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Annink KV, Meerts L, van der Aa NE, Alderliesten T, Nikkels PGJ, Nijboer CHA, Groenendaal F, de Vries LS, Benders MJNL, Hoebeek FE, Dudink J. Cerebellar injury in term neonates with hypoxic-ischemic encephalopathy is underestimated. Pediatr Res. 2020 Sep 23. doi: 10.1038/s41390-020-01173-z. Epub ahead of print. PMID: 32967002.

Background: Postmortem examinations frequently show cerebellar injury in infants with severe hypoxic-ischemic encephalopathy (HIE), while it is less well visible on MRI. The primary aim was to investigate the correlation between cerebellar apparent diffusion coefficient (ADC) values and histopathology in infants with HIE. The secondary aim was to compare ADC values in the cerebellum of infants with HIE and infants without brain injury.

Methods: ADC values in the cerebellar vermis, hemispheres and dentate nucleus (DN) of (near-)term infants with HIE (n = 33) within the first week after birth were compared with neonates with congenital non-cardiac anomalies, normal postoperative MRIs and normal outcome (n = 22). Microglia/macrophage activation was assessed using CD68 and/or HLA-DR staining and Purkinje cell (PC) injury using H&E-stained slices. The correlation between ADC values and the histopathological measures was analyzed.

Results: ADC values in the vermis (p = 0.021) and DN (p < 0.001) were significantly lower in infants with HIE compared to controls. ADC values in the cerebellar hemispheres were comparable. ADC values in the vermis were correlated with the number and percentage of normal PCs; otherwise ADC values and histology were not correlated.

Conclusion: Histopathological injury in the cerebellum is common in infants with HIE. ADC values underestimate histopathological injury.

Impact: ADC values might underestimate cerebellar injury in neonates with HIE.ADC values in the vermis and dentate nucleus of infants with HIE are lower compared to controls, but not in the cerebellar hemispheres.Abnormal ADC values are only found when cytotoxic edema is very severe.ADC values in the vermis are correlated with Purkinje cell injury in the vermis; furthermore, there were no correlations between ADC values and histopathological measures.

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