Arcuate nucleus hypoplasia in sudden infant death syndrome: a review

Abnormalities in central ventilatory control during sleep and/or impaired arousal have been reported in some infants who subsequently die of SIDS. Hypothetically, these abnormalities may result from dysfunction of the ventral medullary rim, considered to be an integrative site for cardioventilatory control on the basis of research in animals. This paper summarizes comparative neuroanatomic evidence from a previously published study showing that the human medullary arcuate nucleus is homologous to neurons in the cat which participate in chemosensory/autonomic integrative processes of the ventral medullary rim. Next, it summarizes a study of serially or extensively sectioned medullae of 41 SIDS and 27 controls which identified 2 SIDS victims with isolated hypoplasia of the arcuate nucleus confirmed by three-dimensional reconstructions and volume measurements. The volume of the right arcuate nucleus in the SIDS case was 0.7 mm3, compared to a range of 3.4-26.3 mm3 (median 5 mm3) in 3 infant controls. On the basis of pre-cerebellar and other anatomic connections of the arcuate nucleus and of neurons in homologous positions in animals, arcuate hypoplasia may lead to death by dyssynergy between the cerebellum's influence on cardioventilation and the way this influence is integrated with chemosensation and arousal during sleep and hypercarbia during a critical developmental period.