Brain damage and axonal injury in a Scottish cohort of neonatal deaths Advance Access publication

in 43% and 27% of the cohort, respectively; max-imally in the subiculum and ventral pons, but often present elsewhere. White matter damage was detected in 24% of cases but without classic cystic lesions of periventricular leucomalacia. b APP positivity was present in neuronal soma in 52% of cases and, in axons, in 27% of cases, and was seen from as early as 25-weeks gestation. Axonal bulbs were clearly delineated by b APP positivity and were usually located in the cerebral white matter and internal capsule, and infrequently in the brain stem. Although white matter damage and b APP axonal positivity were often detected in the same cases ( P = 0.034), these features also occurred independently of each other. Both neuronal karyorrhexes and white matter b APP positivity were significantly correlated with the features of birth asphyxia, particularly a history of seizures. Immunocytochemistry for both b APP and glial fibrillary acidic protein proved useful in detecting neuropathological features which escaped detection on routine examination, particularly in preterm infants. The presence together of recent and older damage in individual brains suggests that there is an ongoing neuronal response to cerebral insults. We find that b APP is a useful marker of white matter damage in the neonatal brain. Immunopositivity for b APP in these circumstances is not attributable to inflicted or accidental trauma. While birth-related trauma cannot be ruled out, hypoxia/ischaemia is a likely cause in these infants. However,theexactpathogenesisofneuronal/axonalinjuryintheneonatalbrainremainsunclear. in neuronal soma and axons were scored as positive or negative for each case. Concordance between the two observers wasachievedin>90%ofcasesanddiscrepantcaseswereresolvedatamultiheadedmicroscopeandbyfurtherreview(J.K.).Thelocaliza-tion and patterns of b APP immunopositivity was correlated with gestation, clinical history and evidence of glial and macrophage reactions, as well as with evidence of neuronal and white matter damage assessed on routine (H&E) staining throughout the brain. Statistical analysis was performed using the x 2 test (Fisher’s exact test where sample size was <20).