Encephalopathy and death in infants with abusive head trauma is due to hypoxic-ischemic injury following local brain trauma to vital brainstem centers
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).
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.
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).
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.
KeywordsAbusive head trauma Non-accidental head injury Shaken baby syndrome Child abuse Diffuse axonal injury Neuropathology
Mrs Monika Thiel for excellent artwork in Fig. 2. Ms Sandra Deutsch and Ms Kendra Richter for excellent histology and immunohistochemical work.
As indicated earlier, all studies were in accordance with ethical standards and regulations at the University Medical Center Hamburg-Eppendorf; furthermore, this study was approved by the official ethical institutional review board of the Hamburg medical association (WF 042/12).
Conflict of interest
The authors declare no conflicts of interest
- 1.Keenan HT (2010) Epidemiology of abusive head trauma. In: Jenny C (ed) Child abuse and neglect: diagnosis, treatment and evidence. Saunders, p. 35–39Google Scholar
- 11.Leestma JE (2009) Forensic neuropathology. CRC Press Taylor & Francis Group, Boca RatonGoogle Scholar
- 14.Oehmichen M, Auer RN, König HG, Jellinger KA (2006) Forensic neuropathology and associated neurology. Springer, Berlin, 660 pGoogle Scholar
- 15.Itabashi HH, Andrews JM, Tomiyasu U (2007) Forensic neuropathology: a practical review of the fundamentals. Elsevier, 481 pGoogle Scholar
- 46.Christian CW, Block R (2009) Abusive head trauma in infants and children. Pediatrics 123(5):1409–11Google Scholar
- 47.Chiesa A, Duhaime AC (2009) Abusive head trauma. Pediatr Clin N Am 56(2):317–31Google Scholar
- 50.Lindenberg R, Freytag E (1969) Morphology of brain lesions from blunt trauma in early infancy. Arch Pathol Lab Med 87(3):298–305Google Scholar
- 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):1198–205PubMedCentralPubMedCrossRefGoogle Scholar
- 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 725–46Google Scholar
- 72.Garcia AJ, Zanella S, Koch H, Doi A, Ramirez JM (2011) Networks within networks: the neuronal control of breathing. Prog Brain Res 188:31–50Google Scholar