title: 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
  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.
authors.affiliation: Forensic Neuropathology Unit, University Medical Centre Hamburg-Eppendorf, 20246, Hamburg, Germany, matschke@uke.de.
authors.forename: Jakob
authors.initials: J
authors.lastname: Matschke
authors.forename: Andreas
authors.initials: A
authors.lastname: Büttner
authors.forename: Markus
authors.initials: M
authors.lastname: Bergmann
authors.forename: Christian
authors.initials: C
authors.lastname: Hagel
authors.forename: Klaus
authors.initials: K
authors.lastname: Püschel
authors.forename: Markus
authors.initials: M
authors.lastname: Glatzel
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000150:complications*; D001933:Brain Stem / Q000378:metabolism; D016022:Case-Control Studies; D063226:Central Pattern Generators / Q000293:injuries*; D002649:Child Abuse; D020833:Diffuse Axonal Injury / Q000473:pathology; D005130:Eye Hemorrhage / Q000473:pathology; D005260:Female; D049429:Forensic Pathology; D006408:Hematoma, Subdural / Q000473:pathology; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology / Q000473:pathology*; D007150:Immunohistochemistry; D007223:Infant; D007231:Infant, Newborn; D008297:Male
chemical_list: D016564:Amyloid beta-Protein Precursor
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