Delayed Central Nervous System Myelination in the Sudden Infant Death Syndrome

Abstract

This study was designed to assess whether development of the central nervous system (CNS) is delayed in victims of the sudden infant death syndrome (SIDS). We selected the parameter of myelination because it is a continuously changing and readily accessible marker of CNS development in the SIDS age-range. We assessed myelination blindly in 61 SIDS and 89 autopsy controls. In 62 sites the degree of myelination was visually graded in myelin-stained histological sections on an ordinal scale of 0-4 using the inferior cerebellar peduncle as an internal standard of degree 3. Cases were stratified by postconceptional age at death and SIDS and controls were compared with respect to myelin degree at each site. Significantly delayed myelination (p less than 0.05) occurred in the SIDS group in 25 of the 62 sites examined. Hypomyelination affected fiber systems in which myelination is initiated before or after birth and which myelinate with different tempos and preferentially affect pyramidal and cerebellar (somatomotor) and prefrontal-temporal-limbic (visceromotor) systems. Hypomyelination was not associated with individual clinicopathologic variables in the SIDS group. Somatic growth and brain weight were significantly greater in SIDS than controls. Therefore, we suggest that SIDS is associated with a developmental CNS disorder. Although delayed CNS myelination most likely shares a common antecedent with sudden death and is not its cause, the role of somato- and viscero-motor systems in central cardiorespiratory control and arousal warrants further analysis in SIDS.

Neuropathology provides new insight in the pathogenesis of the sudden infant death syndrome

“…The reports in SIDS cases of subtle, albeit non-speciWc, gliosis in the brainstem is of particular interest, as this structure is a recognized region of vulnerability to hypoxiaischemia in early life, particularly the inferior olive [54]. In addition, apoptosis has been reported in brainstem nuclei of SIDS cases, consistent with hypoxia-induced programmed cell death [74] Importantly, histopathologic abnormalities consistent with hypoxia-ischemia have also been reported in regions rostral to the brainstem, including reactive microglia in the hippocampus [9], increased number of copper/zinc superoxide dismutase-and glutathione peroxidaseexpressing neurons in the hippocampus [19], cerebral white matter gliosis [26], and periventricular leukomalacia [26,70]. While forebrain and brainstem abnormalities have yet to be reported in the same SIDS cases in a single study, the topography and cellular features in combination are consistent with hypoxic-ischemic injury in susceptible regions in the human infant brain, i.e., brainstem, hippocampus, and cerebral white matter.…”

“…Thus, a primary defect in this site may impair protective responses to hypercapnia generated by rebreathing exhaled gases in the face-down position or upper airway occlusion. Other brain Wndings suggest the possibility that acquired hypoxic-ischemic injury also occurs in SIDS cases during the fetal period, i.e., periventricular leukomalacia [26,70], a recognized lesion of vulnerable fetal white matter, with a peak at 28-34 gestational weeks, and neuronal necrosis and apoptosis in the arcuate nucleus in unexplained stillbirth, potentially leading to underpopulation of arcuate neurons mimicking hypoplasia [15]. In addition, placental abnormalities with features of maternal vascular underperfusion that can lead to fetal hypoxia have been linked to SIDS [16].…”

Unexplained stillbirth versus SIDS: Common congenital diseases of the autonomic nervous system—pathology and nosology

“…Subcortical leukomalacia in the white matter [22], developmental delay of dendritic spines and synapses [23], a decreased number of myelinated vagal fibers [24], increased apoptosis in brainstem nuclei [25] and abnormalities in neurotransmitters [26] have all been reported in the SIDS in subsequent research.…”

Estimation of Mean Nuclear Volume of Neocortical Neurons in Sudden Infant Death Syndrome Cases Using the Nucleator Estimator Technique

“…A detailed literature review of a developmental neurological perspective on SIDS is presented by O'Brien [3]. Neuropathological findings specific to delayed myelination in areas of the brain where myelination is initiated before or after birth have been reported in SIDS victims [4][5][6]. The cause(s) of this delay is unknown, but multiple toxic, hormonal, nutritional and genetic factors are known to adversely affect myelin formation in humans and in animals [7][8][9].…”