nach oben

International Journal of Legal Medicine

Erschienen in:

01.01.2015 | Original Article

Encephalopathy and death in infants with abusive head trauma is due to hypoxic-ischemic injury following local brain trauma to vital brainstem centers

verfasst von: Jakob Matschke, Andreas Büttner, Markus Bergmann, Christian Hagel, Klaus Püschel, Markus Glatzel

Erschienen in: International Journal of Legal Medicine | Ausgabe 1/2015

Einloggen, um Zugang zu erhalten

Abstract

Background

Infants with abusive head trauma (AHT) have diffuse brain damage with potentially fatal brain swelling. The pathogenesis of the brain damage remains unclear. We hypothesize that brain damage in AHT is due to hypoxic-ischemic injury with hypoxic-ischemic encephalopathy (HIE) rather than primary traumatic brain injury (TBI) with traumatic diffuse axonal injury (tDAI).

Methods

We studied brain tissue of AHT victims. Primary outcome measure was the presence of primary traumatic versus hypoxic-ischemic brain injury. The diagnosis of tDAI followed a standardized semiquantitative diagnostic approach yielding a 4-tiered grading scheme (definite, possible, improbable, and none). In addition, results of quantitative immunohistochemical analysis in a subgroup of AHT victims with instant death were compared with matched SIDS controls.

Results

In our cohort of 50 AHT victims, none had definite tDAI (no tDAI in 30, tDAI possible in 2, and tDAI improbable in 18). Instead, all AHT victims showed morphological findings indicative of HIE. Furthermore, the subgroup with instant death showed significantly higher counts of damaged axons with accumulation of amyloid precursor protein (APP) in the brainstem adjacent to the central pattern generator of respiratory activity (CPG) (odds ratio adjusted for age, sex, brain weight, and APP-count in other regions = 3.1; 95 % confidence interval = 1.2 to 7.7; p = 0.015).

Conclusions

AHT victims in our cohort do not have diffuse TBI or tDAI. Instead, our findings indicate that the encephalopathy in AHT is the due to hypoxic-ischemic injury probably as the result of respiratory arrest due to local damage to parts of the CPG in the brainstem.

Nur mit Berechtigung zugänglich

Keenan HT (2010) Epidemiology of abusive head trauma. In: Jenny C (ed) Child abuse and neglect: diagnosis, treatment and evidence. Saunders, p. 35–39

Matschke J, Voss J, Obi N, Goerndt J, Sperhake JP, Pueschel K et al (2009) Nonaccidental head injury is the most common cause of subdural bleeding in infants <1 year of age. Pediatrics 124(6):1587–94CrossRefPubMed

Matschke J, Pueschel K, Glatzel M (2009) Ocular pathology in shaken baby syndrome and other forms of infantile non-accidental head injury. Int J Legal Med 123(3):189–97CrossRefPubMed

Sieswerda-Hoogendoorn T, Boos S, Spivack B, Bilo RAC, van Rijn RR (2012) Educational paper abusive head trauma Part I. Clinical aspects. Eur J Pediatr 171(3):415–23CrossRefPubMed

Barnes PD, Krasnokutsky M (2007) Imaging of the central nervous system in suspected or alleged nonaccidental injury, including the mimics. Top Magn Reson Imaging 18(1):53–74CrossRefPubMed

Geddes JF, Hackshaw AK, Vowles GH, Nickols CD, Whitwell HL (2001) Neuropathology of inflicted head injury in children. I. Patterns of brain damage. Brain 124(Pt 7):1290–8CrossRefPubMed

Geddes JF, Vowles GH, Hackshaw AK, Nickols CD, Scott IS, Whitwell HL (2001) Neuropathology of inflicted head injury in children. II. Microscopic brain injury in infants. Brain 124(Pt 7):1299–306CrossRefPubMed

Johnson DL, Boal D, Baule R (1995) Role of apnea in nonaccidental head injury. Pediatr Neurosurg 23(6):305–10CrossRefPubMed

Hadley MN, Sonntag VK, Rekate HL, Murphy A (1989) The infant whiplash-shake injury syndrome: a clinical and pathological study. Neurosurgery 24(4):536–40CrossRefPubMed

10.

Krous HF, Beckwith JB, Byard RW, Rognum TO, Bajanowski T, Corey T et al (2004) Sudden infant death syndrome and unclassified sudden infant deaths: a definitional and diagnostic approach. Pediatrics 114(1):234–8CrossRefPubMed

11.

Leestma JE (2009) Forensic neuropathology. CRC Press Taylor & Francis Group, Boca Raton

12.

Matschke J, Glatzel M (2008) Neuropathological assessment of non-accidental head injury in infants and toddlers. Rechtsmedizin 18(1):29–35CrossRef

13.

Matschke J, Glatzel M (2008) Ophthalmopathological aspects of the non-accidental head injury in infants and young children. Rechtsmedizin 18(1):36–41CrossRef

14.

Oehmichen M, Auer RN, König HG, Jellinger KA (2006) Forensic neuropathology and associated neurology. Springer, Berlin, 660 pCrossRef

15.

Itabashi HH, Andrews JM, Tomiyasu U (2007) Forensic neuropathology: a practical review of the fundamentals. Elsevier, 481 p

16.

Oehmichen M, Woetzel F, Meissner C (2009) Hypoxic-ischemic changes in SIDS brains as demonstrated by a reduction in MAP2-reactive neurons. Acta Neuropathol 117(3):267–74CrossRefPubMed

17.

Kühn J, Meissner C, Oehmichen M (2005) Microtubule-associated protein 2 (MAP2)—a promising approach to diagnosis of forensic types of hypoxia-ischemia. Acta Neuropathol 110(6):579–86CrossRefPubMed

18.

Shannon P, Smith CR, Deck J, Ang LC, Ho M, Becker L (1998) Axonal injury and the neuropathology of shaken baby syndrome. Acta Neuropathol 95(6):625–31CrossRefPubMed

19.

Oehmichen M, Meissner C, Schmidt V, Pedal I, König HG, Saternus KS (1998) Axonal injury—a diagnostic tool in forensic neuropathology? A review. Forensic Sci Int 95(1):67–83CrossRefPubMed

20.

Engel S, Schluesener H, Mittelbronn M, Seid K, Adjodah D, Wehner HD et al (2000) Dynamics of microglial activation after human traumatic brain injury are revealed by delayed expression of macrophage-related proteins MRP8 and MRP14. Acta Neuropathol 100(3):313–22CrossRefPubMed

21.

Streit WJ (1996) The role of microglia in brain injury. Neurotoxicology 17(3–4):671–8PubMed

22.

Loane DJ, Byrnes KR (2010) Role of microglia in neurotrauma. Neurotherapeutics 7(4):366–77CrossRefPubMedPubMedCentral

23.

Loane DJ, Kumar A, Stoica BA, Cabatbat R, Faden AI (2014) Progressive neurodegeneration after experimental brain trauma: Association with chronic microglial activation. J Neuropathol Exp Neurol 73(1):14–29CrossRefPubMed

24.

Dolinak D, Reichard R (2006) An overview of inflicted head injury in infants and young children, with a review of beta-amyloid precursor protein immunohistochemistry. Arch Pathol Lab Med 130(5):712–7PubMed

25.

Springer JE (2002) Apoptotic cell death following traumatic injury to the central nervous system. J Biochem Mol Biol 35(1):94–105PubMed

26.

Bittigau P, Sifringer M, Felderhoff-Mueser U, Ikonomidou C (2004) Apoptotic neurodegeneration in the context of traumatic injury to the developing brain. Exp Toxicol Pathol 56(1–2):83–9CrossRefPubMed

27.

Newell KL, Boyer P, Gomez-Tortosa E, Hobbs W, Hedley-Whyte ET, Vonsattel JP et al (1999) Alpha-synuclein immunoreactivity is present in axonal swellings in neuroaxonal dystrophy and acute traumatic brain injury. J Neuropathol Exp Neurol 58(12):1263–8CrossRefPubMed

28.

Uryu K, Chen XH, Martinez D, Browne KD, Johnson VE, Graham DI et al (2007) Multiple proteins implicated in neurodegenerative diseases accumulate in axons after brain trauma in humans. Exp Neurol 208(2):185–92CrossRefPubMedPubMedCentral

29.

Kaya SS, Mahmood A, Li Y, Yavuz E, Göksel M, Chopp M (1999) Apoptosis and expression of p53 response proteins and cyclin D1 after cortical impact in rat brain. Brain Res 818(1):23–33CrossRefPubMed

30.

Napieralski JA, Raghupathi R, McIntosh TK (1999) The tumor-suppressor gene, p53, is induced in injured brain regions following experimental traumatic brain injury. Brain Res Mol Brain Res 71(1):78–86CrossRefPubMed

31.

Smith DH, Uryu K, Saatman KE, Trojanowski JQ, McIntosh TK (2003) Protein accumulation in traumatic brain injury. Neuromol Med 4(1–2):59–72CrossRef

32.

Uryu K, Laurer H, McIntosh T, Praticò D, Martinez D, Leight S et al (2002) Repetitive mild brain trauma accelerates Abeta deposition, lipid peroxidation, and cognitive impairment in a transgenic mouse model of Alzheimer amyloidosis. J Neurosci 22(2):446–54CrossRefPubMedPubMedCentral

33.

Chen XH, Johnson VE, Uryu K, Trojanowski JQ, Smith DH (2009) A lack of amyloid beta plaques despite persistent accumulation of amyloid beta in axons of long-term survivors of traumatic brain injury. Brain Pathol 19(2):214–23CrossRefPubMed

34.

Smith C, Graham DI, Murray LS, Nicoll JA (2003) Tau immunohistochemistry in acute brain injury. Neuropathol Appl Neurobiol 29(5):496–502CrossRefPubMed

35.

Geddes JF, Vowles GH, Beer TW, Ellison DW (1997) The diagnosis of diffuse axonal injury: Implications for forensic practice. Neuropathol Appl Neurobiol 23(4):339–47CrossRefPubMed

36.

Geddes JF, Whitwell HL, Graham DI (2000) Traumatic axonal injury: Practical issues for diagnosis in medicolegal cases. Neuropathol Appl Neurobiol 26(2):105–16CrossRefPubMed

37.

Graham DI, Smith C, Reichard R, Leclercq PD, Gentleman SM (2004) Trials and tribulations of using beta-amyloid precursor protein immunohistochemistry to evaluate traumatic brain injury in adults. Forensic Sci Int 146(2–3):89–96CrossRefPubMed

38.

Reichard RR, Smith C, Graham DI (2005) The significance of beta-APP immunoreactivity in forensic practice. Neuropathol Appl Neurobiol 31(3):304–13CrossRefPubMed

39.

Kinney HC (2009) Neuropathology provides new insight in the pathogenesis of the sudden infant death syndrome. Acta Neuropathol 117(3):247–55CrossRefPubMed

40.

Kinney HC (2009) Brainstem mechanisms underlying the sudden infant death syndrome: Evidence from human pathologic studies. Dev Psychobiol 51(3):223–33CrossRefPubMed

41.

Kinney HC, Thach BT (2009) The sudden infant death syndrome. N Engl J Med 361(8):795–805CrossRefPubMedPubMedCentral

42.

Stadelmann C, Lassmann H (2000) Detection of apoptosis in tissue sections. Cell Tissue Res 301(1):19–31CrossRefPubMed

43.

Caffey J (1972) On the theory and practice of shaking infants. Its potential residual effects of permanent brain damage and mental retardation. Am J Dis Child 124(2):161–9CrossRefPubMed

44.

Kempe CH, Silverman FN, Steele BF, Droegemueller W, Silver HK (1962) The battered-child syndrome. JAMA 181:17–24CrossRefPubMed

45.

Matschke J (2008) Historical review of non-accidental head injury in infants and young children. Rechtsmedizin 18(1):7–8CrossRef

46.

Christian CW, Block R (2009) Abusive head trauma in infants and children. Pediatrics 123(5):1409–11

47.

Chiesa A, Duhaime AC (2009) Abusive head trauma. Pediatr Clin N Am 56(2):317–31

48.

Duhaime AC, Christian CW, Rorke LB, Zimmerman RA (1998) Nonaccidental head injury in infants–the "shaken-baby syndrome". N Engl J Med 338(25):1822–9CrossRefPubMed

49.

Adams JH, Doyle D, Ford I, Gennarelli TA, Graham DI, McLellan DR (1989) Diffuse axonal injury in head injury: Definition, diagnosis and grading. Histopathology 15(1):49–59CrossRefPubMed

50.

Lindenberg R, Freytag E (1969) Morphology of brain lesions from blunt trauma in early infancy. Arch Pathol Lab Med 87(3):298–305

51.

Calder IM, Hill I, Scholtz CL (1984) Primary brain trauma in non-accidental injury. J Clin Pathol 37(10):1095–100CrossRefPubMedPubMedCentral

52.

Vowles GH, Scholtz CL, Cameron JM (1987) Diffuse axonal injury in early infancy. J Clin Pathol 40(2):185–9CrossRefPubMedPubMedCentral

53.

Gleckman AM, Bell MD, Evans RJ, Smith TW (1999) Diffuse axonal injury in infants with nonaccidental craniocerebral trauma: Enhanced detection by beta-amyloid precursor protein immunohistochemical staining. Arch Pathol Lab Med 123(2):146–51PubMed

54.

Reichard RR, White CL, Hladik CL, Dolinak D (2003) Beta-amyloid precursor protein staining of nonaccidental central nervous system injury in pediatric autopsies. J Neurotrauma 20(4):347–55CrossRefPubMed

55.

Oehmichen M, Schleiss D, Pedal I, Saternus KS, Gerling I, Meissner C (2008) Shaken baby syndrome: Reexamination of diffuse axonal injury as cause of death. Acta Neuropathol 116(3):317–29CrossRefPubMed

56.

Johnson MW, Stoll L, Rubio A, Troncoso J, Pletnikova O, Fowler DR et al (2011) Axonal injury in young pediatric head trauma: a comparison study of beta-amyloid precursor protein (beta-APP) immunohistochemical staining in traumatic and nontraumatic deaths. J Forensic Sci 56(5):1198–205CrossRefPubMedPubMedCentral

57.

Gentleman SM, Nash MJ, Sweeting CJ, Graham DI, Roberts GW (1993) Beta-amyloid precursor protein (beta APP) as a marker for axonal injury after head injury. Neurosci Lett 160(2):139–44CrossRefPubMed

58.

Büki A, Povlishock JT (2006) All roads lead to disconnection?–Traumatic axonal injury revisited. Acta Neurochir (Wien) 148(2):181–93CrossRef

59.

Yam PS, Takasago T, Dewar D, Graham DI, McCulloch J (1997) Amyloid precursor protein accumulates in white matter at the margin of a focal ischaemic lesion. Brain Res 760(1–2):150–7CrossRefPubMed

60.

Bitsch A, Schuchardt J, Bunkowski S, Kuhlmann T, Brück W (2000) Acute axonal injury in multiple sclerosis. Correlation with demyelination and inflammation. Brain 123(Pt 6):1174–83CrossRefPubMed

61.

Medana IM, Day NP, Hien TT, Mai NT, Bethell D, Phu NH et al (2002) Axonal injury in cerebral malaria. Am J Pathol 160(2):655–66CrossRefPubMedPubMedCentral

62.

Oehmichen M, Meissner C, Schmidt V, Pedal I, König HG (1999) Pontine axonal injury after brain trauma and nontraumatic hypoxic-ischemic brain damage. Int J Legal Med 112(4):261–7CrossRefPubMed

63.

Squier W (2011) The "Shaken Baby" syndrome: Pathology and mechanisms. Acta Neuropathol 122(5):519–42CrossRefPubMed

64.

Squier W, Scheimberg I, Smith C (2011) Spinal nerve root β-APP staining in infants is not a reliable indicator of trauma. Forensic Sci Int 212(1–3):e31–5CrossRefPubMed

65.

Barnes PD, Galaznik J, Gardner H, Shuman M (2010) Infant acute life-threatening event–dysphagic choking versus nonaccidental injury. Semin Pediatr Neurol 17(1):7–11CrossRefPubMed

66.

Richerson GB, Boron WF (2012) Control of ventilation. In: Boron WF, Boulpaep EL (eds) Medical physiology: a cellular and molecular approach. Saunders, Philadelphia, pp 725–46

67.

Smith LH, DeMyer WE (2003) Anatomy of the brainstem. Semin Pediatr Neurol 10(4):235–40CrossRefPubMed

68.

Mellen NM, Thoby-Brisson M (2012) Respiratory circuits: Development, function and models. Curr Opin Neurobiol 22(4):676–85CrossRefPubMed

69.

Matschke J, Laas R (2007) Sudden death due to central alveolar hypoventilation syndrome (Ondine’s curse) in a 39-year-old woman with heterotopia of the inferior olive. Am J Forensic Med Pathol 28(2):141–4CrossRefPubMed

70.

Mendoza M, Latorre JG (2013) Pearls & oy-sters: Reversible Ondine’s curse in a case of lateral medullary infarction. Neurology 80(2):e13–6CrossRefPubMed

71.

Ramirez JM, Richter DW (1996) The neuronal mechanisms of respiratory rhythm generation. Curr Opin Neurobiol 6(6):817–25CrossRefPubMed

72.

Garcia AJ, Zanella S, Koch H, Doi A, Ramirez JM (2011) Networks within networks: the neuronal control of breathing. Prog Brain Res 188:31–50

73.

Smith JC, Abdala AP, Rybak IA, Paton JF (2009) Structural and functional architecture of respiratory networks in the mammalian brainstem. Philos Trans R Soc Lond B Biol Sci 364(1529):2577–87CrossRefPubMedPubMedCentral

74.

Bell E, Shouldice M, Levin AV (2011) Abusive head trauma: a perpetrator confesses. Child Abuse Negl 35(1):74–7CrossRefPubMed

75.

Adamsbaum C, Grabar S, Mejean N, Rey-Salmon C (2010) Abusive head trauma: Judicial admissions highlight violent and repetitive shaking. Pediatrics 126(3):546–55CrossRefPubMed

76.

Biron D, Shelton D (2005) Perpetrator accounts in infant abusive head trauma brought about by a shaking event. Child Abuse Negl 29(12):1347–58CrossRefPubMed

77.

Esernio-Jenssen D, Tai J, Kodsi S (2011) Abusive head trauma in children: a comparison of male and female perpetrators. Pediatrics 127(4):649–57CrossRefPubMed

78.

Hart BL, Dudley MH, Zumwalt RE (1996) Postmortem cranial MRI and autopsy correlation in suspected child abuse. Am J Forensic Med Pathol 17(3):217–24CrossRefPubMed

79.

Brennan LK, Rubin D, Christian CW, Duhaime AC, Mirchandani HG, Rorke-Adams LB (2009) Neck injuries in young pediatric homicide victims. J Neurosurg Pediatr 3(3):232–9CrossRefPubMed

80.

Choudhary AK, Bradford RK, Dias MS, Moore GJ, Boal DKB (2012) Spinal subdural hemorrhage in abusive head trauma: a retrospective study. Radiology 262(1):216–23CrossRefPubMed

81.

Case ME, Graham MA, Handy TC, Jentzen JM, Monteleone JA (2001) Position paper on fatal abusive head injuries in infants and young children. Am J Forensic Med Pathol 22(2):112–22CrossRefPubMed

82.

Case ME (2007) Abusive head injuries in infants and young children. Leg Med (Tokyo) 9(2):83–7CrossRef

Titel: Encephalopathy and death in infants with abusive head trauma is due to hypoxic-ischemic injury following local brain trauma to vital brainstem centers
verfasst von: Jakob Matschke
Andreas Büttner
Markus Bergmann
Christian Hagel
Klaus Püschel
Markus Glatzel
Publikationsdatum: 01.01.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: International Journal of Legal Medicine / Ausgabe 1/2015
Print ISSN: 0937-9827
Elektronische ISSN: 1437-1596
DOI: https://doi.org/10.1007/s00414-014-1060-7

Neu im Fachgebiet Rechtsmedizin

Open Access 15.04.2024 | Biomarker | Schwerpunkt: Next Generation Pathology

Springer Medizin

Encephalopathy and death in infants with abusive head trauma is due to hypoxic-ischemic injury following local brain trauma to vital brainstem centers

Abstract

Background

Methods

Results

Conclusions

Neu im Fachgebiet Rechtsmedizin

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie

Springer Medizin

Abstract

Background

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2015

Splenic hypereosinophilia in anaphylaxis-related death: different assessments depending on different types of allergens?

Utility of amplification enhancers in low copy number DNA analysis

Validation of an immunochromatographic D-dimer test to presumptively identify menstrual fluid in forensic exhibits

Fatal visit to the dentist

Fatal contact shot to the chest caused by the gas jet from a muzzle-loading pistol discharging only black powder and no bullet: case study and experimental simulation of the wounding effect

Forensic age estimation by the Schmeling method: computed tomography analysis of the medial clavicular epiphysis

Neu im Fachgebiet Rechtsmedizin

Molekularpathologische Untersuchungen im Wandel der Zeit

Vergleichende Pathologie in der onkologischen Forschung

Gastrointestinale Stromatumoren

Personalisierte Medizin in der Onkologie