From physiology to pathology: arousal deficiency theory in sudden infant death syndrome (SIDS)--with reference to apoptosis and neuronal plasticity.
Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died under 6 months of age (including 26 infant victims of sudden infant death syndrome (SIDS), 5 with congenital cardiac abnormalities, 2 from infected pulmonary dysplasia, 2 from septic shock with multi-organ failure, 1 with a prolonged seizure, 1 from prolonged neonatal hypoxemia, 1 from meningitis and brain infarction). The frequency and duration of sleep apneas recorded some 3-12 weeks before the infants' death were analyzed. Brainstem material from these 38 infants was studied in an attempt to elucidate the relationship between sleep apnea and neuronal pathological changes in the arousal pathway. Immunohistochemical analyses included the evaluation of growth-associated phosphoprotein 43 (GAP43) as a marker for synaptic plasticity. The terminal-deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was used to identify apoptosis. The positive pathological reactions were quantitatively analyzed. The pathological and physiological data were linked for each infant. Akaike Information Criterion (AIC) statistics was calculated to elucidate the relationship between the physiological and the pathological data in the SIDS victims. The findings illustrated the possibility of an organic fragility within the arousal pathway, particularly in the midbrain periaqueductal gray matter, which is associated with the "visceral alerting response". This autonomic response occurs within an acetylcholine afferent system and pedunculopontine tegmental nucleus (PPTN). The finding is, in future SIDS infants, associated with repetitive sleep apnea.
D017209:Apoptosis; D017776:Autonomic Pathways / Q000473:pathology; D001933:Brain Stem / Q000473:pathology; D019922:GAP-43 Protein / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D007223:Infant; D009473:Neuronal Plasticity; D017286:Polysomnography; D011446:Prospective Studies; D020181:Sleep Apnea, Obstructive / Q000473:pathology; D020921:Sleep Arousal Disorders / Q000473:pathology*; D013398:Sudden Infant Death / Q000473:pathology*
D019922:GAP-43 Protein