Medullary arcuate nucleus’ cellular differentiation in SIDS and unexpected late fetal stillbirth cases

Aim of the present study is to analyze the arcuate nucleus (ARCn)’ s cellular component, focusing on the neuronal maturative stage in SIDS victims and stillbirths. The ARCn is an important cardio-respiratory center located in the ventral medullary surface. Some of the present authors have recently detected an ARCn hypoplasia in 30-35% of both SIDS and stillborn cases. This can be unilateral and when is bilateral can involve only a portion of the ARCn. The ARCn’s neuronal density resulted decreased in our SIDS and stillborn cases compared with age-matched controls. Due to the lack of in data on the neuronal maturation, particularly of the ARCn, in the literature, we perform a morphological and morphometric study in a large series of cases (32 cases) between the 17th week of gestation and the first year of age, subdivided into three groups: a) SIDS and stillborn cases with an hypoplastic ARCn (7 cases), b) SIDS and stillborn cases without hypoplastic ARCn (14 cases), c) control cases who died of various different documented causes (11 cases). In every brainstem analyzed on serial sections, the ARCn’s cytoarchitectural and dimensional parameters have been compared with the neurons of the near olivary nucleus, since both the nuclei have the same embryological origin, arising from the basal lamina of the neuronal tube. In the control group (group c), we have found that in fetuses under the 20th week of gestation, both the nuclei have an high density of small undifferentiated neuroblasts of similar size, roundish, apolar, with compact chromatin, nucleolus not clearly identifiable, and scarce cytoplasm. Starting with the 20th week, the olivary nucleus’ cells have bigger size comparing with the ARCn’ s neurons. From the 28th to the 36th week of gestation, the neuroblasts, particularly the ARCn’ s ones, present a polygonal aspect, bipolar, with a big vesicular nucleus with loose chromatin. In the olivary nucleus the cells have a similar aspect, but are more roundish. After the birth, the neurons, often multipolar, are diminished in number. The nucleus is roundish with finely scattered chromatin and the nucleolus is much more evident comparing with the prenatal period. The same differentiation neuronal model resulted from the observation of the brainstem of subjects dying suddenly and unexpectedly. In the 20% of SIDS cases with a normal ARCn’ s architecture (group b), an increase of the neuronal density has been observed, predominantly with lengthened neurons, with flattened nucleus, compact chromatin and poorly evident nucleolus. Thus, in some infants dying of SIDS a normally developed ARCn, could present an anomalous neuronal maturation. This maturation defect could be the morphological substrate for a deficit in a specific neurotransmitter responsible for a subsequent alteration of the ARCn’ s chemoreceptorial function.