These are exciting times as a blood test for traumatic brain injury is on the horizon. This R01 competitive renewal is a large scale validation study that will extend the work we have done on serum biomarkers in adults to children and youth, previously understudied groups. This proposal will systematically validate the diagnostic and prognostic ability of well-studied serum protein biomarkers and promising microRNA serum biomarkers in children and youth with mild traumatic brain injury (MTBI) and concussion. The biomarkers being proposed here have been studied in adults in data published by our group. Moreover, we will be examining promising microRNA biomarkers that we have evaluated in recently published pilot work. Patients will be enrolled from the emergency departments of adult and pediatric Level 1 Trauma Centers.
Our first aim i s will assess the brain-specificity of candidate biomarkers in determining presence of MTBI/concussion versus other traumatic injuries and head trauma without symptoms, as well as determining baseline levels by age and gender in uninjured children and youth. Being able to distinguish someone with and without a concussion would be so helpful, especially in children who cannot talk yet or with conditions such as autism spectrum disorders who cannot express themselves.
Our second aim will assess the diagnostic performance of candidate biomarkers in detecting critical injuries such as intracranial lesions on CT scan and acute neurological complications and will compare biomarker performance to validated clinical decision rules. This could potentially help reduce the number of CT scans done on children and reduce their exposure to ionizing radiation. Our third and final aim will assess the prognostic utility of serially measured biomarkers over six months in determining impairment or problems functioning. It will also help us understand the pattern of biomarker release over time in children and youth as it relates to recovery from injury. The goal of this research is to improve the clinical care of children and youth with MTBI and concussion by early recognition of injury and clinically validating a panel of blood- based markers (blood test) that could be used by clinicians in the acute, subacute, and chronic phases of injury to determine the need for diagnostic imaging (CT or MRI), acute neurological complications, specialized rehabilitation, or long-term risk for neurocognitive impairment. Ultimately, we hope the results of the proposal will change clinical practice by providing medical professional with more sensitive tools to detect brain injury and help patients and their families better understand their injury and recovery.
PUBLIC HEALTH RELEVANCE STATEMENT The goal of this research is to improve the clinical care of children and youth with mild traumatic brain injury and concussion by recognizing how severe their head injury is through a blood test. The blood test would look for substances released from the brain into the blood that could be used at different times after injury to help decide whether more diagnostic testing (like CT or MRI) is needed or if the patient will need neurosurgery or specialized rehabilitation. Ultimately, we hope the results of this study will change the way we treat children and youth with concussion by providing medical professionals with more sensitive tools to detect brain injury and help patients and their families better understand their injury and recovery.
|Papa, Linda; Mittal, Manoj K; Ramirez, Jose et al. (2017) Neuronal Biomarker Ubiquitin C-Terminal Hydrolase Detects Traumatic Intracranial Lesions on Computed Tomography in Children and Youth with Mild Traumatic Brain Injury. J Neurotrauma 34:2132-2140|
|Papa, Linda; Mittal, Manoj K; Ramirez, Jose et al. (2016) In Children and Youth with Mild and Moderate Traumatic Brain Injury, Glial Fibrillary Acidic Protein Out-Performs S100? in Detecting Traumatic Intracranial Lesions on Computed Tomography. J Neurotrauma 33:58-64|
|Papa, Linda; Brophy, Gretchen M; Welch, Robert D et al. (2016) Time Course and Diagnostic Accuracy of Glial and Neuronal Blood Biomarkers GFAP and UCH-L1 in a Large Cohort of Trauma Patients With and Without Mild Traumatic Brain Injury. JAMA Neurol 73:551-60|
|Papa, Linda (2016) Potential Blood-based Biomarkers for Concussion. Sports Med Arthrosc Rev 24:108-15|
|Papa, Linda; Ramia, Michelle M; Edwards, Damyan et al. (2015) Systematic review of clinical studies examining biomarkers of brain injury in athletes after sports-related concussion. J Neurotrauma 32:661-73|
|Papa, Linda; Zonfrillo, Mark R; Ramirez, Jose et al. (2015) Performance of Glial Fibrillary Acidic Protein in Detecting Traumatic Intracranial Lesions on Computed Tomography in Children and Youth With Mild Head Trauma. Acad Emerg Med 22:1274-82|
|Papa, Linda; Silvestri, Salvatore; Brophy, Gretchen M et al. (2014) GFAP out-performs S100? in detecting traumatic intracranial lesions on computed tomography in trauma patients with mild traumatic brain injury and those with extracranial lesions. J Neurotrauma 31:1815-22|
|Papa, Linda; Lewis, Lawrence M; Silvestri, Salvatore et al. (2012) Serum levels of ubiquitin C-terminal hydrolase distinguish mild traumatic brain injury from trauma controls and are elevated in mild and moderate traumatic brain injury patients with intracranial lesions and neurosurgical intervention. J Trauma Acute Care Surg 72:1335-44|
|Papa, Linda; Stiell, Ian G; Clement, Catherine M et al. (2012) Performance of the Canadian CT Head Rule and the New Orleans Criteria for predicting any traumatic intracranial injury on computed tomography in a United States Level I trauma center. Acad Emerg Med 19:2-10|
|Papa, Linda; Lewis, Lawrence M; Falk, Jay L et al. (2012) Elevated levels of serum glial fibrillary acidic protein breakdown products in mild and moderate traumatic brain injury are associated with intracranial lesions and neurosurgical intervention. Ann Emerg Med 59:471-83|
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