BCL11A frameshift mutation associated with dyspraxia and hypotonia affecting the fine, gross, oral, and speech motor systems.

We report the case of a 7-year-old male of Western European origin presenting with moderate intellectual disability, severe childhood apraxia of speech in the presence of oral and manual dyspraxia, and hypotonia across motor systems including the oral and speech motor systems. Exome sequencing revealed a de novo frameshift protein truncating mutation in the fourth exon of BCL11A, a gene recently demonstrated as being involved in cognition and language development. Making parallels with a previously described patient with a 200 kb 2p15p16.1 deletion encompassing the entire BCL11A gene and displaying a similar phenotype, we characterize in depth how BCL11A is involved in clinical aspects of language development and oral praxis.

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.

Clinicopathological correlation between brainstem gliosis using GFAP as a marker and sleep apnea in the sudden infant death syndrome.

BACKGROUND: Chronic hypoxia, leading to brainstem gliosis, has been postulated as a factor in the sudden infant death syndrome (SIDS), which is still the main cause of postneonatal infant death. Gliosis detected by immunohistochemistry of glial fibrillary acidic protein (GFAP) is a marker of apoptosis. The correlation between GFAP-positive reactive astrocytes 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, including 26 cases of SIDS. The frequency and duration of sleep apnea were analyzed. Brainstem material was collected and immunohistochemistry of GFAP carried out. The density of GFAP-positive reactive astrocytes was measured quantitatively. Correlation analyses were carried out between the data on gliosis and the physiological data of sleep apnea. RESULTS: A SIDS-specific negative correlation between the density of gliosis in the dorsal vagus nucleus in the medulla oblongata and the frequency of obstructive apnea (p=0.022) was found. CONCLUSIONS: A significant SIDS-specific correlation with gliosis in the dorsal vagus nucleus and the characteristics of sleep apnea might invite the cardiorespiratory changes in SIDS.

Pathological data on apoptosis in the brainstem and physiological data on sleep apnea in SIDS victims.

UNLABELLED: The sudden infant death syndrome (SIDS) is still the main cause of postneonatal infant death and its cause is still unknown. A chronic hypoxic situation has been shown to exist in the brains of SIDS victims and apoptosis has been demonstrated in hypoxic situations. In this study, the correlation between apoptotic neurons or glias and sleep apnea in SIDS was investigated in the brainstem of SIDS victims. MATERIALS AND METHODS: In a cohort of 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died under 6 months of age. They included 26 cases of SIDS. The frequency and duration of sleep apnea were analyzed. The brainstem material was collected and terminal-deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method was carried out. The density of TUNEL-positive neurons or glias was measured quantitatively. Correlation analyses were carried out between the apoptosis-associated pathological data and the physiological data of sleep apnea. RESULTS: No significant negative or positive correlation between the density of TUNEL-positive neurons or glias and the characteristics of sleep apnea was observed in SIDS victims. No statistically significant differences associated with apoptotic neurons and glias were observed between SIDS and non-SIDS. CONCLUSIONS: The pathological findings of apoptosis were not in agreement with the hypothesis refer to apnea and arousal phenomenon in pathophysiology of SIDS.

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.

The correlation between serotonergic neurons in the brainstem and sleep apnea in SIDS victims.

BACKGROUND: In the Sudden Infant Death Syndrome (SIDS), a medullary serotonergic network deficiency theory has been proposed, amongst many other hypotheses. The correlation between serotonergic neurons or dendritic spines in the brainstem of SIDS and sleep apnea was investigated here. MATERIALS AND METHODS: Twenty-seven thousand infants were studied prospectively to characterize their sleep-wake behavior. Of these, 38 infants died under 6 months of age, including 26 cases of SIDS. The frequency and duration of sleep apnea were analyzed. Brainstem material was collected and immunohistochemistry for tryptophan hydroxylase (TrypH) carried out. The density of TrypH-positive neurons was measured quantitatively. Correlation analyses were carried out between the TrypH-associated pathological data and the physiological data of sleep apnea. RESULTS: One significant positive correlation between the density of TrypH-positive neurons in the dorsal raphe nucleus of the midbrain and the duration of central apnea (p=0.027) was found in SIDS victims. CONCLUSIONS: Some of serotonergic facts could be involved in the pathophysiology of SIDS.

The correlation between ubiquitin in the brainstem and sleep apnea in SIDS victims.

BACKGROUND: The sudden infant death syndrome (SIDS) is still the main cause of postneonatal infant death and its etiology has stimulated many competing theories, among which is the role of hypoxia and brainstem abnormalities. One report claims an increased in ubiquitin in the liver of SIDS victims, ubiquitin being one of the heat-shock proteins. The correlation between ubiquitin in the brainstem and sleep apnea in SIDS was investigated here. MATERIALS AND METHODS: Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died under 6 months of age, including 26 cases of SIDS. 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 apnea were analyzed. Brainstem material was collected at autopsy and examined immunohistochemically for ubiquitin. The density of ubiquitin-positive elements was measured semiquantitatively. Correlation analyses were carried out between the density of ubiquitin-positive elements and the data on sleep apnea. RESULTS: In the victims of SIDS, a statistically significant positive correlation was found between the density of ubiquitin-positive neuronal factors in the pons and the frequency of obstructive apnea (p=0.001) and statistically significant negative correlations were seen between the density of ubiquitin-positive cells in the ependyma in the pons and the duration of obstructive apnea (p=0.044) and between the density of ubiquitin-positive cells in the subependyma in the medulla and the frequency of central apnea (p=0.024). CONCLUSIONS: It was found that three significant associations existed between the pathological data referring to ubiquitin and physiological data in SIDS victims. These facts are in agreements with the association of sleep apnea in SIDS.

The correlation between microtubule-associated protein 2 in the brainstem of SIDS victims and physiological data on sleep apnea.

BACKGROUND: Microtubule-associated protein 2(MAP2), a cytoskeletal protein of the neuron, is a marker of early ischemic neuronal damage. As a chronic hypoxic situation exists in the brains of victims of the sudden infant death syndrome (SIDS), the correlation between MAP2-positive neurons or dendritic spines in the brainstem and sleep apnea was investigated in SIDS, which is still the main cause of postneonatal infant death. MATERIALS AND METHODS: 27,000 infants were studied prospectively to characterize their sleep-wake behavior and amongst these, 38 infants died under 6 months of age. They included 26 cases of SIDS. The frequency and duration of sleep apneae were analyzed. The brainstem material was collected and immunohistochemistry of MAP2 was carried out. The density of MAP2-positive neurons, dendrites and dendritic spines were measured quantitatively. Correlation analyses were carried out between the MAP2-associated pathological data and the physiological data of sleep apnea. RESULTS: One negative correlation between the density of MAP2-positive dendrites in the pars compacta of pedunculo-pontine tegmentum nucleus (PPTNc) and the duration of obstructive apnea (p=0.017) and two SIDS-specific positive correlations between the density of MAP2-positive dendrites in the pars dissipata of pedunculo-pontine tegmentum nucleus (PPTNd) and the duration of central apnea (p=0.005) and between the dorsal raphe and the frequency of obstructive apnea were found in SIDS victims. The density of MAP2-positive dendritic spines in PPTNc was significantly higher in SIDS than in control (p=0.034). CONCLUSIONS: The significant correlations with the MAP2-positive findings in the midbrain arousal pathway and the characteristics of sleep apnea in SIDS victims were in agreement with the association with apnea and arousal-deficiency in SIDS.

The correlation between tau protein in the brainstem and sleep apnea in SIDS victims.

BACKGROUND: Recently, it has been reported that neuronal plasticity in the brainstem arousal pathway is related to the sudden infant death syndrome (SIDS). Tau protein may contribute to axonal development and neural plasticity; therefore, the correlation between tau protein in the brainstem and sleep apnea in SIDS was investigated here. MATERIALS AND METHODS: Among 27,000 infants studied prospectively to characterize their sleep-wake behavior, 38 infants died under 6 months of age, including 26 cases of SIDS. The frequency and duration of sleep apnea were analyzed on all the infants, having been recorded during one night in a pediatric sleep laboratory some 3-12 weeks before death. The brainstem material was collected and immunohistochemistry of tau was carried out. The density of tau-positive elements was measured semiquantitatively. Correlation analyses were carried out between the density of tau-positive elements and the data of sleep apnea. RESULTS: In the 26 SIDS cases, tau-positive findings were observed in the sub-pia mater in two cases, in the colloid plexus in one case, in the ependyma and subependyma in five cases, in neurons in two cases and as a general diffusion in one case. In 12 control cases, tau-positive findings were observed in the sub-pia mater in one case and in neuronal elements in three cases. No correlation was found on analysis. CONCLUSIONS: There was no correlation between the finding of tau in the brainstem of SIDS victims and the incidence of sleep apnea.

The presence of TATA-binding protein in the brainstem, correlated with sleep apnea in SIDS victims.

BACKGROUND: Recent reports have indicated that the presence of transcription factors and RNA polymerase decreases in rat brains that suffer perinatal asphyxia from hypoxia. As hypoxia has been proposed as a causative factor in the Sudden Infant Death Syndrome (SIDS), the correlation between TATA-binding protein (TBP) in the brainstem of SIDS victims as a marker of transcription and the incidence of sleep apnea was investigated. MATERIALS AND METHODS: A total of 38 infants, including 26 cases of SIDS, died under 6 months of age, in a cohort of 27,000 infants studied prospectively to characterize their sleep-wake behavior. The frequency and duration of sleep apnea was analyzed. Brainstem material was collected and immunohistochemistry of TBP was carried out. The density of TBP-positive neurons was measured quantitatively. Correlation analyses were carried out between the density of TBP-positive neurons and the data concerning sleep apnea. RESULTS: One SIDS-specific positive correlation occurred between the density of TBP-positive neurons in the dorsal raphe nucleus of the midbrain and the duration of central apnea (p=0.049) and two SIDS-specific negative correlations between the density of TBP-positive neurons in the pars compacta and dissipata of the pedunculopontine tegmentum nucleus (PPTNc, PPTNd) in the midbrain and the duration of apnea (p=0.035). CONCLUSIONS: The significant correlation between the findings of TBP-positive neurons in the midbrain arousal pathway and the characteristics of sleep apnea in SIDS victims is in agreement with the both association of apnea and arousal phenomenon in pathophysiology of SIDS.

Correlation between the Ki-67 antigen in the brainstem and physiological data on sleep apnea in SIDS victims.

BACKGROUND: The Ki-67 antigen appears in all human proliferating cells during late G1, S, M and G2 phases of the cell cycle, but is consistently absent in the Go phase (noncycling) cells. The correlation between Ki-67 in the brainstem and sleep apnea in victims of the sudden infant death syndrome (SIDS) was investigated to elucidate cell kinetics in the brainstem of this condition, which is still the main cause of postneonatal infant death. MATERIALS AND METHODS: Twenty-six cases of SIDS occurred among 38 infants dying under 6 months of age in a cohort of 27,000 infants studied prospectively to characterize their sleep-wake behavior. 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. At autopsy, brainstem material was collected and immunohistochemistry for Ki-67 was carried out. The density of Ki-67-positive neurons was measured semiquantitatively. Correlation analyses were carried out between the density of Ki-67-positive neurons and the data on sleep apnea. RESULTS: Except in two cases in SIDS victims and in one control, the detection of Ki-67 was negative. No correlation analysis between the Ki-67 and of sleep apnea was found. CONCLUSIONS: There were no abnormal cell kinetics detected by the demonstration of Ki-67 antigen in the brainstems of SIDS victims.

The relationship between neuronal plasticity and serotonergic neurons in the brainstem of SIDS victims.

BACKGROUND: The sudden infant death syndrome (SIDS) is still the main cause of postneonatal infant death and its cause is still unknown. Recently, the medullary serotonergic network deficiency theory has been proposed and an association between SIDS and neuronal plasticity has also been suggested. The growth-associated phosphoprotein 43 (GAP43) is a marker of synaptic plasticity and is critical for normal development of the serotonergic innervation. Therefore, the characteristics of GAP43-positive elements and their association with serotonergic neurons were here investigated in the brainstem of SIDS victims. MATERIALS AND METHODS: The materials of this study included 26 cases of SIDS and 12 control cases. The brainstem material was collected and the immunohistochemistry of GAP43 and tryptophan hydroxylase (TrypH) carried out. The density of GAP43-positive neurons and dendrites and of TrypH-positive neurons were measured quantitatively. Nonparametric analyses of GAP43 between SIDS and non-SIDS and correlation analyses between GAP43 and TrypH were performed. RESULTS: No significant difference in GAP43-associated findings was found between SIDS and non-SIDS nor any significant correlation between GAP43-associated findings and TrypH-positive neurons. CONCLUSIONS: The results of this study were not in agreement with the association of GAP43 with SIDS and with serotonergic innervation in SIDS.

Catecholaminergic neurons in the brain-stem and sleep apnea in SIDS victims.

BACKGROUND: Tyrosine hydroxylase (TH) is a specific marker for catecholaminergic neurones. Some reports have demonstrated a decrease of TH in the Sudden Infant Death Syndrome (SIDS) compared with controls. To further investigate this, the correlation between TH and sleep apnea was investigated here. MATERIALS AND METHODS: 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 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 the duration of sleep apnea were analyzed. The brain stem material was collected and subjected to immunohistochemical studies for TH. The density of TH-immunoreactive neurons was measured in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguous and the ventrolateral medulla (VLM) in the medulla oblongata. Correlation analyses were carried out between the density of TH-immunoreactive neurons and the data from the sleep apnea studies. RESULTS: There was no SIDS specific correlation between TH-immunoreactive neurons in the nucleus hypoglossus, nervus vagus dorsalis, solitary and ambiguous and the ventrolateral medulla (VLM) in the medulla oblongata and the frequency and duration of sleep apnea. CONCLUSIONS: No significant association between the pathological data and the physiological data refers to TH positive neurons in the medulla oblongata in SIDS victims.

Substance P in the midbrains of SIDS victims and its correlation with sleep apnea.

BACKGROUND: Substance P (SP) is a neuropeptide transmitter found in sensory neurons of the central nervous system and related to pain sensation and respiratory regulation. Some reports claim an increase in SP in the brains of SIDS victims, so the correlation between SP and sleep apnea was investigated here. 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 Sudden Infant Death Syndrome (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. Brainstem material was collected and immunohistochemistry for SP was carried out. The density of SP positive fibers was measured in the nucleus spinal and mesencephalic nervi trigemini and nucleus parabranchialis in the brainstem of abovementioned cases. Correlation analyses were carried out between the density of SP and the data of sleep apnea. RESULTS: There was no SIDS specific correlation of SP through the above-listed parts of the midbrain with frequency and duration of sleep apnea. CONCLUSIONS: There was no significant association between the SP findings and apnea data in SIDS; this is not in agreement with the association of apnea in pathophysiology of SIDS.

Serotonergic receptors in the midbrain correlated with physiological data on sleep apnea in SIDS victims.

BACKGROUND: Recently it has been reported that serotonin and related matters are associated with the sudden infant death syndrome (SIDS), which is still the main cause of postneonatal infant death. To further explore this claim, the correlation between serotonin receptors in the brainstem and sleep apnea in SIDS victims 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 including 26 cases of SIDS. 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 apnea were analyzed. Brainstem material was collected and immunohistochemistry on 5-hydroxy tryptamine 1A (5HT1A) receptor was carried out. The density of 5HT1A receptor-positive neurons was measured quantitatively. Nonparametric analysis of the density of 5HT1A receptor-positive neurons was carried out between SIDS and non-SIDS cases. Correlation analyses were performed between the density of 5HT1A receptor-positive neurons and the data on sleep apnea. RESULTS: There was no correlation between the pathological data on 5HT1A receptors and the physiological data on sleep apnea in SIDS victims. CONCLUSIONS: No correlation between pathological findings of serotonin and physiological findings of sleep apnea were not in agreement with the association of sleep apnea in pathophysiology of SIDS.

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.

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.

Posttraumatic stress disorder after dog bites in children.

Of 22 children who were victims of dog bite, 12 had symptoms of posttraumatic stress disorder 2 to 9 months after the bite. Violent dog attacks inflicting multiple and/or deep wounds were associated with risk of posttraumatic stress disorder.