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Abnormalities of the dorsal motor nucleus of the vagus in sudden infant death syndrome

Recent hypotheses concerning the pathogenesis of sudden infant death syndrome (SIDS) have focused on developmental abnormalities of the central nervous system, which are believed to produce cardiorespiratory instability in susceptible infants. The present study was designed to investigate developmental abnormalities in the dorsal motor nucleus of the vagus (DMV) in SIDS. Using serial histological sections of the brainstem from SIDS cases and agematched control cases without neurological disease, morphometric analyzes were performed to compare postnatal changes in 1) the total volume of the DMV, 2) the numerical density of neurons (N v , cells per mm 3), 3) the total number of neurons, and 4) mean neuronal profile area. In the SIDS cases there was a significant increase in the total volume of the DMV (33%), when compared to controls. In SIDS there was a significant decrease in the N v of neurons (33%), although the total number of neurons did not differ significantly from controls. Mean neuronal profile areas were significantly greater in SIDS for both motor (31 &) and non-motor (30%) neurons, when compared to controls. These changes are consistent with an overgrowth of the DMV during early postnatal development. Given the role of the DMV in the autonomic control of breathing and heart rate, this subtle developmental disorder likely contributes to the cardiorespiratory instability characteristic of susceptible infants. Given the possibility that increased expression of insulin-like growth factor I during early postnatal development might contribute to this overgrowth, morphometric analyses were performed on the DMV and hypoglossal nucleus (HN) in transgenic mice, which overexpress IGF-I postnatally, and in normal littermate controls on postnatal day 35. Morphometric variables included 1) the total volumes of the DMV and HN, 2) the N v of neurons, 3) the total number of neurons, and 4) the mean neuronal profile areas. In transgenic mice there was a significant increase in the volumes of both the DMV (84%) and the HN (30%). The N v of neurons was significantly reduced in both nuclei in transgenic mice. In the DMV, however, there was a significant increase in the total number of neurons (56%). In the HN, the total