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1.
Otolaryngol Clin North Am ; 57(3): 407-419, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38575485

RESUMO

Obstructed breathing is the most common indication for tonsillectomy in children. Although tonsillectomy is performed frequently worldwide, the surgery is associated with a number of significant complications such as bleeding and respiratory failure. Complication risk depends on a number of complex factors, including indications for surgery, demographics, patient comorbidities, and variations in perioperative techniques. While polysomnography is currently accepted as the gold standard diagnostic tool for obstructive sleep apnea, studies evaluating outcomes following surgery suggest that more research is needed on the identification of more readily available and accurate tools for the diagnosis and follow-up of children with obstructed breathing.


Assuntos
Adenoidectomia , Polissonografia , Apneia Obstrutiva do Sono , Tonsilectomia , Humanos , Apneia Obstrutiva do Sono/cirurgia , Apneia Obstrutiva do Sono/diagnóstico , Tonsilectomia/métodos , Tonsilectomia/efeitos adversos , Adenoidectomia/métodos , Adenoidectomia/efeitos adversos , Criança , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
2.
Neurobiol Dis ; 188: 106319, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37813167

RESUMO

Amongst other molecules, the cholinergic system consists of choline-acetyltransferase (ChAT, - synthesis enzyme), acetylcholinesterase (AChE - primary hydrolysis enzyme), and butyrylcholinesterase (BuChE - secondary hydrolysis enzyme). In the brainstem, the Dorsal Motor Nucleus of The Vagus (DMNV) has high cholinergic expression and is a region of interest in the neuropathology of sudden infant death syndrome (SIDS). SIDS is the unexpected death of a seemingly healthy infant, but postmortem brainstem abnormalities suggesting altered cholinergic regulation have been found. This study aimed to determine the percentage of positive ChAT and AChE neurons within the infant DMNV through immunohistochemistry at the three levels of the brainstem medulla (caudal, intermediate, and rostral), to investigate whether the proportion of neurons positive for these enzymes differs amongst the diagnostic subgroups of SIDS compared to those with an explained cause of Sudden unexpected death in infancy (eSUDI), and whether there were any associations with SIDS risk factors (male gender, cigarette smoke exposure, co-sleeping/bed sharing, and prone sleeping). Results showed that ChAT-positive neurons were lower in the rostral DMNV in the SIDS II cohort, and within the caudal and intermediate DMNV of infants who were exposed to cigarette smoke. These findings suggest altered cholinergic regulation in the brainstem of SIDS infants, with potential contribution of cigarette smoke exposure, presumably via the nicotinic acetylcholinergic receptor system.


Assuntos
Acetilcolinesterase , Morte Súbita do Lactente , Humanos , Lactente , Masculino , Butirilcolinesterase , Colina , Colina O-Acetiltransferase , Colinérgicos
3.
Mol Neurobiol ; 60(7): 4120-4131, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37041306

RESUMO

The role of the lateral geniculate nucleus (LGN) in vision has been extensively studied, yet its extraretinal capacities are still being investigated, including its role in arousal from sleep. The ß2 nicotinic acetylcholine receptor (nAChR) subunit is involved in the laminal organisation of the LGN with magnocellular (MC) and parvocellular (PC) neurons. Sudden infant death syndrome (SIDS) occurs during a sleep period and, neuropathologically, is associated with increased neuronal cell death and altered nAChRs. A recent qualitative pilot study from our group implicates the possibility of increased neuronal death/apoptosis in the SIDS LGN. The present study used quantitative analysis to report the baseline expression of apoptotic and nAChR subunits α7 and ß2 in the PC and MC layers of the LGN, to determine correlations amongst these markers within layers and across layers, and to evaluate changes in the expression of these markers in the LGN of SIDS infants, along with associations with SIDS risk factors, such as age, sex, cigarette smoke exposure, bed-sharing, and presence of an upper respiratory tract infection (URTI). Tissue was immunohistochemically stained for cell death markers of active caspase-3 (Casp-3) and TUNEL, and for the α7 and ß2 nAChR subunits. Amongst 43 cases of sudden and unexpected deaths in infancy (SUDI), classifications included explained deaths (eSUDI, n = 9), SIDS I (n = 5) and SIDS II (n = 29). Results indicated a strong correlation of the apoptotic markers and ß2 nAChR subunit between the LGN layers, but not across the markers within the layers. Amongst the diagnostic groups, compared to eSUDI, the SIDS II cases had decreased Casp-3 expression while ß2 nAChR expression was increased in both PC and MC layers. Amongst the SIDS risk factors, URTI and bed-sharing were associated with changes in neuronal death but not in the α7 and ß2 markers. In conclusion, our findings do not support a role for the α7 and ß2 nAChRs in apoptotic regulation of the LGN layers during infancy. However, for SIDS victims, an inverse correlation between the changes for markers of apoptosis and the ß2 nAChR subunit expression suggests altered LGN function.


Assuntos
Receptores Nicotínicos , Morte Súbita do Lactente , Lactente , Humanos , Corpos Geniculados/química , Corpos Geniculados/metabolismo , Projetos Piloto , Receptores Nicotínicos/metabolismo , Morte Celular , Receptor Nicotínico de Acetilcolina alfa7/metabolismo
4.
Plast Reconstr Surg Glob Open ; 11(2): e4819, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36845867

RESUMO

Previous studies suggest that infants with Robin sequence show a pattern of steady improvement in the severity of airway obstruction, and of their treatment requirements, during infancy. Methods: Three infants with Robin sequence and severe obstructive sleep apnea were managed with nasal continuous positive airways pressure (CPAP). Multiple measures of airway obstruction were made during infancy, including CPAP pressure evaluations and sleep studies (screening and polysomnography studies). Parameters reported include obstructive apnea-hypopnea index, oxygen desaturation parameters, and CPAP pressures required for effective airway management. Results: CPAP pressure requirements increased in all three infants during their first weeks of life. Apnea indices on polysomnography did not track with the CPAP pressure requirements. Peak pressure requirements were at 5 and 7 weeks for two patients, with subsequent gradual decline and cessation of therapy CPAP at 39 and 74 weeks, respectively. The third patient had a complicated course, jaw distraction at 17 weeks, and biphasic CPAP pressure requirement (first peak at 3 weeks, but maximum pressure at 74 weeks), with cessation of CPAP at 75 weeks. Conclusions: The observed pattern of early increases in CPAP pressure requirements for infants with Robin sequence adds to the complexities of managing this disorder. Factors that may lead to this pattern of change in airway obstruction are discussed.

5.
Histochem Cell Biol ; 159(3): 247-262, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36422707

RESUMO

The majority of research regarding the expression of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the brain has been conducted using histochemistry to identify enzymatic activity in frozen fixed tissue. However, retrospective human neurochemistry studies are generally restricted to formalin-fixed, paraffin-embedded (FFPE) tissues that are not suitable for histochemical procedures. The availability of commercially available antibody formulations provides the means to study such tissues by immunohistochemistry (IHC). In this study, we optimised IHC conditions for evaluating the expression of AChE and BuChE in the brainstem, focusing on the dorsal motor nucleus of the vagus, in human and piglet FFPE tissues, using commercially available antibodies. Our results were compared to published reports of histochemically determined AChE and BuChE expression. We varied antibody concentrations and antigen retrieval methods, and evaluated different detection systems, with the overall aim to optimise immunohistochemical staining. The primary findings, consistent across both species, are: (1) AChE and BuChE expression dominated in the neuronal somata, specifically in the neuronal cytoplasm; and (2) no change in the protocol resulted in axonal/neuropil expression of AChE. These results indicate that IHC is a suitable tool to detect AChE and BuChE in FFPE tissue using commercial antibodies, albeit the staining patterns obtained differed from those using histochemistry in frozen tissue. The underlying cause(s) for these differences are discussed in detail and may be associated with the principal components of the staining method, the antibody protein target and/or limitations to the detection of epitopes by tissue fixation.


Assuntos
Acetilcolinesterase , Butirilcolinesterase , Animais , Humanos , Acetilcolinesterase/metabolismo , Anticorpos , Butirilcolinesterase/metabolismo , Formaldeído , Imuno-Histoquímica , Inclusão em Parafina , Estudos Retrospectivos , Suínos
6.
J Clin Sleep Med ; 19(2): 275-282, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36123956

RESUMO

STUDY OBJECTIVES: To determine baseline facial convexity measurements in children with obstructive sleep apnea (OSA) across the age spectrum. METHODS: Polysomnogram, stereophotogrammetry, and biometric data were collected from children aged 0-18 years who were being investigated for OSA. Analyses evaluated differences in facial convexity according to OSA severity and other sleep parameters, while adjusting for age, ethnicity, and sex. RESULTS: Ninety-one children, aged 0.05-16.02 years, met the inclusion criteria for this study. Initial analysis showed that the logarithm of age had a significant effect on facial convexity (P = 8.3·10-7) with significant effects of sex (P = 1.3·10-2), while excluding OSA. Ordinal logistic regression taking into consideration age, sex, weight, height, and ethnicity with OSA severity categorized as obstructive apnea-hypopnea index negative, mild, moderate, or severe showed that facial convexity was associated with OSA severity (P = 2.2·10-3); an increasing obtuse angle of convexity increased the tendency to be classified as having severe OSA. CONCLUSIONS: Using three-dimensional imaging, we found an added impact of infancy on changes of facial convexity with age. While modeling could describe facial convexity without any OSA-associated sleep parameters, differences in facial convexity were present among groups with different levels of OSA severity adjusted for growth (age, weight, and height), sex, and ethnicity. The method provides a safer and cheaper alternative to other medical imaging techniques in children and holds potential for future use in studies of craniofacial structure. CITATION: Tyler G, Machaalani R, Waters KA. Three-dimensional orthodontic imaging in children across the age spectrum and correlations with obstructive sleep apnea. J Clin Sleep Med. 2023;19(2):275-282.


Assuntos
Apneia Obstrutiva do Sono , Humanos , Criança , Apneia Obstrutiva do Sono/complicações , Sono , Face , Polissonografia , Diagnóstico por Imagem
7.
Neurotox Res ; 40(6): 1859-1868, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36322363

RESUMO

This study evaluated the expression of reelin, an extracellular protein involved in lamination and migration of neurons, in the hippocampus of young piglets, and quantified to examine the following: (i) baseline levels within layers of the hippocampus and dentate gyrus (DG); (ii) differences between ventral and dorsal hippocampi; and (iii) changes attributable to postnatal exposure to continuous nicotine for 12 days, or intermittent hypercapnic hypoxia (IHH), with further analysis according to duration of IHH (1 vs 4 days). Additionally, we analysed whether any exposure altered DG morphology and whether it is related to altered reelin expression. Reelin was visualised via immunohistochemistry, and the number of positive reelin cells/mm2 was measured in the CA4/Hilus, layers of the DG, and the CA1. The dorsal DG had significantly more reelin within the subgranular zone compared to the ventral DG (p < 0.01). There was no difference in reelin between nicotine (n = 5) and controls (n = 5). IHH exposed piglets (n = 10) had significantly lowered reelin in the CA1 (p = 0.05), specifically the stratum pyramidale (p = 0.04) and the hippocampal fissure (p = 0.02), compared to their controls (n = 7); the duration of IHH had no effect. No exposure was associated with an alteration in DG morphology. This study shows that postnatal IHH exposure decreased reelin expression in the developing piglet hippocampal CA1, suggesting that IHH may result in altered neuronal migration.


Assuntos
Hipocampo , Nicotina , Animais , Suínos , Nicotina/farmacologia , Hipocampo/metabolismo , Neurônios/metabolismo , Neurogênese , Hipóxia/metabolismo , Giro Denteado , Moléculas de Adesão Celular Neuronais/metabolismo , Proteínas da Matriz Extracelular/metabolismo
9.
Paediatr Respir Rev ; 44: 53-60, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34750067

RESUMO

The mechanism of death in Sudden infant death syndrome (SIDS) remains unknown but it is hypothesised that cardiorespiratory failure of brainstem origin results in early post-natal death. For a subset of SIDS infants, an underlying genetic cause may be present, and genetic abnormalities affecting brainstem respiratory control may result in abnormalities that are detectable before death. Genetic knockout mice models were developed in the 1990s and have since helped to elucidate the physiological roles of a number of genes. This systematic review aimed to identify which genes, when knocked out, result in the phenotypes of abnormal cardiorespiratory control and/or early post-natal death. Three major genes were identified: Pet1- a serotonin transcription factor, the neurotrophin pituitary adenylate cyclase activating polypeptide (PACAP) and its receptor (PAC1). Knockouts targeting these genes had blunted hypercapnic and/or hypoxic responses and early post-natal death. The hypothesis that these genes have a role in SIDS is supported by their being identified as abnormal in SIDS cohorts. Future research in SIDS cohorts will be important to determine whether these genetic abnormalities coexist and their potential applicability as biomarkers.


Assuntos
Morte Súbita do Lactente , Animais , Camundongos , Humanos , Morte Súbita do Lactente/genética , Camundongos Knockout , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Hipercapnia , Hipóxia/genética
10.
J Neuropathol Exp Neurol ; 81(1): 61-75, 2022 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-34865047

RESUMO

Morphological differences in the dentate gyrus (DG) have been reported in sudden unexpected deaths in infancy (SUDI), with the feature of focal granule cell (GC) bilamination (FGCB) reported as increased in unexplained SUDI, including sudden infant death syndrome (SIDS), compared with explained SUDI (eSUDI). However, it remains to be determined how these morphologies relate to each other and their extent along the anteroposterior length. This retrospective study evaluated the prevalence of FGCB, single or clustered ectopic GCs, granule cell dispersion (GCD), heterotopia, hyperconvolution, gaps, thinning, blood vessel dissection (BVD), and cuffing (BV cuffing), in an Australian SUDI cohort, and compared the prevalence of these features in eSUDI and unexplained SUDI. We analyzed 850 formalin-fixed paraffin-embedded serial and subserial sections of the hippocampus at the level of the lateral geniculate nucleus from 90 infants, and identified GCD in 97% of infants, single ectopic cells, hyperconvolution, thinning, and BVD in 60%-80%, heterotopia in 36%, gaps, clusters of ectopic cells and BV cuffing in 9%-15%, and FGCB in 18%. These features are clustered within 3-5 serial sections. The presence of FGCB correlated with single ectopic GCs and hyperconvolution. There were no differences in the prevalence of these features between unexplained SUDI (n = 74) and eSUDI (n = 16). Our findings highlight that DG morphological features are highly localized, extending 14-35 µm at their focal location(s) along the anteroposterior length. Consequently, multiple sections along the longitudinal extent are required to identify them. No feature differentiated SUDI from eSUDI in our cohort, thus we cannot conclude that any of these features are abnormal and it remains to be determined their functional significance.


Assuntos
Giro Denteado/patologia , Morte Súbita do Lactente/patologia , Austrália , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos
11.
Semin Fetal Neonatal Med ; 26(6): 101282, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34742665

RESUMO

Evaluation and management of airway obstruction in prone position were reviewed from studies in infants with micrognathia and/or cleft palate, using polysomnography (PSG) or similar measures, and comparing prone against other positions. Most studies identified were case series from specialist referral centres. Airway obstruction appears more severe on PSG than clinical assessment, but there is no consensus for PSG definitions of mild, moderate or severe airway obstruction. Infants show individual variability in responses to positioning; sleep quality tends to improve when prone, but 22-25% have better respiratory outcomes when supine. Most centres recommend home monitoring if advising that an infant be placed prone to manage their airway obstruction. In conclusion, in case series, success rates for managing infant airway obstruction by prone positioning vary from 12 to 76%. PSG studies comparing prone with other sleep positions can help differentiate which infants show improved airway obstruction and/or sleep quality when positioned prone.


Assuntos
Obstrução das Vias Respiratórias , Micrognatismo , Síndrome de Pierre Robin , Obstrução das Vias Respiratórias/terapia , Tratamento Conservador , Humanos , Lactente , Micrognatismo/terapia , Síndrome de Pierre Robin/complicações , Síndrome de Pierre Robin/terapia , Polissonografia
12.
Respirology ; 26(10): 920-937, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34387937

RESUMO

The goal of this position paper on ventilatory support at home for children is to provide expert consensus from Australia and New Zealand on optimal care for children requiring ventilatory support at home, both non-invasive and invasive. It was compiled by members of the Thoracic Society of Australia and New Zealand (TSANZ) and the Australasian Sleep Association (ASA). This document provides recommendations to support the development of improved services for Australian and New Zealand children who require long-term ventilatory support. Issues relevant to providers of equipment and areas of research need are highlighted.


Assuntos
Sono , Austrália , Criança , Consenso , Humanos , Nova Zelândia
13.
Pediatrics ; 148(2)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34257146

RESUMO

BACKGROUND AND OBJECTIVES: The Preschool Obstructive Sleep Apnea Tonsillectomy and Adenoidectomy study is a prospective randomized controlled study of children aged 3 to 5 years. This follow-up evaluated postoperative outcomes 24 months after randomization. METHODS: Baseline, 12-month, and 24-month assessments included intellectual ability, polysomnography, audiology, a pediatric sleep questionnaire, the parent rating scale of the Behavior Assessment System for Children, and the Behavior Rating Inventory of Executive Functioning. RESULTS: In total, 117 (55% male) of 190 children, 61.6% of those initially randomly assigned, attended 24-month follow-up; 62 of 99 were assigned T/A within 2 months (eT/A); and 55 of 91 were assigned to T/A after the 12-month follow-up (T/A12). Intellectual ability, our primary outcome, did not differ according to the timing of T/A. Exploratory analyses revealed changes in both groups after T/A, including fewer children having day sleeps (eT/A from baseline 97% to 11%, T/A12 from 36% at 12 months to 9%), improved symptom scores (eT/A 0.62 to 0.25, T/A12 0.61 to 0.26; P < .001), improved behavior T-scores (eT/A 71.0 to 59.9, T/A12 63.6 to 50.5; P < .001), and improved polysomnography (obstructive apnea-hypopnea index eT/A 1.9 to 0.3 per hour, T/A12 1.3 to 0.3; P < .001). The eT/A group revealed temporary postoperative improvement of Woodcock-Johnson III subscales (sound blending and incomplete word scores) and behavioral withdrawal. CONCLUSIONS: T/A for mild obstructive sleep apnea led to large improvements in sleep and behavior in preschool-aged children, regardless of the timing of surgery.


Assuntos
Comportamento Infantil , Apneia Obstrutiva do Sono/cirurgia , Sono , Tonsilectomia , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
14.
J Paediatr Child Health ; 57(12): 1923-1928, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34152048

RESUMO

AIM: Nocturnal enuresis (NE) and sleep-disordered breathing (SDB) are common in childhood. While the two disorders are linked, those links are still being clarified. METHODS: This study compared sleep profiles and enuresis-related behaviours between children with NE and those without, who were referred to a tertiary sleep unit with suspected SDB, using the combination of polysomnography (PSG) and questionnaire. Continuous numerical data were analysed after adjusting for body mass index z-score. RESULTS: The study included 52 Children (39 boys, 13 girls) aged 5-14 years. Twenty-one had enuresis (10 monosymptomatic enuresis (MNE) and 11 non-monosymptomatic enuresis (NMNE)) and 31 did not have enuresis. The majority had comorbidities. On PSG, all children with NE had moderate obstructive sleep apnoea (OSA) compared to the control group which were of mild OSA. Children with NMNE had a higher percentage time in stage-3 non-REM sleep when compared to the non-enuretic and MNE groups (P < 0.05). On the questionnaire, more parents of the NE groups reported that their child was 'difficult to wake in the morning' (P < 0.05). CONCLUSION: In this heterogeneous population referred for suspected SDB, children with NE had moderate OSA, yet those with MNE had increased arousals and more often report difficulty waking than children with suspected SDB who do not wet, while children with NMNE exhibit changes in sleep architecture suggesting deeper sleep. These differences may impact treatment choices for children with enuresis.


Assuntos
Enurese , Enurese Noturna , Feminino , Humanos , Masculino , Polissonografia , Respiração , Sono , Inquéritos e Questionários
15.
Appl Immunohistochem Mol Morphol ; 29(6): e46-e56, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33710124

RESUMO

Neuronal nuclei (NeuN) is a neuron-specific nuclear protein, reported to be stably expressed in most postmitotic neurons of the vertebrate nervous system. Reduced staining has been interpreted by some to indicate loss of cell viability in human studies, while others suggest this may be because of changes in the antigenicity of the target epitope. Preliminary studies in our laboratory found low immunostaining for the NeuN antibody on formalin fixed and paraffin embedded (FFPE) human brain tissue. We report on the techniques and results used to enhance the staining for NeuN in that tissue. In parallel, we stained NeuN in piglet brain tissue, sourced from an experimental model where methodological parameters, including those for tissue fixation and storage, were tightly controlled. In human FFPE brain tissue, we were unable to enhance NeuN immunostaining to a degree sufficient for cell counting. In contrast, we found consistently high levels of staining in the piglet brain tissue. We conclude that processes used for fixation and storage of human FFPE brain tissue are responsible for the reduced staining. These results emphasize that a cautionary approach should be taken when interpreting NeuN staining outcomes in human FFPE brain tissue.


Assuntos
Antígenos Nucleares/metabolismo , Hipocampo/metabolismo , Imuno-Histoquímica/métodos , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Fixação de Tecidos/métodos , Animais , Diferenciação Celular , Formaldeído , Hipocampo/patologia , Humanos , Neurônios/patologia , Inclusão em Parafina , Coloração e Rotulagem , Suínos
16.
Hippocampus ; 31(5): 493-502, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33539623

RESUMO

Reelin plays a key role in neuronal migration and lamination in the cortex and hippocampus. Animal studies have shown that reelin expression decreases with age. The aim of this study was to evaluate the expression of reelin in all layers of the human hippocampal formation across three age groups. We used immunohistochemistry in formalin fixed and paraffin embedded hippocampal tissue from infants (1-10 months; n = 9), children (4-10 years; n = 4), and adults (45-60 years; n = 6) to stain for reelin. Expression was quantified (measured as the number of positive reelin cells/mm2 ) in the granule cell layer of the dentate gyrus (DG), the molecular layer of the dentate gyrus (ML), the hippocampal fissure (HF), stratum lacunosum moleculare (SLM), CA4/Hilus and the stratum pyramidale layer of CA3, CA2, and CA1. Expression of reelin was highest in the HF irrespective of age, followed by the SLM and ML. Minimal to no expression was seen in the stratum pyramidale layer of CA1-3. With age, reelin expression decreased and was statistically significant from infancy to childhood in the HF (p = .02). This study confirms that reelin expression decreases with age in the human hippocampus, and shows for the first time that the major decrease occurs between infancy and early childhood.


Assuntos
Hipocampo , Proteínas do Tecido Nervoso , Animais , Córtex Cerebral/metabolismo , Pré-Escolar , Hipocampo/metabolismo , Humanos , Proteínas do Tecido Nervoso/metabolismo , Neurogênese , Neurônios/fisiologia
17.
Mol Neurobiol ; 58(5): 2242-2255, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33417217

RESUMO

Low orexin levels in the hypothalamus, and abnormal brainstem expression levels of many neurotransmitter and receptor systems in infants who died suddenly during a sleep period and diagnosed as sudden infant death syndrome (SIDS), may be linked to abnormal protein unfolding. We studied neuronal expression of the three unfolded protein response (UPR) pathways in the human infant brainstem, hypothalamus, and cerebellum: activating transcription factor 6 (ATF6), phosphorylated inositol-requiring enzyme 1 (IRE1), and phosphorylated protein-kinase (PKR)-like endoplasmic reticulum (ER) kinase (pPERK). Percentages of positively stained neurons were examined via immunohistochemistry and compared between SIDS (n = 28) and non-SIDS (n = 12) infant deaths. Further analysis determined the effects of the SIDS risk factors including cigarette smoke exposure, bed-sharing, prone sleeping, and an upper respiratory tract infection (URTI). Compared to non-SIDS, SIDS infants had higher ATF6 in the inferior olivary and hypoglossal nuclei of the medulla, higher pIRE1 in the dentate nucleus of the cerebellum, and higher pPERK in the cuneate nucleus and hypothalamus. Infants who were found prone had higher ATF6 in the hypoglossal and the locus coeruleus of the pons. Infants exposed to cigarette smoke had higher ATF6 in the vestibular and cuneate nuclei of the medulla. Infants who were bed-sharing had higher pPERK in the dorsal raphe nuclei of the pons and the Purkinje cells of the cerebellum. This study indicates that subgroups of SIDS infants, defined by risk exposure, had activation of the UPR in several nuclei relating to proprioception and motor control, suggesting that the UPR underlies the neuroreceptor system changes responsible for these physiological functions, leading to compromise in the pathogenesis of SIDS.


Assuntos
Cerebelo/metabolismo , Núcleo Dorsal da Rafe/metabolismo , Estresse do Retículo Endoplasmático/fisiologia , Morte Súbita do Lactente , Resposta a Proteínas não Dobradas/fisiologia , Fator 6 Ativador da Transcrição , Retículo Endoplasmático/metabolismo , Endorribonucleases/metabolismo , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Orexinas/metabolismo , Assistência ao Paciente , Fosforilação , Proteínas Serina-Treonina Quinases/metabolismo , Fatores de Risco
18.
Sleep Breath ; 25(3): 1625-1634, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33411186

RESUMO

PURPOSE: Sleep disordered breathing (SDB) in children is commonly described as a continuum from primary snoring (PS) to obstructive sleep apnea (OSA), based on apnea indices from polysomnography (PSG). This study evaluated the difference in neurocognitive and behavioral parameters, prior to treatment, in symptomatic pre-school children with PSG-diagnosed OSA and PS. METHODS: All children had positive Pediatric Sleep Questionnaire (PSQ) results and were deemed suitable for adenotonsillectomy by an ENT surgeon. Neurocognitive and behavioral data were analyzed in pre-school children at recruitment for the POSTA study (The Pre-School OSA Tonsillectomy Adenoidectomy Study). Data were compared between PS and OSA groups, with Obstructive Apnea-Hypopnea Index, OAHI < 1/h or 1-10/h, respectively. RESULTS: Ninety-one children were enrolled, including 52 with OSA and 39 with PS. Distribution of IQ (using Brief Intellectual Ability, BIA) was slightly skewed towards higher values compared with the reference population. No significant differences were found in neurocognitive or behavioral parameters for children with OSA versus those with PS. DISCUSSION: Neurocognitive and behavioral parameters were similar in pre-school children symptomatic for OSA, regardless of whether or not PSG diagnosed PS or OSA. Despite having identical symptoms, children with PS on PSG are often treated conservatively, whereas those with OSA on PSG are considered for adenotonsillectomy. This study demonstrates that, regardless of whether or not PS or OSA is diagnosed on PSG, symptoms, neurocognition, and behavior are identical in these groups. We conclude that symptoms and behavioral disturbances should be considered in addition to OAHI when determining the need for treatment. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials registration number ACTRN12611000021976.


Assuntos
Cognição/fisiologia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/fisiopatologia , Adenoidectomia , Austrália , Comportamento Infantil , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Masculino , Nova Zelândia , Polissonografia , Índice de Gravidade de Doença , Ronco/diagnóstico , Ronco/fisiopatologia , Inquéritos e Questionários , Tonsilectomia
19.
Int J Pediatr Otorhinolaryngol ; 138: 110331, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32911238

RESUMO

OBJECTIVES: Surgery of the aortic arch carries a risk of injury to the vagus and recurrent laryngeal nerves, particularly in a young child, as these structures lie in close proximity to aortic arch. This study aimed to determine the incidence, symptomatology and natural history of vocal cord dysfunction (VCD) following aortic arch reconstructive surgery through a median sternotomy approach. METHODS AND MATERIALS: Prospective assessment was performed of all consecutive newborns who underwent cardiac surgery for aortic arch surgery via median sternotomy between January 2016 and May 2017 at a tertiary paediatric hospital. All patients underwent post-operative flexible fibreoptic nasolaryngoscopy (FNL) after extubation to assess for the presence of vocal cord dysfunction (VCD). Those with VCD were re-examined at followup. A feeding assessment performed by speech pathologists (SPs) and a video fluoroscopic swallow study (VFSS) were also performed in those with VCD or feeding difficulties. RESULTS: A total of 35 newborns were included in the study. At initial review, left sided VCD was demonstrated in 65.7% of patients (n=23). Significant associations with VCD were younger age (3.0 versus 6.5 days, p=0.041) and a weak or absent cry (Relative Risk=16.4, 95%CI 3.8-47.8, p<0.001). 52.5% (n=11) of patients with VCD had evidence of aspiration on VFSS. There was no significant difference in intensive care unit stay or overall hospital stay between patients with VCD compared to those without (33.0 days vs 28.8 days, p=0.73; 52.5 vs 45.9, p=0.72.) Infants with either proven VCD or a weak cry were more likely to be discharged home with a nasogastric (NG) tube (RR=4.67, p= 0.048; RR=7.00 p=0.022 respectively). At followup after 106 days, complete resolution was seen in 100% patients with partial VCD and 61.5% with complete VCD. CONCLUSIONS: VCD is a common complication following neonatal aortic arch surgery, although most experience resolution of symptoms over time. The authors recommend post-operative laryngoscopy in all patients should be routine, and particularly those with a weak cry.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Paralisia das Pregas Vocais , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Humanos , Lactente , Recém-Nascido , Laringoscopia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Esternotomia/efeitos adversos , Paralisia das Pregas Vocais/epidemiologia , Paralisia das Pregas Vocais/etiologia , Prega Vocal/cirurgia
20.
Pediatr Pulmonol ; 55(10): 2773-2781, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32687262

RESUMO

INTRODUCTION: Pediatric sleep disordered breathing (SDB) is characterized by long periods of partial upper airway obstruction (UAO) with low apnea-hypopnea indices (AHI). By measuring snoring and stertor, Sonomat studies allow quantification of these periods of partial UAO. AIM: To determine whether transcutaneous CO2 (TcCO2 ) levels correlate with increasing levels of partial UAO and to examine patterns of ΔTcCo2 in the transitions from (a) wakefulness to sleep and (b) non-rapid eye movement (NREM) to rapid eye movement (REM) sleep. METHODS: This was a retrospective review of sleep studies in seven asymptomatic controls aged 7 to 12 years and 62 symptomatic children with suspected SDB and no comorbidities, aged 2 to 13 years. Both groups underwent overnight polysomnography, including continuous TcCO2 , at one of two pediatric hospitals in Sydney. Changes in carbon dioxide levels between wake to NREM (sleep onset) and NREM to REM sleep were evaluated using an all-night TcCO2 trace time-linked to a hypnogram. Paired Sonomat recordings were used to quantify periods of UAO in the symptomatic group. RESULTS: The ΔTcCO2 at sleep onset was greater in SDB children than controls and ΔTcCO2 with sleep onset correlated with the duration of partial obstruction (r = .60; P < .0001). Children with an increase in TcCO2 from NREM to REM had a higher number of snoring and stertor events compared to those in whom TcCO2 decreased from NREM to REM (91 vs 30 events/h; P = < .0001). CONCLUSIONS: In children without comorbidities, the measurement of TcCO2 during sleep correlates with indicators of partial obstruction.


Assuntos
Obstrução das Vias Respiratórias/diagnóstico , Dióxido de Carbono/metabolismo , Síndromes da Apneia do Sono/diagnóstico , Adolescente , Obstrução das Vias Respiratórias/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Polissonografia , Estudos Retrospectivos , Sono/fisiologia , Síndromes da Apneia do Sono/metabolismo , Ronco/metabolismo
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