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.
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