Arcuate nucleus hypoplasia in the sudden infant death syndrome

Abnormalities in central respiratory control during sleep, arousal and/or cardiac activity have been reported in some infants who subsequently die of the sudden infant death syndrome (SIDS). We postulate that these abnormalities may result from dysfunction of the ventral and ventrolateral medulla, which, based on animal data, is an integrative site for chemosensitivity, ventilation, autonomic function, and arousal. The arcuate nucleus along the ventral surface of the human medulla has been proposed to facilitate chemosensitivity to carbon dioxide and/or hydrogen ion. In this study, we surveyed serially or extensively sectioned medullae of 41 SIDS and 27 controls, and identified two SIDS victims with isolated hypoplasia of the arcuate nucleus. Three-dimensional reconstructions and volume measurements of each hemimedulla of one of these SIDS victims and three controls were performed from serial sections. The volume of the right arcuate nucleus of the SIDS case was 0.7 mm3, compared to a range of 3.4-26.3 mm3 (median 5 mm3) in three infant controls. On the basis of the anatomic connections of the human arcuate nucleus and of neurons in homologous positions in animals, we postulate that arcuate hypoplasia may lead to death by dyssynergy between cerebellar coordination of ventilation and autonomic/chemosensory/arousal integration, especially during sleep, hypercarbia, and in a critical developmental period.