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

TY - JOUR

T1 - Encephalopathy and death in infants with abusive head trauma is due to hypoxic-ischemic injury following local brain trauma to vital brainstem centers

AU - Matschke, Jakob

AU - Büttner, Andreas

AU - Bergmann, Markus

AU - Hagel, Christian

AU - Püschel, Klaus

AU - Glatzel, Markus

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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.

AB - 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.

U2 - 10.1007/s00414-014-1060-7

DO - 10.1007/s00414-014-1060-7

M3 - SCORING: Journal article

C2 - 25107298

VL - 129

SP - 105

EP - 114

JO - INT J LEGAL MED

JF - INT J LEGAL MED

SN - 0937-9827

IS - 1

ER -