸生成的氧化代谢受损（Buki等人，2003年；Maxwell等人，2003年）。急性TBI的诊断是基于神经系统检查和神经成像工具，如计算机断层扫描（CT）和磁共振成像（MRI）。然而，CT扫描对弥漫性脑损伤的敏感性较低，并且会暴露于辐射中。MRI可以提供弥漫性损伤程度的信息，但其广泛应用受到成本的限制，许多中心MRI的可用性有限，以及在生理不稳定的患者中进行MRI的困难。特别是，DAI/TAI的识别更加困难，标准的神经成像技术可能无法检测到TBI （meeting et al., 2012）。弥散张量成像（DTI）是一种很有前途的神经成像技术，可能有助于识别mTBI后的轴突损伤（Bazarian et al., 2007; Huang et al., 2009）。然而，MRI和DTI在TBI患者急性临床管理中的作用尚未确立（Jagoda等，2008;Kesler, 2000）。虽然一些mTBI患者可能会住院过夜，但绝大多数患者在接受基本出院指示的情况下从急诊科接受治疗并出院。这组TBI患者是对准确诊断和预后预测的最大挑战。缺乏临床工具来检测影响日常功能的缺陷，使得这些人很少或根本没有治疗选择。这种损伤通常被认为“不严重”，随后也没有积极寻求mTBI的治疗方法。因此，在损伤后的早期阶段，TBI患者风险分层的诊断和预后工具是有限的。与其他基于器官的疾病（如心肌缺血或肾脏和肝脏功能障碍）不同，在临床上，利用血液检测中的生物标志物进行快速诊断对指导诊断和治疗至关重要，而TBI没有快速、明确的诊断血液检测。在过去的十年里，已经有无数的研究探索了许多有前途的生物标志物。尽管发表了大量的研究（Kochanek et al., 2008; Papa, 2012），但仍然缺乏任何食品和药物管理局批准的用于成人和儿童临床使用的生物标志物（Papa, 2012; Papa et al., 2013）。现在迫切需要验证它们并将其引入临床环境。本章将回顾一些在临床环境中被广泛研究的TBI生物标志物，重点是那些已经被mTBI评估的生物标志物。图22.1显示了将要回顾的生物标志物的神经解剖学位置。
The diagnosis of traumatic brain injury (TBI) in the acute setting is based on neurological examination and neuroimaging tools such as CT scanning and MRI. However, CT scanning has low sensitivity to diffuse brain damage and confers exposure to radiation. On the other hand, MRI can provide information on the extent of diffuse injuries but its widespread application is restricted by cost, the limited availability of MRI in many centers, and the difficulty of performing it in physiologically unstable patients. Although some patients with Mild traumatic brain injury (mTBI) may be admitted to the hospital overnight, the vast majority are treated and released from emergency departments with basic discharge instructions. This group of TBI patients represents the greatest challenges to accurate diagnosis and outcome prediction. The lack of clinical tools to detect the deficits that affect daily function, have left these individuals with little or no treatment options. The injury is often seen as “not severe” and subsequently therapies have not been aggressively sought for MTBI. The diagnostic and prognostic tools for risk stratification of TBI patients are therefore limited in the early stages after injury. Unlike other organ-based diseases where rapid diagnosis employing biomarkers from blood tests are clinically essential to guide diagnosis and treatment, there are no rapid, definitive diagnostic blood tests for TBI. Over the last decade there has been a myriad of studies exploring many promising biomarkers. Despite the large number of published studies there is still a lack of any FDA-approved biomarkers for clinical use in adults and children. There is now an important need to validate and introduce them into the clinical setting. This chapter will review some of the most widely studied biomarkers for TBI in the clinical setting, with an emphasis on those that have been evaluated in MTBI.Mild traumatic brain injury is also known as a concussion and is a traumatic force to the brain leading to a disruption of brain function. This disruption may seem transient, but could have long-lasting effects. It can manifest as an alteration in mental status such as confusion, amnesia, or loss of consciousness. There is a misconception among many that loss of consciousness must occur to have mTBI or concussion. As a result, many people with mTBI do not seek help, and many health care professionals do not recognize that an mTBI has occurred. There are an estimated 10 million people affected annually by TBI across the globe (Hyder et al., 2007). However, this is likely an underestimate given that many patients sustain mTBI but do not seek medical care. According to the World Health Organization, TBI will surpass many diseases as the major cause of death and disability by the year 2020 (Hyder et al., 2007).Although TBI is often categorized into mild, moderate, and severe based on the Glasgow Coma Scale (GCS) score, it really represents a spectrum of injury. The GCS is a 15-point neurological scale used to characterize severity of TBI and was originally intended to provide an easy-to-use assessment tool and to facilitate communication between care providers on rotating shifts (Teasdale and Jennett, 1974). A GCS equal to or less than 8 is considered a “severe” TBI, a GCS of 9–12 is a “moderate” TBI, and a GCS of 13–15 is considered mTBI. The term “mild TBI” is actually a misnomer. Individuals who incur a TBI and have an initial GCS score of 13–15 are acutely at risk for intracranial bleeding and diffuse axonal injury (Stein et al., 2009). Additionally, a significant proportion is at risk for impairment of physical, cognitive, and psychosocial functioning (Alexander, 1995; Alves et al., 1993; Barth et al., 1983; Millis et al., 2001; Rimel et al., 1981).An important neuropathological consequence of TBI is axonal injury, termed diffuse axonal injury (DAI) and more recently called traumatic axonal injury (TAI) (Povlishock, 1992). DAI/TAI can be found after severe, moderate, and mild TBI, and can occur after rapid acceleration and deceleration forces that can occur following motor vehicle accidents. DAI/TAI involves a number of abnormalities from direct damage to the axonal cytoskeleton to secondary damage from disruption of transport, proteolysis, and swelling (Johnson et al., 2012). For instance, ionic imbalances, through an efflux of potassium and influx of sodium, lead to calcium influx into cells, creating mitochondrial damage and impaired oxidative metabolism with lactate production (Buki et al., 2003; Maxwell et al., 2003).The diagnosis of TBI in the acute setting is based on neurological examination and neuroimaging tools such as computed tomography (CT) scanning and magnetic resonance imaging (MRI). However, CT scanning has low sensitivity to diffuse brain damage and confers exposure to radiation. MRI can provide information on the extent of diffuse injuries, but its widespread application is restricted by cost, the limited availability of MRI in many centers, and the difficulty of performing it in physiologically unstable patients. In particular, the recognition of DAI/TAI is even more difficult and standard neuroimaging techniques may not detect TBI (Metting et al., 2012). Diffusion tensor imaging (DTI) is a promising neuroimaging technique that may help to identify axonal injury after mTBI (Bazarian et al., 2007; Huang et al., 2009). However, the role of MRI and DTI in the acute clinical management of TBI patients has not been established (Jagoda et al., 2008; Kesler, 2000). Although some patients with mTBI may be admitted to the hospital overnight, the vast majority are treated and released from emergency departments with basic discharge instructions. This group of TBI patients represents the greatest challenge to accurate diagnosis and outcome prediction. The lack of clinical tools to detect the deficits that affect daily function have left these individuals with little or no treatment options. The injury is often seen as “not severe” and subsequently therapies have not been aggressively sought for mTBI.The diagnostic and prognostic tools for risk stratification of TBI patients are therefore limited in the early stages after injury. Unlike other organ-based diseases in which rapid diagnosis employing biomarkers from blood tests are clinically essential to guide diagnosis and treatment, such as for myocardial ischemia or kidney and liver dysfunction, there are no rapid, definitive diagnostic blood tests for TBI. Over the past decade, there have been myriad studies exploring many promising biomarkers. Despite the large number of published studies (Kochanek et al., 2008; Papa, 2012), there is still a lack of any Food and Drug Administration–approved biomarkers for clinical use in adults and children (Papa, 2012; Papa et al., 2013). There is now a strong need to validate and introduce them into the clinical setting.This chapter will review some of the most widely studied biomarkers for TBI in the clinical setting, with an emphasis on those that have been evaluated with mTBI. Figure 22.1 shows the neuroanatomical locations of the biomarkers that will be reviewed.
影响因子：
3.2
作者：
TROJANOWSKI, JQ;SCHUCK, T;LEE, VMY
通讯作者：
LEE, VMY