Using Biochemical Markers to Detect Abusive Head Trauma

描述（由申请人提供）：虐待儿童是婴幼儿严重创伤性脑损伤（TBI）的主要原因。正确诊断虐待性头部创伤（AHT）是困难的，即使是经验丰富，精明的医生。误诊是常见的，可能会给病人带来灾难性的医疗后果。除了提高认识外，目前还没有既定的策略或诊断测试来帮助医生正确识别AHT。一种能够提醒医生注意AHT的可能性的筛查试验，从而有助于正确和及时的诊断，可能会产生巨大的影响。脑损伤后，脑损伤的生化标志物从脑中释放出来，扩散到脑脊液（CSF）和/或血清中，在那里可以测量它们的浓度。脑脊液和血清中三种生化标志物——神经元特异性烯醇化酶（NSE）、S100B和髓鞘碱性蛋白（MBP）的浓度是成人和儿童轻度、中度和重度TBI的敏感指标。因此，这些标志物可能有潜力作为诊断辅助，以补充医生在正确诊断AHT时的敏锐度。特异性目的1是确定血清NSE浓度用于检测AHT风险增加的婴儿的敏感性和特异性，并确定与作为单一标志物的NSE相比，使用NSE、S100B和MBP是否能提高敏感性或特异性。特异性目的2是确定脑脊液和血清NSE、S100B和/或MBP的升高是TBI特异性的，还是它们的浓度是否会受到四种非创伤性神经损伤的影响：缺氧缺血性脑病、脑膜炎、进行性脑病和癫痫发作。候选人是匹兹堡儿童医院（CHP）的儿科医生。该指导职业发展奖将允许候选人在儿科神经创伤和儿童虐待方面进行独特且高度综合的指导项目。匹兹堡是开展这类项目的理想环境，因为这里有卫生防护中心、萨法尔复苏研究中心和儿童权益中心的资源。Patrick Kochanek博士是该奖项的主要导师，因其在儿科TBI领域的工作而获得国际认可，曾担任多个K奖的导师，并且是niched资助的儿科神经重症监护培训补助金（T32）的PI。

DESCRIPTION (provided by applicant): Child abuse is a leading cause of serious traumatic brain injury (TBI) in infants and young children. Proper diagnosis of abusive head trauma (AHT) is difficult even for experienced, astute physicians. Misdiagnosis is common and can have catastrophic medical consequences for patients. Aside from increased awareness, there are currently no established strategies or diagnostic tests to help physicians properly identify AHT. A screening test that could alert physicians to the possibility of AHT and thereby aid in proper and timely diagnosis, could have an enormous impact. Biochemical markers of brain injury are released from the brain after TBI and diffuse into cerebrospinal fluid (CSF) and/or serum, where their concentrations can be measured. CSF and serum concentrations of three of these biochemical markers -- neuron-specific enolase (NSE), S100B, and myelin-basic protein (MBP) - are sensitive indicators of mild, moderate and severe TBI in adults and children. These markers may therefore have the potential to act as diagnostic adjuncts to complement physician acumen in properly diagnosing AHT. Specific Aim 1 is to determine the sensitivity and specificity of serum NSE concentrations for detecting AHT in infants at increased risk of AHT and to determine whether the use of a panel of NSE, S100B and MBP improves sensitivity or specificity when compared with NSE as a single marker. Specific Aim 2 is to determine whether increases in CSF and serum NSE, S100B and/or MBP are specific to TBI or whether their concentrations can be affected by four non-traumatic neurological insults: hypoxic-ischemic encephalopathy, meningitis, progressive encephalopathy and seizures. The candidate is a pediatrician at Children's Hospital of Pittsburgh (CHP). This Mentored Career Development Award will allow the candidate to pursue a unique and highly integrated mentored program in pediatric neurotrauma and child abuse. Pittsburgh is an ideal environment for this type of program because of the resources of CHP, the Safar Center for Resuscitation Research and The Child Advocacy Center. Dr. Patrick Kochanek, the primary mentor for this award, is internationally recognized for his work in the field of pediatric TBI, has served as a mentor on multiple K awards and is the PI of an NICHD-funded training grant (T32) in pediatric neurointensive care.