Cerebellar hemorrhagic injury in premature infants occurs during a vulnerable developmental period and is associated with wider neuropathology

Abstract

Background

Cerebellar hemorrhagic injury (CHI) is being recognized more frequently in premature infants. However, much of what we know about CHI neuropathology is from autopsy studies that date back to a prior era of neonatal intensive care. To update and expand our knowledge of CHI we reviewed autopsy materials and medical records of all live-born preterm infants (<37 weeks gestation) autopsied at our institution from 1999–2010 who had destructive hemorrhagic injury to cerebellar parenchyma (n = 19) and compared them to matched non-CHI controls (n = 26).

Results

CHI occurred at a mean gestational age of 25 weeks and involved the ventral aspect of the posterior lobe in almost all cases. CHI arose as a large hemorrhage or as multiple smaller hemorrhages in the emerging internal granule cell layer of the developing cortex or in the nearby white matter. Supratentorial germinal matrix hemorrhage occurred in 95% (18/19) of CHI cases compared to 54% (14/26) of control cases (p = 0.003). The cerebellar cortex frequently showed focal neuronal loss and gliosis (both 15/19, 79%) in CHI cases compared to control cases (both 1/26, 4% p < 0.0001). The cerebellar dentate had more neuronal loss (8/15, 53%) and gliosis (9/15, 60%) in CHI cases than controls (both 0/23, 0%; p < 0.0001). The inferior olivary nuclei showed significantly more neuronal loss in CHI (10/17, 59%) than in control cases (5/26, 19%) (p = 0.0077). All other gray matter sites examined showed no significant difference in the incidence of neuronal loss or gliosis between CHI and controls.

Conclusions

We favor the possibility that CHI represents a primary hemorrhage arising due to the effects of impaired autoregulation in a delicate vascular bed. The incidences of neuronal loss and gliosis in the inferior olivary and dentate nuclei, critical cerebellar input and output structures, respectively were higher in CHI compared to control cases and may represent a transsynpatic degenerative process. CHI occurs during a critical developmental period and may render the cerebellum vulnerable to additional deficits if cerebellar growth and neuronal connectivity are not established as expected. Therefore, CHI has the potential to significantly impact neurodevelopmental outcome in survivors.