Nocturnal Oximetry-based Evaluation of Habitually Snoring Children.

RATIONALE: The vast majority of children around the world undergoing adenotonsillectomy for obstructive sleep apnea-hypopnea syndrome (OSA) are not objectively diagnosed by nocturnal polysomnography because of access availability and cost issues. Automated analysis of nocturnal oximetry (nSpO2), which is readily and globally available, could potentially provide a reliable and convenient diagnostic approach for pediatric OSA. METHODS: Deidentified nSpO2 recordings from a total of 4,191 children originating from 13 pediatric sleep laboratories around the world were prospectively evaluated after developing and validating an automated neural network algorithm using an initial set of single-channel nSpO2 recordings from 589 patients referred for suspected OSA. MEASUREMENTS AND MAIN RESULTS: The automatically estimated apnea-hypopnea index (AHI) showed high agreement with AHI from conventional polysomnography (intraclass correlation coefficient, 0.785) when tested in 3,602 additional subjects. Further assessment on the widely used AHI cutoff points of 1, 5, and 10 events/h revealed an incremental diagnostic ability (75.2, 81.7, and 90.2% accuracy; 0.788, 0.854, and 0.913 area under the receiver operating characteristic curve, respectively). CONCLUSIONS: Neural network-based automated analyses of nSpO2 recordings provide accurate identification of OSA severity among habitually snoring children with a high pretest probability of OSA. Thus, nocturnal oximetry may enable a simple and effective diagnostic alternative to nocturnal polysomnography, leading to more timely interventions and potentially improved outcomes.

The Perfect Storm: A Case of Rapid-Onset Obesity With Hypoventilation, Hypothalamic, Autonomic Dysregulation, Neuroendocrine Tumor (ROHHADNET) With Heart Failure, Narcolepsy, and a Rare Location of a Pelvic Neuroendocrine Tumor.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare disease of concurrent respiratory dysfunction and autonomic dysregulation with endocrine abnormalities. ROHHADNET includes ROHHAD plus coexisting neuroendocrine tumors (NETs). We describe an eight-year-old boy, who originally presented at four years of age with rapid weight gain and hyperhidrosis and who developed mild obstructive sleep apnea (OSA). His clinical course was eventually complicated by hypoxic respiratory failure requiring admission to the pediatric intensive care unit (PICU). Echocardiogram at that time demonstrated dilated cardiomyopathy left ventricular ejection fraction (LVEF) of 28% at time of admission. His respiratory failure persisted despite average volume-assured pressure support (AVAPS) around the clock leading to tracheostomy placement for cardiopulmonary support. He also demonstrated autonomic instability with multiple pituitary hormone deficiencies. Computed tomography (CT) imaging of the abdomen and pelvis demonstrated a presacral soft tissue mass consistent with a tumor of neural crest origin. Daytime somnolence and confusion progressed and a low cerebrospinal fluid hypocretin level revealed a diagnosis of narcolepsy type 1.

Exogenous erythropoietin administration attenuates intermittent hypoxia-induced cognitive deficits in a murine model of sleep apnea.

BACKGROUND: In rodents, exposure to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is associated with neurobehavioral impairments, increased apoptosis in the hippocampus and cortex, as well as increased oxidant stress and inflammation. Such findings are markedly attenuated in rodents exposed to sustained hypoxia 9SH) of similar magnitude. The hypoxia-sensitive gene erythropoietin (EPO) has emerged as a major endogenous neuroprotectant, and could be involved in IH-induced neuronal dysfunction. METHODS AND RESULTS: IH induced only transiently increased expression of EPO mRNA in hippocampus, which was continued in (SH)-exposed mice. IH, but not SH, adversely affected two forms of spatial learning in the water maze, and increased markers of oxidative stress. However, on a standard place training task, mice treated with exogenously administered EPO displayed normal learning, and were protected from the spatial learning deficits observed in vehicle-treated (C) littermates exposed to IH. Moreover, anxiety levels were increased in IH as compared to normoxia, while no changes in anxiety emerged in EPO-treated mice. Additionally, C mice, but not EPO-treated IH-exposed mice had significantly elevated levels of NADPH oxidase expression, as well as increased MDA and 8-OHDG levels in cortical and hippocampal lysates. CONCLUSIONS: The oxidative stress responses and neurobehavioral impairments induced by IH during sleep are mediated, at least in part, by imbalances between EPO expression and increased NADPH oxidase activity, and thus pharmacological agents targeting EPO expression in CNS may provide a therapeutic strategy in sleep-disordered breathing.

Stress, coping, and circadian disruption among women awaiting breast cancer surgery.

BACKGROUND: Psychological distress and coping related to a breast cancer diagnosis can profoundly affect psychological adjustment, possibly resulting in the disruption of circadian rest/activity and cortisol rhythms, which are prognostic for early mortality in metastatic colorectal and breast cancers, respectively. PURPOSE: This study aims to explore the relationships of cancer-specific distress and avoidant coping with rest/activity and cortisol rhythm disruption in the period between diagnosis and breast cancer surgery. METHODS: Fifty-seven presurgical breast cancer patients provided daily self-reports of cancer-specific distress and avoidant coping as well as actigraphic and salivary cortisol data. RESULTS: Distress and avoidant coping were related to rest/activity rhythm disruption (daytime sedentariness, inconsistent rhythms). Patients with disrupted rest/activity cycles had flattened diurnal cortisol rhythms. CONCLUSIONS: Maladaptive psychological responses to breast cancer diagnosis were associated with disruption of circadian rest/activity rhythms. Given that circadian cycles regulate tumor growth, we need greater understanding of possible psychosocial effects in cancer-related circadian disruption.

Increased incidence of pediatric narcolepsy following the 2009 H1N1 pandemic: a report from the pediatric working group of the sleep research network.

This study was aimed to evaluate the yearly incidence of pediatric narcolepsy prior to and following the 2009 H1N1 pandemic and to evaluate seasonal patterns of narcolepsy onset and associations with H1N1 influenza infection in the United States. This was a multicenter retrospective study with prospective follow-up. Participants were recruited from members of the Pediatric Working Group of the Sleep Research Network including 22 sites across the United States. The main outcomes were monthly and yearly incident cases of childhood narcolepsy in the United States, and its relationship to historical H1N1 influenza data. A total of 950 participants were included in the analysis; 487 participants were male (51.3%). The mean age at onset of excessive daytime sleepiness (EDS) was 9.6  ±â€… 3.9 years. Significant trend changes in pediatric narcolepsy incidence based on EDS onset (p  <  .0001) occurred over the 1998-2016 period, peaking in 2010, reflecting a 1.6-fold increase in narcolepsy incidence. In addition, there was significant seasonal variation in narcolepsy incident cases, with increased cases in spring (p  <  .05). Cross-correlation analysis demonstrated a significant correlation between monthly H1N1 infection and monthly narcolepsy incident cases (p  =  .397, p  <  .0001) with a lag time of 8 months. We conclude that there is a significant increase in pediatric narcolepsy incidence after the 2009 H1N1 pandemic in the United States. However, the magnitude of increase is lower than reported in European countries and in China. The temporal correlation between monthly H1N1 infection and monthly narcolepsy incidence, suggests that H1N1 infection may be a contributing factor to the increased pediatric narcolepsy incidence after the 2009 H1N1 pandemics.

Transcriptional landscape of bone marrow-derived very small embryonic-like stem cells during hypoxia.

BACKGROUND: Hypoxia is a ubiquitous feature of many lung diseases and elicits cell-specific responses. While the effects of hypoxia on stem cells have been examined under in vitro conditions, the consequences of in vivo oxygen deprivation have not been studied. METHODS: We investigated the effects of in vivo hypoxia on a recently characterized population of pluripotent stem cells known as very small embryonic-like stem cells (VSELs) by whole-genome expression profiling and measuring peripheral blood stem cell chemokine levels. RESULTS: We found that exposure to hypoxia in mice mobilized VSELs from the bone marrow to peripheral blood, and induced a distinct genome-wide transcriptional signature. Applying a computationally-intensive methodology, we identified a hypoxia-induced gene interaction network that was functionally enriched in a diverse array of programs including organ-specific development, stress response, and wound repair. Topographic analysis of the network highlighted a number of densely connected hubs that may represent key controllers of stem cell response during hypoxia and, therefore, serve as putative targets for altering the pathophysiologic consequences of hypoxic burden. CONCLUSIONS: A brief exposure to hypoxia recruits pluripotent stem cells to the peripheral circulation and actives diverse transcriptional programs that are orchestrated by a selective number of key genes.

Sleep assessments in healthy school-aged children using actigraphy: concordance with polysomnography.

Actigraphic (ACT) recordings are used widely in schoolchildren as a less intrusive and more extended approach to evaluation of sleep problems. However, critical assessment of the validity and reliability of ACT against overnight polysomnography (NPSG) are unavailable. Thus, we explored the degree of concordance between NPSG and ACT in school-aged children to delineate potential ACT boundaries when interpreting pediatric sleep. Non-dominant wrist ACT was recorded simultaneously with NPSG in 149 healthy school-aged children (aged 4.1-8.8 years, 41.7% boys, 80.4% Caucasian) recruited from the community. Analyses were limited to the Actiware (MiniMitter-64) calculated parameters originating from 1-min epoch sampling and medium sensitivity threshold value of 40; i.e. sleep period time (SPT), total sleep time (TST) and wake after sleep onset (WASO). SPT was not significantly different between ACT and NPSG. However, ACT underestimated TST significantly by 32.2±33.4 min and overestimated WASO by 26.3±34.4 min. The decreased precision of ACT was also evident from moderate to small concordance correlation coefficients (0.47 for TST and 0.09 for WASO). ACT in school-aged children provides reliable assessment of sleep quantity, but is relatively inaccurate during determination of sleep quality. Thus, caution is advocated in drawing definitive conclusions from ACT during evaluation of the sleep-disturbed child.

Transcriptomic analysis identifies phosphatases as novel targets for adenotonsillar hypertrophy of pediatric obstructive sleep apnea.

RATIONALE: Obstructive sleep apnea (OSA) is a highly prevalent disorder in children, in which enlarged adenotonsillar tissues (AT) play a major pathophysiologic role. Mechanisms leading to the proliferation and hypertrophy of AT in children who subsequently develop OSA remain unknown, and surgical extirpation of AT is associated with potential morbidity and mortality. OBJECTIVES: We hypothesized that a computationally based analysis of gene expression in tonsils from children with OSA and children with recurrent tonsillitis without OSA can identify putative mechanistic pathways associated with tonsillar proliferation and hypertrophy in OSA. METHODS: Palatine tonsils from children with either polysomnographically documented OSA or recurrent infectious tonsillitis were subjected to whole-genome microarray and functional enrichment analyses followed by significance score ranking based on gene interaction networks. The latter enabled identification and confirmation of a candidate list of tonsil-proliferative genes in OSA. MEASUREMENTS AND MAIN RESULTS: In vitro studies using a mixed tonsil cell culture system targeting one of these candidates, phosphoserine phosphatase, revealed that it was more abundantly expressed in tonsils of children with OSA, and that pharmacological inhibition of phosphoserine phosphatase led to marked reductions in T- and B-lymphocyte cell proliferation and increased apoptosis. CONCLUSIONS: A systems biology approach revealed a restricted set of candidate genes potentially underlying the heightened proliferative properties of AT in children with OSA. Furthermore, functional studies confirm a novel role for protein phosphatases in AT hypertrophy, and may provide a promising strategy for discovery of novel, nonsurgical therapeutic targets in pediatric OSA.

Intermittent hypoxia mobilizes bone marrow-derived very small embryonic-like stem cells and activates developmental transcriptional programs in mice.

BACKGROUND: obstructive sleep apnea is a prevalent disorder associated with cognitive dysfunction and cardiovascular and metabolic morbidity and is characterized by recurrent episodes of hypoxia during sleep. Bone marrow-derived very small embryonic-like (VSEL) pluripotent stem cells represent a recruitable pool that may play an important role in organ repair after injury. We hypothesized that exposure to intermittent hypoxia (IH) can mobilize VSELs from the bone marrow (BM) to peripheral blood (PB) in mice and can activate distinct transcriptional programs. METHODS: adult mice were exposed to IH or normoxia for 48 hours. VSELs were sorted from BM and PB using flow cytometry. Plasma levels of stem cell chemokines, stromal cell derived factor-1 (SDF-1), hepatocyte growth factor (HGF), and leukemia inhibitory factor (LIF) were measured. Transcriptional profiling of VSELs was performed, and differentially expressed genes were mapped to enriched functional categories and genetic networks. RESULTS: exposure to IH elicited migration of VSELs from BM to PB and elevations in plasma levels of chemokines. More than 1100 unique genes were differentially expressed in VSELs in response to IH. Gene Ontology and network analysis revealed the activation of organ-specific developmental programs among these genes. CONCLUSIONS: exposure to IH mobilizes VSELs from the BM to PB and activates distinct transcriptional programs in VSELs that are enriched in developmental pathways, including central nervous system development and angiogenesis. Thus, VSELs may serve as a reserve mobile pool of pluripotent stem cells that can be recruited into PB and may play an important role in promoting end-organ repair during IH.

Increased cellular proliferation and inflammatory cytokines in tonsils derived from children with obstructive sleep apnea.

Adenotonsillar hypertrophy is the major pathophysiological mechanism underlying obstructive sleep apnea (OSA) and recurrent tonsillitis (RI) in children. The increased expression of various mediators of the inflammatory response in tonsils of patients with OSA prompted our hypothesis that the enhanced local and systemic inflammation in children with OSA would promote tonsillar proliferation. Mixed cell cultures from tonsils recovered during adenotonsillectomy in children with OSA and RI were established, and proliferative rates were assessed. Cells were also cultured to determine the levels of proinflammatory cytokines and antioxidant protein levels and mRNA expression. Global cell proliferative rates from OSA tonsils were significantly higher than RI (p < 0.01), with CD3, CD4, and CD8 cell proliferation being higher in OSA (p < 0.05). Moreover, proinflammatory cytokines, such as TNF-alpha, IL-6, and IL-1alpha, were highly expressed in OSA-derived tonsils. Furthermore, thioredoxin (TRX), an antioxidant protein, was also highly expressed in OSA tonsils at the mRNA and protein levels (p < 0.01). Thus, T cells are in a highly proliferative state in the tonsils of children with OSA and are associated with increased production of proinflammatory cytokines and TRX, when compared with children with RI.

Green tea catechin polyphenols attenuate behavioral and oxidative responses to intermittent hypoxia.

RATIONALE: The intermittent hypoxia (IH) that characterizes sleep-disordered breathing impairs spatial learning and increases NADPH oxidase activity and oxidative stress in rodents. We hypothesized that green tea catechin polyphenols (GTPs) may attenuate IH-induced neurobehavioral deficits by reducing IH-induced NADPH oxidase expression, lipid peroxidation, and inflammation. OBJECTIVES: To assess the effects of GTP administered in drinking water on the cognitive, inflammatory, and oxidative responses to long-term (>14 d) IH during sleep in male Sprague-Dawley rats. METHODS: Cognitive assessments were conducted in the Morris water maze. We measured levels and expression of malondialdehyde (MDA), prostaglandin E(2), p47(phox) subunit of NADPH oxidase, receptor for advanced glycation end products (RAGE), and glial fibrillary acidic protein expression in rodent brain tissue. MEASUREMENTS AND MAIN RESULTS: GTP treatment prevented IH-induced decreases in spatial bias for the hidden platform during the Morris water maze probe trails as well as IH-induced increases in p47phox expression within the hippocampal CA1 region. In untreated animals, IH exposure was associated with doubling of cortical MDA levels in comparison to room air control animals, and GTP-treated animals exposed to IH showed a 40% reduction in MDA levels. Increases in brain RAGE and glial fibrillary acidic protein expression were observed in IH-exposed animals, and these increases were attenuated in animals treated with GTP. CONCLUSIONS: Oral GTP attenuates IH-induced spatial learning deficits and mitigates IH-induced oxidative stress through multiple beneficial effects on oxidant pathways. Because oxidative processes underlie neurocognitive deficits associated with IH, the potential therapeutic role of GTP in sleep-disordered breathing deserves further exploration.

Network analysis of temporal effects of intermittent and sustained hypoxia on rat lungs.

UNLABELLED: The molecular networks underlying the lung response to hypoxia are not fully understood. We employed systems biology approaches to study temporal effects of intermittent or sustained hypoxia on gene expression in rat lungs. We obtained gene expression profiles from rats exposed to intermittent or sustained hypoxia lasting 0-30 days and identified differentially expressed genes, their patterns, biological processes, and regulatory networks critical for lung response to intermittent or sustained hypoxia. We validated selected genes with quantitative real-time PCR. Intermittent and sustained hypoxia induced two distinct sets of genes in rat lungs that displayed different temporal expression patterns. Intermittent hypoxia induced genes mostly involved in ion transport and homeostasis, neurological processes, and steroid hormone receptor activity, while sustained hypoxia induced genes principally participating in immune responses. The intermittent hypoxia-activated network suggested a role for cross talk between estrogen receptor 1 (ESR1) and other key proteins in hypoxic responses. The sustained hypoxia-activated network was indicative of vascular remodeling and pulmonary hypertension. We confirmed the temporal expression changes of 12 genes (including the Esr1 gene and 4 ESR1 target genes) in intermittent hypoxia and 8 genes in sustained hypoxia with quantitative real-time PCR. CONCLUSIONS: intermittent and sustained hypoxia induced distinct gene expression patterns in rat lungs. The functional characteristics of genes activated by these two distinct perturbations suggest their roles in the downstream physiological effects of intermittent and sustained hypoxia. Our results demonstrate the discovery potential of applying systems biology approaches to the understanding of mechanisms underlying hypoxic lung response.

Obstructive sleep apnea and endothelial function in school-aged nonobese children: effect of adenotonsillectomy.

BACKGROUND: Obstructive sleep apnea (OSA) in children is associated with cardiovascular morbidity such as systemic and pulmonary hypertension. However, it remains unclear whether endothelial dysfunction occurs in pediatric OSA and whether it is reversible on effective treatment of OSA. METHODS AND RESULTS: Consecutive nonobese children (aged 6 to 11 years) who were diagnosed with OSA after overnight polysomnography and control children matched on the basis of age, gender, ethnicity, and body mass index underwent blood draw the next morning for soluble CD40 ligand, asymmetric dimethylarginine (ADMA), and nitrotyrosine levels, as well as 2 iterations of 60-second cuff-occlusion tests for assessment of endothelial function. These tests were repeated 4 to 6 months after adenotonsillectomy. OSA children showed blunted reperfusion kinetics after release of occlusion, which completely normalized in 20 of 26 patients after adenotonsillectomy. All 6 children in whom no improvements occurred had a strong family history of cardiovascular disease (versus 2 of the remaining 20 patients; P<0.04). Plasma nitrotyrosine and ADMA levels were similar in OSA and control children; however, soluble CD40 ligand levels were higher in OSA children and were reduced after treatment, particularly in those with normalized hyperemic responses. CONCLUSIONS: Postocclusive hyperemia is consistently blunted in children with OSA, and such altered endothelial function is reversible 4 to 6 months after treatment, particularly if a family history of cardiovascular disease is not present. Although no evidence for either nitric oxide-dependent oxidative/nitrosative stress or for the increased presence of the circulating nitric oxide synthase inhibitor ADMA was found in children with OSA, soluble CD40 ligand levels were increased in OSA and reflected the changes in endothelial function after treatment.

Prevalence of epileptiform activity in healthy children during sleep.

BACKGROUND: The term epileptiform discharge typically refers to interictal paroxysmal activity that occurs more commonly during sleep. This type of paroxysmal activity does not include the electroencephalographic (EEG) activity observed during a seizure. The prevalence of epileptiform activity in the general pediatric population is unknown. METHODS: Polysomnographic (PSG) studies were conducted in otherwise healthy children recruited from the general population and with no previous history of seizures or any other medical conditions. All sleep studies included an eight-lead EEG montage. Spike and sharp waves, either alone or accompanied by slow waves, occurring singly or in bursts lasting <5s were considered as representing epileptiform activity. RESULTS: Nine hundred seventy children underwent overnight PSG. In 14 children, evidence of epileptiform activity, in the absence of any additional abnormality in the PSG, occurred. Thus, the prevalence of epileptiform activity was 1.45%. Epileptiform patterns found were either spike or spike and wave and were more prominent during non-rapid eye movement (NREM) sleep, with 11 patients presenting spike and spike and wave patterns in the centro-temporal regions. Four of the six children who underwent neurocognitive tests exhibited abnormal findings in areas of behavior, attention, hyperactivity, and learning. CONCLUSION: Epileptiform activity in otherwise healthy children from the community is relatively frequent and, if confirmed by prospective studies, could be associated with suboptimal cognitive and behavioral functions. Increased awareness by sleep professionals and use of PSG montage that includes temporal leads and >2 standard EEG leads should facilitate the detection of epileptiform activity in children.

Prevalence of recurrent otitis media in habitually snoring school-aged children.

INTRODUCTION: The pathophysiology of obstructive sleep apnea (OSA) and recurrent otitis media (ROM) is intimately associated with the presence of adenotonsillar hypertrophy in children. However, it remains unclear whether habitually snoring children have a higher prevalence of ROM and whether they require tympanostomy tube placement more frequently. METHODS: Questionnaires collected from parental surveys of 5- to 7-year-old children attending the public schools in Louisville, KY were retrospectively reviewed for the presence of habitual snoring (HS), ROM, and the need for tympanostomy tube insertion. RESULTS: There were 16,321 surveys with complete datasets (51.2% boys; 18.6% African American (AA) with a mean age of 6.2+/-0.7 years). Of these children, 1844 (11.3%) were HS (53% boys; 25.9% AA); and, of these, 827 HS had also a positive history of ROM (44.8%) with a slight predominance in males (55%). In addition, 636 of these children underwent placement of tympanostomy tubes (i.e., 34.4% of all HS and 76.9% of ROM). Among the 14,477 non-snoring children (NS), ROM was reported in 4247 NS children (29.3%; p<0.000001; odds ratio [OR]: 1.95; confidence interval [CI]: 1.77-2.16) of which 57.6% were boys, and 1969 NS with ROM underwent tympanostomy tube placement (i.e., 46.3% of those with ROM and 13.6% of all non-snoring children). Thus, the risk for tympanostomy tube placement was also greater among HS compared to NS children (p<0.00001; OR: 2.19; CI: 1.98-2.43). CONCLUSIONS: Habitual snoring is associated with a significant increase in the prevalence of recurrent otitis media and the need for tympanostomy tube placement. Further studies aiming to assess the prevalence of obstructive sleep apnea among children with ROM are needed.

Nocturnal body position in sleeping children with and without obstructive sleep apnea.

OBJECTIVES: To assess whether body position during sleep differs among children with obstructive sleep apnea (OSAS) and controls, and to assess the effects of body position, obesity, and tonsillar size on respiratory disturbance. Four hundred and thirty consecutive children with polysomnographically demonstrated OSAS. And 185 age-, gender-, and ethnically matched children (Controls) were compared. The effect of sleep body position on respiratory disturbance was examined in OSAS, and also in relation to obesity and tonsillar size. Children with OSAS spent more time in the supine position than Controls (P<0.01), with less time spent in the side position (P<0.005). Obstructive apnea and hypopnea index (AHI) was similar in the three sleep-related positions, but apnea index (AI) was significantly greater (4.6 +/- 0.7/hr TST) in the supine position than in the side position (2.7 +/- 0.3/hr TST; P<0.001) or prone position (3.3 +/- 0.5/hr TST; P<0.01). Tonsillar size was not a contributing factor to positional differences in AI or AHI. Obese OSAS children had increased prone position (20.4 +/- 2.0%TST vs. non-obese: 10.9 +/- 2.5%TST; P<0.05), and displayed increased AHI and AI while supine. Non-obese OSAS increased AHI in prone or side positions compared to supine (P<0.01), with no significant differences in position-dependent AI. Children with OSAS spend more time sleeping supine and less time on the side. Obese children with OSAS are more likely to sleep prone, suggesting that this position may promote upper airway patency in the presence of obesity. Although tonsillar size is not associated with positional differences in breathing, the presence or absence of obesity markedly modifies the effect of body position on respiratory disturbance.

Epilepsy in 22q11.2 Deletion Syndrome: A Case Series and Literature Review.

BACKGROUND: The 22q11.2 deletion syndrome affects multiple organ systems, and the neurological manifestations are an important aspect of this disorder. Many are aware of cardiac anomalies associated with this uncommon genetic disorder. However, the different types of seizures, electroencephalography (EEG), and brain magnetic resonance imaging (MRI) findings seen in this condition are not appreciated. METHODS: Medical records of four patients with epilepsy due to 22q11.2 deletion syndrome were retrospectively reviewed for documentation of seizure types, EEG, and brain MRI findings. In addition, we also did a literature review of previously reported individuals with unprovoked seizures in this condition. RESULTS: A review of all published cases including our patients reveals that focal epilepsy (39 of 88, 44%) is the most common type followed by genetic generalized epilepsy (24 of 88, 27%). Diffuse cerebral atrophy and polymicrogyria were the most frequent MRI findings. CONCLUSIONS: Patients with structural brain abnormalities, especially polymicrogyria and associated epilepsy should have a chromosomal microarray (CMA) performed to screen for the 22q11.2 deletion syndrome. Focal epilepsy and genetic generalized epilepsy are the most frequent epilepsy types reported in this condition.

Intermittent hypoxia-induced cognitive deficits are mediated by NADPH oxidase activity in a murine model of sleep apnea.

BACKGROUND: In rodents, exposure to intermittent hypoxia (IH), a hallmark of obstructive sleep apnea (OSA), is associated with neurobehavioral impairments, increased apoptosis in the hippocampus and cortex, as well as increased oxidant stress and inflammation. Excessive NADPH oxidase activity may play a role in IH-induced CNS dysfunction. METHODS AND FINDINGS: The effect of IH during light period on two forms of spatial learning in the water maze and well as markers of oxidative stress was assessed in mice lacking NADPH oxidase activity (gp91phox(_/Y)) and wild-type littermates. On a standard place training task, gp91phox(_/Y) displayed normal learning, and were protected from the spatial learning deficits observed in wild-type littermates exposed to IH. Moreover, anxiety levels were increased in wild-type mice exposed to IH as compared to room air (RA) controls, while no changes emerged in gp91phox(_/Y) mice. Additionally, wild-type mice, but not gp91phox(_/Y) mice had significantly elevated levels of NADPH oxidase expression and activity, as well as MDA and 8-OHDG in cortical and hippocampal lysates following IH exposures. CONCLUSIONS: The oxidative stress responses and neurobehavioral impairments induced by IH during sleep are mediated, at least in part, by excessive NADPH oxidase activity, and thus pharmacological agents targeting NADPH oxidase may provide a therapeutic strategy in sleep-disordered breathing.

Sleep estimates in children: parental versus actigraphic assessments.

BACKGROUND: In the context of increasing awareness about the need for assessment of sleep duration in community and clinical settings, the use of questionnaire-based tools may be fraught with reporter bias. Conversely, actigraphy provides objective assessments of sleep patterns. In this study, we aimed to determine the potential discrepancies between parentally-based sleep logs and concurrent actigraphic recordings in children over a one-week period. METHODS: We studied 327 children aged 3-10 years, and included otherwise healthy, nonsnoring children from the community who were reported by their parents to be nonsnorers and had normal polysomnography, habitually-snoring children from the community who completed the same protocol, and children with primary insomnia referred to the sleep clinic for evaluation in the absence of any known psychiatric illness. Actigraphy and parental sleep log were concomitantly recorded during one week. RESULTS: Sleep logs displayed an average error in sleep onset after bedtime of about 30 minutes (P < 0.01) and of a few minutes before risetime in all groups. Furthermore, subjective parental reports were associated with an overestimated misperception of increased sleep duration of roughly one hour per night independent of group (P < 0.001). CONCLUSION: The description of a child's sleep by the parent appears appropriate as far as symptoms are concerned, but does not result in a correct estimate of sleep onset or duration. We advocate combined parental and actigraphic assessments in the evaluation of sleep complaints, particularly to rule out misperceptions and potentially to aid treatment. Actigraphy provides a more reliable tool than parental reports for assessing sleep in healthy children and in children with sleep problems.