Brain Advance Access originally published online on February 10, 2005
Brain 2005 128(5):1070-1081; doi:10.1093/brain/awh436
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Brain damage and axonal injury in a Scottish cohort of neonatal deaths
1 Division of Pathology and 2 Division of Child Life and Health, University of Edinburgh, Edinburgh, UK
Correspondence to: Jeanne Bell BSc MD FRCPath FRSE, Professor of Neuropathology, Division of Pathology (Neuropathology), Alexander Donald Building, Western General Hospital, Edinburgh EH4 2XU, UK E-mail: Jeanne.Bell{at}ed.ac.uk
Despite the clinical and medicolegal significance attached to perinatal asphyxia, the neuropathological basis of this condition remains obscure. There are very few studies in the literature which correlate the pathological findings in neonatal brains with detailed epidemiological data, and none which are population based. In a Scotland-wide study of neonatal deaths, 70 brains have been examined. On the basis of glial and macrophage reactions, we previously identified infants with putative antepartum brain damage in this cohort and have related these reactions to signs of birth asphyxia. The present study explores the extent of neuronal/axonal injury in these infants since this is likely to be the basis for neurological deficits in surviving infants. We have also investigated these brains for ß-amyloid precursor protein (ßAPP) positivity to determine whether this is a useful marker of neuronal injury in neonates. Neuronal eosinophilia and karyorrhexes were detected in 43% and 27% of the cohort, respectively; maximally 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. ßAPP 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 ßAPP positivity and were usually located in the cerebral white matter and internal capsule, and infrequently in the brain stem. Although white matter damage and ßAPP 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 ßAPP positivity were significantly correlated with the features of birth asphyxia, particularly a history of seizures. Immunocytochemistry for both ßAPP 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 ßAPP is a useful marker of white matter damage in the neonatal brain. Immunopositivity for ßAPP 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, the exact pathogenesis of neuronal/axonal injury in the neonatal brain remains unclear.
With the collaboration of the Scottish paediatric pathologists and neuropathologists Drs N. Alsanjari, D. Doyle, I. Graham, E. Gray, A. G. Howatson, S. Lang, A. M. Lutfy, J. McCullough, J. MacKenzie, K. J. McKenzie, J. McPhie, R. Nairn and N. Smith
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