FRONTlines

The Newsletter of CIRCL, the Center for Injury Research & Control at the University of Pittsburgh

Volume 10, Issue 1: Spring 2007

Improving the Diagnosis and Prognosis of Inflicted Head Trauma in Infants

Inflicted traumatic brain injury (iTBI) -- also known as shaken baby syndrome -- is the leading cause of death from child abuse as well as the leading cause of death from traumatic brain injury in infants. Recognition of iTBI can be difficult; parents often do not provide a history of trauma, infants present with non-specific symptoms such as vomiting or fussiness that are seen in a variety of pediatric illnesses, and the physical examination can be normal. Accurate and timely diagnosis of iTBI is critical; infants with iTBI who are misdiagnosed are likely to return to a violent environment and be injured again or killed. The research of Dr. Patrick Kochanek and Dr. Rachel Berger has focused on trying to develop a screening tool for brain injury which would alert the treating physician to the possibility of a brain injury and the need for a head CT in an infant in whom trauma would not otherwise be suspected.

This CIRCL-funded research has focused on the use of serum and cerebrospinal fluid (CSF) biomarkers as screening tools for iTBI.  Dr. Kochanek and Dr. Berger recently published a prospective study evaluating the use of serum CSF as screening tools for iTBI in high-risk infants. (1) This study -- which was given a 2007 O.S.C.A.R (OutStanding Child Abuse Research) at the 2007 San Diego Conference on Child Maltreatment -- demonstrated that an increase in the concentration of either neuron-specific enolase (NSE) or myelin-basic protein (MBP) was 79% sensitive and 70% specific for iTBI. Based on the result of this study, a two-center, definitive prospective study was submitted to the National Institutes of Health as an R01 application in October 2006. If biomarkers are an effective screening tool for iTBI, they will be instrumental in decreasing the associated morbidity and mortality.

As part of the current and previously-funded CIRCL research, Dr. Kochanek and Dr. Berger have created a serum and CSF repository at the Safar Center for Resuscitation Research. These have allowed them and other researchers to conduct related studies examining the pathophysiology of iTBI. The January 2007 issue of the Journal of Neurotrauma contained a special compendium devoted to iTBI; Drs. Kochanek and Berger were co-editors of this edition and the Safar Center serum/CSF repository was the source of data for three of the peer-reviewed articles in the journal. (2-4) Drs. Berger and/or Kochanek were co-authors on each of these papers. A special edition of Developmental Neuroscience in 2006 was devoted to the topic of pediatric TBI. Dr. Kochanek authored the introduction to this journal (5) and Dr. Berger was the first author of one of the invited articles in the journal which compared the serum biomarker profile in children with iTBI, non-inflicted TBI (nTBI) and acute hypoxemia; the results suggest that biochemically, iTBI is more similar to acute hypoxemia than to nTBI. (6) These data are consistent with other radiologic, pathologic and clinical data and may have implications for treatment of iTBI. In addition to Dr. Berger’s article, three of the other full-length articles in this special edition used CSF from the Safar Center repository. (7-9)

Over the past 12 months, the data from CIRCL-funded research has been presented at multiple national and international conferences including the 16th Annual Pediatric Critical Care Colloquium, the 2007 Meeting of the Society of Neuroanesthesia and Critical Care Medicine, the 35th Congress of the Society of Critical Care Medicine, the 2006 North American Conference on Shaken Baby Syndrome and the 2007 San Diego Conference on Child Maltreatment as well as at Grand Rounds at Mt. Sinai Hospital in New York, Children's Hospital of Pittsburgh, Department of Physical Medicine and Rehabilitation at the University of Pittsburgh, and the Children’s Hospital and Harborview Hospital in Seattle, Washington.

References:

  1. Berger R, Dulani T, Leventhal JM, Richichi R, Kochanek P. Identification of inflicted traumatic brain injury in well-appearing infants using serum and cerebrospinal fluid markers: A possible screening tool for inflicted traumatic brain injury. Pediatrics 2006;117:325-32.
  2. Gao W, Chadha M, Berger R, et al. A gel-based proteomic comparison of human cerebrospinal fluid between inflicted and non-inflicted pediatric traumatic brain injury. J Neurotrauma 2007;24(1):43-53.
  3. Shore P, Berger R, Varma S, et al. Cerebrospinal fluid biomarkers versus Glasgow Coma Scale and Glasgow Outcome Scale in pediatric traumatic brain injury: The role of young age and inflicted injury. J Neurotrauma 2007;24(1):75-86.
  4. Beers S, Berger R, Adelson P. Neurocognitive outcome and serum biomarkers in inflicted vs non-inflicted traumatic brain injury in young children. J Neurotrauma 2007;24(1):97-105.
  5. Kochanek PM. Pediatric traumatic brain injury: quo vadis? Dev Neurosci 2006;28(4-5):244-255.
  6. Berger R, Adelson P, Richichi R, Kochanek P. Serum biomarkers after traumatic and hypoxemic brain injuries: Insight into the biochemical response of the pediatric brain to inflicted brain injury Dev Neurosci 2006;28(4-5):327-335.
  7. Lai Y, Stange C, Wisniewski SR, et al. Mitochondrial heat shock protein 60 is increased in cerebrospinal fluid following pediatric traumatic brain injury. Dev Neurosci 2006;28(4-5):336-341.
  8. Cousar JL, Lai Y, Marco CD, et al. Heme oxygenase 1 in cerebrospinal fluid from infants and children after severe traumatic brain injury. Dev Neurosci 2006;28(4-5):342-347.
  9. Bayir H, Kochanek PM, Kagan VE. Oxidative stress in immature brain after traumatic brain injury. Dev Neurosci 2006;28(4-5):420-431.

 

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