Gray matter injury associated with periventricular leukomalacia in the premature infant

Abstract

Neuroimaging studies indicate reduced volumes of certain gray matter regions in survivors of prematurity with periventricular leukomalacia (PVL). We hypothesized that subacute and/or chronic gray matter lesions are increased in incidence and severity in PVL cases compared to non-PVL cases at autopsy. Forty-one cases of premature infants were divided based on cerebral white matter histology: PVL (n = 17) with cerebral white matter gliosis and focal periventricular necrosis; diffuse white matter gliosis (DWMG) (n = 17) without necrosis; and "Negative" group (n = 7) with no abnormalities. Neuronal loss was found almost exclusively in PVL, with significantly increased incidence and severity in the thalamus (38%), globus pallidus (33%), and cerebellar dentate nucleus (29%) compared to DWMG cases. The incidence of gliosis was significantly increased in PVL compared to DWMG cases in the deep gray nuclei (thalamus/basal ganglia; 50-60% of PVL cases), and basis pontis (100% of PVL cases). Thalamic and basal ganglionic lesions occur almost exclusively in infants with PVL. Gray matter lesions occur in a third or more of PVL cases suggesting that white matter injury generally does not occur in isolation, and that the term "perinatal panencephalopathy" may better describe the scope of the neuropathology.

Fig. 1

Immunoflourescence images of parieto-occipital white matter from a PVL case at 39 postconceptional weeks. O4 labeling (a) is shown in red and GFAP labeling (b) is shown in green. Merged images (c) show no co-localization of O4 and GFAP suggesting two distinct cell populations, i.e. GFAP-positive astrocytes and O4- positive oligodendrocyte precursors, are present. The scale bar represents 50 μm

Fig. 2

Photomicrographs from thalami illustrating neuronal loss scores of 0 (a), 1 (b), 2 (c) and 3 (d). The asterisk in panel b denotes a focal area of neuronal loss. The scale bar represents 20 μm

Fig. 3

Photomicrographs from the inferior olivary nuclei depicting gliosis scores of 0 (a), 1 (b), 2 (c) and 3 (d). Arrows in panels b and c indicate some of the reactive astrocytes that are present. The scale bar represents 20 μm

Fig. 4

GFAP immunohistochemical staining of frontal cortex illustrating non-reactive astrocytes (a) with a linear GFAP-positive process that is perpendicular to glial limitans, which is at the right of this image (not depicted) and a reactive astrocyte (b), with abundant GFAP-positive cytoplasm, and an eccentrically placed, enlarged nucleus. The scale bar represents 20 μm

Fig. 5

Summary diagram comparing gray matter sites with a significantly higher incidence (percentages) of neuronal loss (a) and gliosis (b) in PVL (right of panel) and DWMG (left of panel) cases. Gliosis of the cerebral and cerebellar white matter, basis pontis, brainstem tegmentum and inferior olives is depicted by small red dots, and focal, periventricular necrosis in the cerebral white matter (PVL) is denoted by a large red periventricular circle