Investigation into the correlation in SIDS victims between Alzheimer precursor protein A4 in the brainstem and sleep apnea.

BACKGROUND: Recently, the appearance of beta-amyloid precursor protein (APP) has been demonstrated in the neonatal brain following hypoxic-ischaemic injury. As chronic hypoxia is one of the favoured theories of causation in the sudden infant death syndrome (SIDS), the correlation between APP in the brainstem and sleep apnea in SIDS was investigated. MATERIALS AND METHODS: Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died under 6 months of age, which included 26 cases of SIDS. All the infants had been recorded during one night in a pediatric sleep laboratory, some 3 to 12 weeks before death. The frequency and duration of sleep apnea were analyzed. The brainstem material was collected and immunohistochemistry with anti-Alzheimer precursor protein A4 (APP) was carried out. The density of APP-positive elements was measured semi-quantitatively. Correlation analyses were carried out between the density of APP-positive elements and the data on sleep apnea. RESULTS: No correlation was found. CONCLUSION: No correlation between pathological data of APP and physiological data of sleep apnea was not in agreement with the association of sleep apnea in pathophysiology of SIDS.

Analysis of STR polymorphisms in the northeast Chinese population.

The distribution of allele frequencies for 12 short tandem repeats (STR) loci were determined in 300 unrelated healthy Chinese individuals living in northeast of China, using AmpFlSTR Profiler Plus kit and AmpFlSTR Green I kit (PE, Applied Biosystems). In these samples, 123 alleles and 399 genotypes were observed for 12 STR loci. The distribution of these observed genotypes were not significantly different from the expected distribution according to Hardy-Weinberg equilibrium.

From epidemiology to physiology and pathology: apnea and arousal deficient theories in sudden infant death syndrome (SIDS)--with particular reference to hypoxic brainstem gliosis.

Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died under 6 months of age. They included 26 cases of sudden infant death syndrome (SIDS). Five infants who died from congenital cardiac abnormalities, two from infected pulmonary dysplasia, two from septic shock with multi-organ failure, one during a prolonged seizure, one from a prolonged neonatal hypoxemia, one from meningitis with brain infarction. All the infants had been recorded during one night in a pediatric sleep laboratory some 3-12 weeks before death. The frequency and duration of sleep apneas were analyzed. The infants' brain stem material was collected and immunohistochemistry of glial fibrillary acidic protein (GFAP) was carried out. The density of GFAP-positive reactive astrocytes was measured in the cardiorespiratory and arousal pathway. Akaike information criterion statistics (AIC) were calculated to elucidate the relationship between the epidemiological data on sleep position, the physiological data and the pathological data in SIDS victims. The duration of obstructive apnea was the most significant variable to differentiate between SIDS victims and control infants. In conclusion, the present study sustains the possibility of an organic fragility within the arousal pathway in SIDS victims with repetitive sleep apneas.

Association between sleep apnea and reactive astrocytes in brainstems of victims of SIDS and in control infants.

Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died under 6 months of age; 27 infants died from sudden infant death syndrome (SIDS), 5 from congenital cardiac abnormalities, 2 from infected pulmonary dysplasia, 2 from septic shock with multi-organ failure, 1 with a prolonged seizure, and another with prolonged neonatal hypoxemia. The frequency and duration of sleep apneas recorded some 3-12 weeks prior to the infants' death were analyzed. Brainstem material was retrospectively collected from these 33 infants and studied in an attempt to elucidate the relationship between sleep apnea and hypoxic gliosis. The findings were compared between the SIDS victims and the control infants. Brainstem materials were immunohistochemically studied for quantitization of reactive astrocytes using an anti-glial fibrillary acidic protein (GFAP) antibody. The pathological materials were collected within 24h of death. This study focuses on the association between respiratory characteristics and pathology. Physiological and pathological data in the arousal pathway of the brainstem were linked for each infant and variant-covariant analyses were carried out using physiological data as dependent variables and pathological data and categorical data to evaluate the association with SIDS or non-SIDS as independent variables. The study failed to statistically support an association between hypoxic loads, reflected by the GFAP-positive reactive astrocytes in brainstems, the classification of being SIDS or non-SIDS infants, and the characteristics of sleep apnea.

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.

Interaction between apnea, prone sleep position and gliosis in the brainstems of victims of SIDS.

Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died suddenly and unexpectedly under 6 months of age. Of these, 26 died from sudden infant death syndrome (SIDS), 5 from congenital cardiac abnormalities, 2 from infected pulmonary dysplasia, 2 from septic shock with multi-organ failure, 1 from a prolonged seizure, 1 from prolonged neonatal hypoxemia, and 1 from meningitis and brain infarction. The frequency and duration of apneas recorded some 3-12 weeks prior to the infants' death were analyzed. The brainstem materials were collected and studied in an attempt to elucidate the relationship between sleep apnea, and prone sleep position and gliosis in some nuclei associated with cardiorespiratory characteristics, such as nucleus ambiguus in the medulla oblongata and the solitary nucleus, as well as structures associated with arousal phenomenon, such as the reticular formation, the superior central nucleus and the nucleus raphe magnus in the pons, the dorsal raphe nuclei in the midbrain and medulla oblongata, periaqueductal gray matter in midbrain, and locus ceruleus. Gliosis was estimated as the density of glial fibrillary acidic protein (GFAP)-positive reactive astrocytes. Variant-covariant analyses were carried out using the characteristics of apnea as an independent variable and sleep position and gliosis as dependent variables. A significant association was found only in the frequency of obstructive apnea and prone position (P<0.001) and gliosis in the raphe nuclei in the midbrain (P<0.001). Although prone position is a well-known risk factor for SIDS, the frequency of obstructive apnea has not been associated with the prone sleep position. The observed relation between prone sleep and the density of gliosis does not relate to epidemiological findings. Further studies are needed to investigate the unexpected statistical association.

Arousal deficiency theory in sudden infant death syndrome with reference to neuronal plasticity.

OBJECTIVE: 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), five with congenital cardiac abnormalities, two from infected pulmonary dysplasia, two from septic shock with multi-organ failure, one with a prolonged seizure, one from prolonged neonatal hypoxemia and one from meningitis and brain infarction). METHOD: The frequency and duration of sleep apnea events recorded some 3-12 weeks before the infants' deaths 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. The histochemical analyses included Bielschowsky staining and the immunohistochemical analyses included the evaluation of growth-associated phosphoprotein 43 (GAP43) and of synaptophysin as markers for synaptic plasticity. Neurofibrae with positive pathological reactions were quantitatively analyzed. Pathological and physiological data were linked for each infant. RESULTS: The correlation between sleep apnea and neuronal plasticity in the arousal pathway of the SIDS victims was not seen in the control infants and the correlation between sleep apnea and neuronal plasticity in the arousal pathway found in the control infants was not seen in the SIDS victims. CONCLUSION: These findings suggest that neuronal plasticity in the brainstem arousal pathway is related with SIDS.