Clinical Pediatric Emergency Medicine
Volume 7, Issue 3 , Pages 186-193 , September 2006

The Use of Biomarkers After Inflicted Traumatic Brain Injury: Insight into Etiology, Pathophysiology, and Biochemistry

  • Rachel Pardes Berger, MD, MPH

      Affiliations

    • Department of Pediatrics, Children's Hospital of Pittsburgh, Pittsburgh, PA
    • Corresponding Author InformationReprint requests and correspondence: Rachel Berger MD, MPH, Children's Hospital of Pittsburgh, 3705 Fifth Avenue, Pittsburgh, PA 15213.
  • ,
  • Kent Hymel, MD

      Affiliations

    • Department of Pediatrics, Inova Fairfax Hospital for Children, Falls Church, VA
  • ,
  • Wei-Min Gao, MD, PhD

      Affiliations

    • The Institute of Environmental and Human Health, Texas Tech University, Lubbock, TX

References 

  1. DiScala C, Osberg J, Savage R. Children hospitalized for traumatic brain injury: transition to postacute care. J Head Trauma Rehab. 1997;12:1–10
  2. Overpeck MD, Brenner RA, Trumble AC, et al. Risk factors for infant homicide in the United States. N Engl J Med. 1998;339:1211–1216
  3. Keenan HT, Runyan DK, Marshall SW, et al. A population-based study of inflicted traumatic brain injury in young children. JAMA. 2003;290:621–626
  4. Makaroff KL, Putnam FW. Outcomes of infants and children with inflicted traumatic brain injury. Dev Med Child Neurol. 2003;45:497–502
  5. Keenan HT, Runyan DK, Nocera M. Child outcomes and family characteristics 1 year after severe inflicted or noninflicted traumatic brain injury. Pediatrics. 2006;117:317–324
  6. Beers S, Berger R, Skold A, et al. Neurocognitive outcome and relationship to serum markers in infants and young children following inflicted vs. noninflicted traumatic brain injury. Pediatr Res. 2004;55:70;[abst]
  7. Reece RM, Sege R. Childhood head injuries: accidental or inflicted?. Arch Pediatr Adolesc Med. 2000;154:11–15
  8. Duhaime AC, Alario AJ, Lewander WJ, et al. Head injury in very young children: mechanisms, injury types, and ophthalmologic findings in 100 hospitalized patients younger than 2 years of age. Pediatrics. 1992;90:179–185
  9. Jenny C, Hymel KP, Ritzen A, et al. Analysis of missed cases of abusive head trauma. JAMA. 1999;281:621–626
  10. Hymel KP, Hall CA. Diagnosing pediatric head trauma. Pediatr Ann. 2005;34:358–370
  11. Morris MW, Smith S, Cressman J, et al. Evaluation of infants with subdural hematoma who lack external evidence of abuse. Pediatrics. 2000;105:549–553
  12. Haviland J, Russell RI. Outcome after severe non-accidental head injury. Arch Dis Child. 1997;77:504–507
  13. Greenes DS, Schutzman SA. Occult intracranial injury in infants. Ann Emerg Med. 1998;32:680–686
  14. Ewing-Cobbs L, Kramer L, Prasad M, et al. Neuroimaging, physical, and developmental findings after inflicted and noninflicted traumatic brain injury in young children. Pediatrics. 1998;102:300–307
  15. Pitetti RD, Maffei F, Chang K, et al. Prevalence of retinal hemorrhages and child abuse in children who present with an apparent life-threatening event. Pediatrics. 2002;110:557–562
  16. Reece R. Treatment of child abuse: common ground for mental health, medical, and legal practitioners. Baltimore: Johns Hopkins University Press; 2000;
  17. Morad Y, Kim YM, Mian M, et al. Nonophthalmologist accuracy in diagnosing retinal hemorrhages in the shaken baby syndrome. J Pediatr. 2003;142:431–434
  18. Lewandrowski K, Chen A, Januzzi J. Cardiac markers for myocardial infarction. A brief review. Am J Clin Pathol. 2002;118(Suppl):S93–S99
  19. Thomas DG, Palfreyman JW, Ratcliffe JG. Serum-myelin-basic-protein assay in diagnosis and prognosis of patients with head injury. Lancet. 1978;1:113–115
  20. Hans P, Born JD, Chapelle JP, et al. Creatine kinase isoenzymes in severe head injury. J Neurosurg. 1983;58:689–692
  21. Kochanek PM, Clark RS, Ruppel RA, et al. Biochemical, cellular, and molecular mechanisms in the evolution of secondary damage after severe traumatic brain injury in infants and children: lessons learned from the bedside. Pediatr Crit Care Med. 2000;1:4–19
  22. Ruppel RA, Kochanek PM, Adelson PD, et al. Excitatory amino acid concentrations in ventricular cerebrospinal fluid after severe traumatic brain injury in infants and children: the role of child abuse. J Pediatr. 2001;138:18–25
  23. Nygren De Boussard C, Fredman P, Lundin A, et al. S100 in mild traumatic brain injury. Brain Inj. 2004;18:671–683
  24. Berger RP, Adelson PD, Pierce MC, et al. Serum neuron-specific enolase, S100B, and myelin basic protein concentrations after inflicted and noninflicted traumatic brain injury in children. J Neurosurg. 2005;103:61–68
  25. Ingebrigtsen T, Romner B. Biochemical serum markers of traumatic brain injury. J Trauma. 2002;52:798–808
  26. Berger RP, Dulani T, Leventhal JM, et al. 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;117:325–332
  27. Vos PE, Lamers KJ, Hendriks JC, et al. Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury. Neurology. 2004;62:1303–1310
  28. Berger RP. The use of serum biomarkers to predict outcome after traumatic brain injury in adults and children. J Head Trauma Rehab. 2006;in press
  29. Xiong Z, O'Hanlon D, Becker LE, et al. Enhanced calcium transients in glial cells in neonatal cerebellar cultures derived from S100B null mice. Exp Cell Res. 2000;257:281–289
  30. Nishiyama H, Knopfel T, Endo S, et al. Glial protein S100B modulates long-term neuronal synaptic plasticity. Proc Natl Acad Sci. 2002;99:4037–4042
  31. Ingebrigtsen T, Romner B, Marup-Jensen S, et al. The clinical value of serum S-100 protein measurements in minor head injury: a Scandinavian multicentre study. Brain Inj. 2000;14:1047–1055
  32. Anderson RE, Hansson LO, Nilsson O, et al. Increase in serum S100A1-B and S100B during cardiac surgery arises from extracerebral sources. Ann Thorac Surg. 2001;71:1512–1517
  33. Anderson RE, Hansson LO, Nilsson O, et al. High serum S100B levels for trauma patients without head injuries. Neurosurgery. 2001;48:1255–1260
  34. Romner B, Ingebrigtsen T. High serum S100B levels for trauma patients without head injuries. Neurosurgery. 2001;49:1490–1493
  35. Rothoerl RD, Woertgen C. High serum S100B levels for trauma patients without head injuries. Neurosurgery. 2001;49:1490–1493
  36. McKeating EG, Andrews PJ, Mascia L. Relationship of neuron specific enolase and protein S-100 concentrations in systemic and jugular venous serum to injury severity and outcome after traumatic brain injury. Acta Neurochir Suppl (Wien). 1998;71:117–119
  37. Berger R. Biomarkers or neuroimaging in central nervous system injury: will the real “gold standard” please stand up?. Pediatr Crit Care Med. 2003;4:391–392
  38. Yamazaki Y, Yada K, Morii S, et al. Diagnostic significance of serum neuron-specific enolase and myelin basic protein assay in patients with acute head injury. Surg Neurol. 1995;43:267–271
  39. National Institutes of Health. Apnea and home monitoring: report of a consensus development conference. Bethesda, (MA): U.S. Department of Health and Human Services; 1986;
  40. Bandyopadhyay S, Hennes H, Lo S. Role of serum biochemical markers in identifying inflicted traumatic brain injury in young infants. PAS. 2005;57:1867;(abst)
  41. Johnson DL, Boal D, Baule R. Role of apnea in nonaccidental head injury. Pediatr Neurosurg. 1995;23:305–310
  42. Starling SP, Patel S, Burke BL, et al. Analysis of perpetrator admissions to inflicted traumatic brain injury in children. Arch Pediatr Adolesc Med. 2004;158:454–458
  43. Ewing-Cobbs L, Prasad M, Kramer L, et al. Acute neuroradiologic findings in young children with inflicted or noninflicted traumatic brain injury. Childs Nerv Syst. 2000;16:25–34
  44. Rao P, Carty H, Pierce A. The acute reversal sign: comparison of medical and non-accidental injury patients. Clin Radiol. 1999;54:495–501
  45. Geddes JF, Hackshaw AK, Vowles GH, et al. Neuropathology of inflicted head injury in children. I. Patterns of brain damage. Brain. 2001;124:1290–1298
  46. Heindl UT, Laub MC. Outcome of persistent vegetative state following hypoxic or traumatic brain injury in children and adolescents. Neuropediatrics. 1996;27:94–100
  47. Bell MJ, Kochanek PM, Heyes MP, et al. Quinolinic acid in the cerebrospinal fluid of children after traumatic brain injury. Crit Care Med. 1999;27:493–497
  48. Berger RP, Heyes MP, Wisniewski SR, et al. Assessment of the macrophage marker quinolinic acid in cerebrospinal fluid after pediatric traumatic brain injury: insight into the timing and severity of injury in child abuse. J Neurotrauma. 2004;21:1123–1130
  49. Clark RS, Kochanek PM, Adelson PD, et al. Increases in bcl-2 protein in cerebrospinal fluid and evidence for programmed cell death in infants and children after severe traumatic brain injury. J Pediatr. 2000;137:197–204
  50. Satchell MA, Lai Y, Kochanek PM, et al. Cytochrome c, a biomarker of apoptosis, is increased in cerebrospinal fluid from infants with inflicted brain injury from child abuse. J Cereb Blood Flow Metab. 2005;25:919–927
  51. Berger RP, Pierce MC, Wisniewski SR, et al. Neuron-specific enolase and S100B in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatrics. 2002;109:E31
  52. Berger R, Adelson P, Richichi R, et al. Serum biomarkers after traumatic and hypoxemic brain injuries: insight into the biochemical response of the pediatric brain to inflicted brain injury. Devt Neuroscience. 2006;[in press]
  53. Hymel KP. Inflicted traumatic brain injury in infants and young children. Infants Young Child. 2002;15:57–65
  54. Bazarian J. Predicting post concussion syndrome after mild traumatic brain injury using serum S100B and cleaved-tau. Acad Emerg Med. 2004;11:516;[abst]
  55. Petzold A, Green AJ, Keir G, et al. Role of serum S100B as an early predictor of high intracranial pressure and mortality in brain injury: a pilot study. Crit Care Med. 2002;30:2705–2710
  56. Spinella PC, Dominguez T, Drott HR, et al. S-100beta protein-serum levels in healthy children and its association with outcome in pediatric traumatic brain injury. Crit Care Med. 2003;31:939–945
  57. Bandyopadhyay S, Hennes H, Gorelick MH, et al. Serum neuron-specific enolase as a predictor of short-term outcome in children with closed traumatic brain injury. Acad Emerg Med. 2005;12:732–738
  58. Wiesman D, Beers S, Richichi R, et al. Increased serum biomarker concentrations predict poor outcome after pediatric traumatic brain injury. PAS. 2006;59:4335;[abst]
  59. Gao WM, Chadha MS, Berger RP, et al. A gel-based proteomic comparison of human cerebrospinal fluid between inflicted and non-inflicted pediatric traumatic brain injury: a potential window to novel diagnostic biomarkers. J Neurotrauma. 2005;22:1212;[abst]
  60. Hochstrasser DF, Sanchez JC, Appel RD. Proteomics and its trends facing nature's complexity. Proteomics. 2002;2:807–812
  61. Davidsson P, Paulson L, Hesse C, et al. Proteome studies of human cerebrospinal fluid and brain tissue using a preparative two-dimensional electrophoresis approach prior to mass spectrometry. Proteomics. 2001;1:444–452
  62. Raymackers J, Daniels A, De Brabandere V, et al. Identification of two-dimensionally separated human cerebrospinal fluid proteins by N-terminal sequencing, matrix-assisted laser desorption/ionization-mass spectrometry, nanoliquid chromatography-electrospray ionization-time of flight-mass spectrometry, and tandem mass spectrometry. Electrophoresis. 2000;21:2266–2283
  63. Omenn GS, States DJ, Adamski M, et al. Overview of the HUPO Plasma Proteome Project: results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly-available database. Proteomics. 2005;5:3226–3245
  64. Wagner KR, Lindberg DM, Makoroff K, et al. Plasma biomarkers in shaken baby syndrome. In: 4th International Conference on Biochemical Markers for Brain Damage. 2005;p. 128;[abst]
  65. Campbell K, Berger R, Roberts M. Detecting inflicted traumatic brain injury: a cost-effective analysis. PAS. 2006;59:2912.437;[abst]
  66. Ruppel R, Kochanek P, Adelson P, et al. Excitotoxicity after severe traumatic brain injury in infants and children: the role of child abuse. J Pediatr. 2001;138:18–25
  67. Whalen MJ, Carlos TM, Kochanek PM, et al. Soluble adhesion molecules in CSF are increased in children with severe head injury. J Neurotrauma. 1998;15:777–787
  68. Amick J, Yandora K, Bell M, et al. The Th1 vs Th2 cytokine profile in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatr Crit Care Med. 2001;2:260–264
  69. Bell M, Kochanek P, Doughty L, et al. Interleukin-6 and interleukin-10 in cerebrospinal fluid after severe traumatic brain injury in children. J Neurotrauma. 1997;14:451–457
  70. Whalen MJ, Carlos TM, Kochanek PM, et al. Interleukin-8 is increased in cerebrospinal fluid of children with severe head injury. Crit Care Med. 2000;28:929–934
  71. Robertson CL, Bell MJ, Kochanek PM, et al. Increased adenosine in cerebrospinal fluid after severe traumatic brain injury in infants and children: association with severity of injury and excitotoxicity. Crit Care Med. 2001;29:2287–2293
  72. Han YY, Doughty LA, Kofos D, et al. Procalcitonin is persistently increased among children with poor outcome from bacterial sepsis. Pediatr Crit Care Med. 2003;4:21–25

PII: S1522-8401(06)00044-9

doi: 10.1016/j.cpem.2006.06.001

Clinical Pediatric Emergency Medicine
Volume 7, Issue 3 , Pages 186-193 , September 2006