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Subtle quantitative abnormalities in neuronal populations derived from the rhombic lip (i.e. arcuate nucleus at the ventral medullary surface, external granular layer of the cerebellum) have been reported in victims of the sudden infant death syndrome (SIDS). In this study, we examined the inferior olive, a major rhombic lip derivative, to determine if subtle rhombic lip abnormalities also involve this nucleus in SIDS. We analyzed the number and density of neurons and reactive astrocytes in the inferior olive in 29 SIDS cases and 29 controls. Computer-assisted cell counting procedures were used in sections stained with hematoxylin and eosin/Luxol fast blue. There was a significant difference in the postconceptionally age-adjusted mean for neuronal density between SIDS cases (7,687 +/- 255 neurons/mm(3)) and controls (8,889 +/- 255 neurons/mm(3)) (p = 0.002). The difference in age-adjusted mean neuronal number between SIDS cases (1,932 +/- 89 neurons/2 sections) and controls (2,172 +/- 89 neurons/2 sections) was marginally significant (p = 0.063). Reactive astrocytes were present in the inferior olive in SIDS cases, but their number, density, and developmental profile were not significantly different from that of control infants dying of diverse known causes. SIDS victims found dead in cribs, beds, and sofas, prone or supine had subtle olivary abnormalities, suggesting that affected infants are at risk in various sleeping situations. We propose that at least some SIDS victims experience intrauterine brainstem injury including the olivo-arcuato-cerebellar circuitry derived from the rhombic lip. These observations provide future directions for SIDS research concerning the role of early insults in pregnancy, the rhombic lip, and the interactions of the ventral medulla and cerebellum in cardioventilatory control.

Subtle Developmental Abnormalities in the Inferior Olive: An Indicator of Prenatal Brainstem Injury in the Sudden Infant Death Syndrome