Effectiveness of an intervention program on physical activity in children with narcolepsy type 1.

OBJECTIVES: Physical activity (PA) is recommended as part of the management of narcolepsy type 1 (NT1). This study aimed at 1) characterizing PA in children and adolescents treated for NT1 using objective and subjective measurements, 2) evaluating how PA is associated with NT1 symptoms and comorbidities, and 3) evaluating the effects of an Adapted Physical Activity (APA) program on PA and clinical characteristics. PATIENTS/METHODS: Patients with NT1 from the National Reference Center of Narcolepsy (Lyon, France) were consecutively included in an APA intervention protocol. Narcolepsy symptoms and comorbidities were collected using standardized questionnaires and sustained attention was evaluated using the Bron-Lyon Attention Stability Test before and after the four-week APA intervention. PA was measured objectively using actigraphy throughout the study. RESULTS: Twenty-seven NT1 patients were included (median age 14.7 years [8.3-18.4], cataplexy 88.9%, obesity 37.0%). At baseline, 52.4% of the patients had satisfactory PA levels according to international recommendations. Patients with leisure-time PA (LTPA) showed higher quality of life than patients without. 45% of the patients increased PA during the intervention compared to baseline. These responsive patients had more depressive feelings and tended to have lower objective PA than non-responsive patients at baseline. No significant correlation was found between PA levels before and during the intervention and other clinical data. CONCLUSIONS: Most children with NT1 showed satisfying PA levels despite their daytime sleepiness. LTPA engagement was associated with higher quality of life. An APA intervention could be effective in children with narcolepsy, especially for those with depressive feelings.

Gas exchange parameters for the prediction of obstructive sleep apnea in infants.

STUDY OBJECTIVES: Sleep laboratory polysomnography is the gold standard for obstructive sleep apnea (OSA) diagnosis in infants, but its access remains limited. Oximetry-capnography is another simple and widely used tool that can provide information on the presence of desaturations and alveolar hypoventilation. However, its reliability is debated. This study aimed at examining its use in determining OSA severity in infants. METHODS: This retrospective study was conducted in a sleep unit in a tertiary hospital in infants < 4 months old with clinical signs of OSA or Pierre Robin sequence who underwent a 1-night polysomnography coupled with oximetry-capnography. RESULTS: Among the 78 infants included (median [interquartile range] age: 61 [45-89] days at polysomnography), 44 presented with Pierre Robin sequence and 34 presented with isolated airway obstruction. The clinical, sleep, and respiratory characteristics were not significantly different between the 2 subgroups. In the entire cohort, 63.5% had severe OSA. The median obstructive apnea-hypopnea index was 14.5 (7.4-5.9) events/h, peripheral oxygen saturation (SpO2) was 97.4% (96.5-98.1%), and transcutaneous carbon dioxide pressure (PtcCO2) was 41.1 mmHg (38.3-44.9). The optimal threshold to predict an obstructive apnea-hypopnea index > 10 events/h was 6 events/h for an oxygen desaturation index ≥ 3% (sensitivity, 95.7%; specificity, 51.9%) and 2 events/h for an oxygen desaturation index ≥ 4% (sensitivity, 95.7%; specificity, 48.1%). CONCLUSIONS: Whereas transcutaneous capnography does not appear to be sufficient in predicting severe OSA in infants < 4 months old with Pierre Robin sequence or clinical signs of OSA, oximetry may be a useful alternative for the screening of severe OSA in infants in the absence of polysomnography. CITATION: Gyapay R, Ioan I, Thieux M, et al. Gas exchange parameters for the prediction of obstructive sleep apnea in infants. J Clin Sleep Med. 2024;20(7):1059-1067.

Does the brain sleep differently depending on intellectual abilities?

AIMS: To compare the children's sleep electroencephalogram according to their intellectual profile. METHODS: Children were grouped according to their Wechsler Intelligence Scale for Children (WISC) scores (17 with normal intelligence quotient [IQ, NIQ] and 24 with high IQ [HIQ]). Comparisons of spectral power between groups and its relationship with WISC scores were assessed using analyses of variance and linear regression models, adjusted for age and sex. RESULTS: Children with HIQ had more rapid eye movement (REM) sleep, especially late at night, and more power in slow-frequency bands during REM sleep than those with NIQ. There were also positive associations between the processing speed index and the spectral power in ß bands in NREM sleep, and with the spectral power in α, σ, ß, and γ bands in REM sleep, with different associations between groups. CONCLUSION: The enhanced power in slow bands during REM sleep in children with HIQ overlaps with that of typical REM sleep oscillations thought to be involved in emotional memory consolidation. The dissimilar relationships between spectral power and WISC scores in NIQ and HIQ groups may underlie functional differences in brain activity related to cognitive efficiency, questioning the direction of the relationship between sleep and cognitive functioning.

Salivary α-amylase as a marker of sleep disorders: A theoretical review.

Sleep disorders are commonplace in our modern societies. Specialized hospital departments are generally overloaded, and sleep assessment is an expensive process in terms of equipment, human resources, and time. Biomarkers would usefully complement current measures in the screening and follow-up of sleep disorders and their daytime repercussions. Among salivary markers, a growing body of literature suggests that salivary α-amylase (sAA) may be a cross-species marker of sleep debt. However, there is no consensus as to the direction of variation in sAA with sleep disorders. Herein, after describing the mechanisms of sAA secretion and its relationship with stress, studies assessing the relationship between sAA and sleep parameters are reviewed. Finally, the influence of confounding factors is discussed, along with methodological considerations, to better understand the fluctuations in sAA and facilitate future studies in the field.

Sleep Stage Transitions and Sleep-Dependent Memory Consolidation in Children with Narcolepsy-Cataplexy.

Electroencephalographic sleep stage transitions and altered first REM sleep period transitions have been identified as biomarkers of type 1 narcolepsy in adults, but not in children. Studies on memory complaints in narcolepsy have not yet investigated sleep-dependent memory consolidation. We aimed to explore stage transitions; more specifically altered REM sleep transition and its relationship with sleep-dependent memory consolidation in children with narcolepsy. Twenty-one children with narcolepsy-cataplexy and twenty-three healthy control children completed overnight polysomnography and sleep-dependent memory consolidation tests. Overnight transition rates (number of transitions per hour), global relative transition frequencies (number of transitions between a stage and all other stages/total number of transitions × 100), overnight transitions to REM sleep (transition from a given stage to REM/total REM transitions × 100), and altered first REM sleep period transitions (transitions from wake or N1 to the first REM period) were computed. Narcoleptic children had a significantly higher overnight transition rate with a higher global relative transition frequencies to wake. A lower sleep-dependent memory consolidation score found in children with narcolepsy was associated with a higher overnight transition frequency. As observed in narcoleptic adults, 90.48% of narcoleptic children exhibited an altered first REM sleep transition. As in adults, the altered sleep stage transition is also present in children with narcolepsy-cataplexy, and a higher transition rate could have an impact on sleep-dependent memory consolidation. These potential biomarkers could help diagnose type 1 narcolepsy in children more quickly; however, further studies with larger cohorts, including of those with type 2 narcolepsy and hypersomnia, are needed.

Metabolic disturbances in children with narcolepsy: a retrospective study.

STUDY OBJECTIVES: To determine the prevalence of metabolic syndrome (MS) in children with narcolepsy and to evaluate their clinical and sleep characteristics according to the different components of MS. METHODS: This retrospective study consisted of 58 de novo children with narcolepsy (median age: 12.7 years, 48.3% of boys). The recently published MS criteria in a French population of children were used. Clinical and sleep characteristics were compared between groups with different components of MS. RESULTS: MS was present in 17.2% of children with narcolepsy, among whom 79.3% presented with high homeostasis model assessment for insulin resistance (HOMA-IR), 25.9% with high body mass index, 24.1% with low high-density lipoprotein cholesterol (HDL-C), and 12.1% with high triglycerides. Patients with at least two MS components had more night eating behaviors and tended to have lower percentage of slow-wave sleep and more fragmented sleep. On multiple sleep latency test, they had shorter mean sleep latencies to rapid eye movement (REM), non-REM sleep and tended to have more sleep onset REM periods (SOREMPs) than those with less than two MS components. CONCLUSIONS: Insulin resistance was found to be the core metabolic disturbance in obese as well as in nonobese children with narcolepsy. Children with narcolepsy with at least two MS components presented a more severe daytime sleepiness and a higher prevalence of night-eating behaviors than those with less than two MS components. Such children might benefit from early evaluation and management in order to prevent future complications.

Obesity in children with narcolepsy: metabolic and endocrine comorbidities.

STUDY OBJECTIVES: Narcolepsy with cataplexy is associated with obesity in children. We proposed to assess whether metabolic complications were linked to narcolepsy regardless of obesity. The second aim of the study was to compare endocrine comorbidities in obese children with narcolepsy and control patients. METHODS: We performed a case-control study in Pediatric Sleep Unit and Pediatric Endocrinology Unit of Woman Mother Child Hospital (Lyon, France) comparing 22 children with narcolepsy with 22 sex-, pubertal stage-, and BMI-matched non-syndromic obese patients. Clinical examination, biological measurements including an oral glucose tolerance test, and abdominal ultrasound were performed. RESULTS: No difference regarding glucidic, lipid profile, hepatic, respiratory, and cardiovascular parameters were found between narcoleptic and control participants. Insulin sensitivity did not differ between the two groups. Control patients had more first-degree family history of overweight or obesity than children with narcolepsy (83% vs. 50%, p = .05). Prevalence of precocious puberty in children with narcolepsy was not higher than in control participants, but all the cases of advanced puberty involved children with narcolepsy who were diagnosed before 11 years old. All cases of central hypothyroidism belong to the narcoleptic group, who presented lower thyroid-stimulating hormone and fTA values compared to control children (respectively p = .03 and p = .001). CONCLUSIONS: No difference regarding metabolic complications was found between children with narcolepsy and control participants. Thus, metabolic disorders may be related to weight gain rather than a narcolepsy-specific risk. The presence of hypothyroidism and advanced puberty suggests a global involvement of hypothalamic structures in children with narcolepsy.

Interest of the BLAST paradigm and salivary markers for the evaluation of sleepiness in drivers.

Objectives: Sleepiness is associated with decreased cognitive abilities and remains one of the main causes of fatal road accidents. The tools currently available to assess sleepiness, such as questionnaires, are subject to intra- and inter-individual variability, while multiple sleep latency tests are only feasible in few sleep laboratories. The main objective of this study was to explore new potential markers (neurocognitive, biological) to objectively assess sleepiness in drivers. Methods: A total of 186 drivers (median age 44 years, range 20-74 years, 73% men, 14% obese) were included during a break at a highway service area, in the morning, while on the road for vacation. Questionnaires on sleepiness and sleep characteristics (habitual and on the night before travel), the Bron-Lyon Attention Stability Test (BLAST), and two salivary samples (α-amylase and oxalate) were collected. Associations between measures of sleepiness [Epworth Sleepiness Scale (ESS), and Stanford Sleepiness Scale (SSS)], sleep characteristics, neurocognitive, and biological markers were tested using regression models adjusted for confounding factors. Results: The night before travel, 83% of the drivers reduced their sleep time and 30% slept 5 h or less. The higher the number of miles to be traveled, the higher the decrease, and the shorter the sleep time. The night before travel, 18 and 24% of the drivers complained of poor sleep quality and difficulty falling asleep. The sleep characteristics on the night before travel were associated with the habitual sleep characteristics. At the time of the test, 47% of the drivers scored pathologically on the SSS. Poor sleep quality and difficulty falling asleep the night before travel were associated with increased sleepiness as assessed by the SSS and decreased attentional ability as assessed by the BLAST. No association between salivary markers and acute sleepiness was observed. Conclusions: The sleep characteristics of the night before travel were associated with sleepiness and attentional performance. The SSS and the BLAST could be used by individual drivers in a self-evaluation context. Biological markers showed a high variability and limited association with sleep parameters across subjects, emphasizing the need for within-subject designs to assess their usefulness.

Sleep and Psychosocial Characteristics of Children with Narcolepsy According to Their Intellectual Profile: A Case-Control Study.

Adequate intellectual abilities are a protective factor for psychosocial adjustments in chronic disorders. The main objective of this study was to assess the cognitive abilities, sleep, and psychosocial characteristics of children with narcolepsy compared to controls, according to their intellectual profile. Children underwent a polysomnography, completed an intellectual ability assessment, and filled out standardized questionnaires. The group with an intelligence quotient (IQ) in the area of high intellectual potential (high IQ, HIQ) consisted of 25 children with narcolepsy (HIQ-N, 40% boys, median age 11.5 years, 48% with obesity, 60% under treatment) and 25 controls (HIQ-C, 68% boys, median age 11.7 years). Compared to HIQ-C, HIQ-N had a lower perceptual reasoning index and fewer conduct disorders. The group with an IQ in the normal range (NIQ) consisted of 22 children with narcolepsy (NIQ-N, 55% boys, median age 12.1 years, 59% with obesity, 64% under treatment) and 21 controls (NIQ-C, 68% boys, median age 10 years). NIQ-N presented the same intellectual profile as NIQ-C but reported more school difficulties. In children with HIQ, those with narcolepsy appear to have a different cognitive profile than controls. NIQ seems to predict a greater impact of narcolepsy on daily-life functioning.

Cerebrospinal Fluid Histamine Levels in Healthy Children and Potential Implication for SIDS: Observational Study in a French Tertiary Care Hospital.

Objective: A defect of the waking systems could constitute a factor of vulnerability for sudden infant death syndrome (SIDS). A decrease in orexin levels, which promotes wakefulness and activates histaminergic neurons (another hypothalamic wake-promoting system) has already been demonstrated between 2 and 6 months. This work aims to study the levels of histamine (HA), tele-methylhistamine (t-MeHA), its direct metabolite, and t-MeHA/HA ratio in the cerebrospinal fluid (CSF) of healthy children, to evaluate the maturation of the histaminergic system and its possible involvement in SIDS. Methods: Seventy Eight French children between 0 and 20 years (48.7% boys) were included, all of whom had a clinical indication for lumbar puncture, but subsequently found to be normal. Measurements of HA and t-MeHA in CSF were performed by reverse phase liquid chromatography coupled to mass spectrometry detection. Statistical analyses were performed using Spearman correlations and Non-parametric pairwise ranking tests. Results: A negative correlation was found between age and CSF HA (r = -0.44, p < 10-4) and t-MeHA (r = -0.70, p < 10-4) levels. In pairwise comparisons, no difference in CSF HA and t-MeHA levels was observed between youngest age groups (i.e., 0-2 mo vs. 3-6 mo), but CSF HA and t-MeHA levels were significantly lower in older children (i.e., >6 mo vs. 0-6 mo). The CSF HA decrease with age was only observed in boys, who also presented global lower CSF HA levels than girls. Conclusion: CSF HA and t-MeHA levels decrease with age in boys, and global levels are lower in boys than in girls. These results reveal changes in histaminergic transmission and metabolism during maturation. Whether lower CSF histamine values in boys compared to girls could contribute to their higher risk of SIDS warrants further research.

Characterization of rapid weight gain phenotype in children with narcolepsy.

OBJECTIVES: To characterize the rapid weight gain (RWG) phenotype associated with the onset of childhood narcolepsy and to determine whether it could constitute a marker of severity of the disease. METHODS: RWG was defined using the BMI z-score slope reported to one year (>0.67 SD) from symptom onset to disease diagnosis. We compared the clinical, metabolic, and sleep characteristics between patients with or without RWG at diagnosis. Pharmacological management, anthropometric, and clinical progression were also evaluated during the follow-up. RESULTS: A total of 84 de novo narcoleptic pediatric patients were included; their median age at diagnosis was 12.0 years; 59.5% boys, 90.5% cataplexy, and 98.7% HLA-DQB1*06:02, 57% had RWG profile. RWG patients were younger at diagnosis than non-RWG patients, despite a shorter diagnostic delay. They had a higher BMI z-score and a higher prevalence of obesity at diagnosis, but not at symptom onset, and higher adapted Epworth Sleepiness Scale and Insomnia Severity Index scores than non-RWG patients. No differences on nocturnal polysomnography and multiple sleep latency tests were found between groups at disease diagnosis. After a median follow-up of 5 years, RWG patients still had a higher BMI z-score and a higher prevalence of obesity despite benefiting from the same therapeutic management and displaying improvement in sleepiness and school difficulties. CONCLUSIONS: Narcoleptic RWG patients were younger, sleepier, and the prevalence of obesity was higher at diagnosis despite a shorter diagnostic delay than that of non-RWG patients. These patients had also a higher risk of developing a long-term obesity, despite a positive progression of their narcoleptic symptoms. RGW could then represent a maker of a more severe phenotype of childhood narcolepsy, which should inspire a prompt and more offensive management to prevent obesity and its complications.

Maturation of Arousals during Day and Night in Preterm Infants.

The objective of this study was to compare the maturation of spontaneous arousals during day and night sleep in preterm and term infants. From the Autonomic Baby Evaluation study, the sleep and arousal characteristics of 12 preterm (35.1 ± 2.1 weeks' gestational age, GA) and 21 term (39.8 ± 0.8 weeks GA) newborns were compared between diurnal and nocturnal sleep periods at birth (M0) and 6 months (M6) of age. Models were adjusted for time (night/day), maturation (M0/M6), prematurity (yes/no). We found that preterm infants had less active sleep (AS)% than term infants with maturation during both day and night sleep, which may reflect accelerated brain maturation secondary to stress or environmental exposure after birth. Moreover, there was a difference in arousal maturation during day and night sleep in the preterm infants, as shown previously for term infants, which suggests the emergence of a circadian rhythm during the earliest postnatal period. We also showed that compared to term infants, these moderate preterm infants had fewer total arousals and, more specifically, fewer arousals in AS during day and night sleep, exposing them to a higher risk of sudden infant death syndrome.

Protocol of controlled odorant stimulation for reducing apnoeic episodes in premature newborns: a randomised open-label Latin-square study with independent evaluation of the main endpoint (PREMODEUR).

INTRODUCTION: Apnoea affects 85% of premature infants under 34 weeks of age and would be an important risk factor for subsequent neuropsychological disorders. Currently, premature children with life-threatening apnoeas receive stimulants such as methylxanthines (mainly, caffeine) or doxapram (an analeptic unlicensed in children under 15). However, these products have undesirable effects (hyperarousal, irritability, sleep disorders, tachycardia) and are not always effective because apnoea does persist in some premature newborns. Previous studies have indicated that odorant stimulation, a non-invasive intervention, may stimulate the respiratory rhythm. The objective of the present protocol is to reduce the occurrence of apnoeic episodes in premature newborns by controlled odorant stimulation added to current pharmacological treatments. METHODS AND ANALYSIS: The project is a randomised open-label Latin-square trial with independent evaluation of the main endpoint. It will include 60 preterm neonates from two university hospital neonatal intensive care units over 2 years (2021-2023). Each newborn will receive no (S0), sham (S1) or real olfactory stimulation (S2) in random order. During S2, three distinct odorants (mint, grapefruit and vanilla) will be delivered successively, in puffs, over 24 hours. Mint and grapefruit odours stimulate the main and the trigeminal olfactory pathways, whereas vanilla odour stimulates only the main olfactory pathway. A statistical analysis will compare the incidence of apnoeic episodes during S1 versus S2 using a mixed effects Poisson model. ETHICS AND DISSEMINATION: Ethical approval was obtained from the Comité de Protection des Personnes Île-de-France XI (# 2017-AO13-50-53). The results will be disseminated through various scientific meetings, specialised peer-reviewed journals and, whenever possible, posted on appropriate public websites. TRIAL REGISTRATION NUMBER: NCT02851979; Pre-results.

Intellectual Abilities of Children with Narcolepsy.

High cognitive functioning could be a protective factor for school difficulties, behavioral and mood impairments in children with narcolepsy. To investigate this factor, we studied the intellectual abilities of 74 children with narcolepsy (43 boys, 11.7 years old at diagnosis, 91% of cataplexies, 64% obese, 100% HLA positive for DR-DQB1*06:02). All children underwent a one-night polysomnography followed by Multiple Sleep Latency Tests, an evaluation of intelligence quotient (IQ), and filled standardized questionnaires. Thirty-eight percent had high potentialities (HP defined by IQ > 130) and 48% had school difficulties. Using non-parametric tests, we found that HP children reported less difficulties at school and tended to have less impulsivity, conduct, and learning disorders than those without HP. They also tended to be less obese and had less desaturation. Using a multivariate regression analysis, we found an association between the REM sleep percentage and the IQ. REM sleep could be involved in the dynamic changes contributing to the equilibrium of intellectual functioning. This study highlights that despite their frequent school difficulties, narcolepsy per se is unlikely to be a cause of intellectual disability in children. Prompt diagnosis and management of comorbidities such as obesity and obstructive sleep apnea (OSA) could improve cognitive and school performances in these children.

Sleep of Children with High Potentialities: A Polysomnographic Study.

The involvement of sleep in cognitive functioning is well known, but only a few studies have examined objective sleep parameters in children with high intellectual potential (HP). The main objective of this study was to compare sleep characteristics of 33 children with high intellectual potentialities (HP) (median 10 years old, 64% of boys) compared to 25 controls (median 11 years old, 64% of boys) and assess the difference between children with a homogeneous vs. a heterogeneous intelligence quotient (IQ) (i.e., a difference ≥15 points between verbal and non-verbal IQ). All children underwent a one-night polysomnography, an evaluation of intellectual quotient (IQ) and filled standardized questionnaires. Using non-parametric tests to compare groups' characteristics, we found that children with HP had more heterogeneous IQ, more rapid eyes movement (REM) sleep and tended to have less stage 1 sleep than controls. They also had more insomnia and sleep complaints. The high amount of REM sleep in children with HP could be advantageous for learning and could partially explain their gift. This study highlights the necessity of investigating sleep disorders in children with HP during clinical routine and reinforces the hypothesis of the involvement of nocturnal sleep, and especially REM sleep, in daytime cognition and behavior.

Sleep during development: Sex and gender differences.

Sleep occupies a substantial proportion of life. Sleep modifications parallel brain development during childhood. Sex and gender differences have been reported in brain development and many clinical and psychosocial conditions. This narrative review provides insight into the differences between girls and boys in terms of brain maturation and plasticity related to sleep and sleep characteristics (physiology, sleep duration) during development.

Feasibility of parent-attended ambulatory polysomnography in children with suspected obstructive sleep apnea.

STUDY OBJECTIVES: Due to a limited number of pediatric sleep centers, the aim was to test the feasibility of ambulatory polysomnography (PSG-home) in a group of French children suspected of OSA. METHODS: Children undergoing one-night PSG-home, with the device installed at the pediatric sleep physician's office, were prospectively included. General failure was considered when PSG-home recording captured < 5 h of artifact-free sleep or when ≥ 1 channel (nasal flow, thoraco-abdominal belts, oximetry) presented artifacts > 75% of the recording time. No-OSA was defined as an obstructive apnea-hypopnia index (OAHI) < 1 event/h and respiratory-related arousals index (RAI) < 1 event/h. OSA was defined as upper airways resistance syndrome (UARS) with OAHI < 1 event/h with RAI ≥ 1 event/h, or mild OSA (OAHI ≥ 1 event/h-5 events/h), moderate OSA (OAHI ≥ 5 events/h-10 events/h), or severe OSA (OAHI ≥ 10 events/h). Parents completed a severity hierarchy score questionnaire, Conners Parent Rating Scale, and an adapted Epworth Sleepiness Scale. RESULTS: Fifty-seven children aged 3 through 16 years were included. PSG-home was technically acceptable in 46 (81%). Failure due to nasal cannula was observed in 11% (n = 6), oximetry in 7% (n = 4), and both in 2% (n = 1) of cases. No difference in feasibility was found according to age, sex, OSA severity, or comorbidities. There were 14 (25%) children categorized as no-OSA, 43 (75%) as OSA, 4 (7%) as UARS, 26 (46%) as mild, 6 (10%) as moderate, and 7 (12%) as severe OSA. Neither questionnaires nor clinical and physical examination predicted OSA diagnosis. CONCLUSIONS: When equipment is installed at the professional's office and a parent monitors the child, PSG-home is feasible and technically acceptable in children aged 3 through 16 years old. The short delay and feasibility provided by PSG-home could improve the management of children suspected of OSA.

Sleep-disordered breathing in adolescents with obesity: When does it start to affect cardiometabolic health?

BACKGROUND AND AIMS: Pediatric obesity and sleep-disordered breathing (SDB) are associated with cardiometabolic risk (CMR), but the degree of severity at which SDB affects cardiometabolic health is unknown. We assessed the relationship between the CMR and the apnea-hypopnea index (AHI), to identify a threshold of AHI from which an increase in the CMR is observed, in adolescents with obesity. We also compared the clinical, cardiometabolic and sleep characteristics between adolescents presenting a high (CMR+) and low CMR (CMR-), according to the threshold of AHI. METHODS AND RESULTS: 114 adolescents with obesity were recruited from three institutions specialized in obesity management. Sleep and SDB as assessed by polysomnography, anthropometric parameters, fat mass (FM), glucose and lipid profiles, and blood pressure (BP) were measured at admission. Continuous (MetScoreFM) and dichotomous (metabolic syndrome, MetS) CMR were determined. Associations between MetScoreFM and AHI adjusted for BMI, sex and age were assessed by multivariable analyses. Data of 82 adolescents were analyzed. Multivariable analyses enabled us to identify a threshold of AHI = 2 above which we observed a strong and significant association between CMR and AHI (Cohen's d effect-size = 0.57 [0.11; 1.02] p = 0.02). Adolescents with CMR+ exhibited higher MetScoreFM (p < 0.05), insulin resistance (p < 0.05), systolic BP (p < 0.001), sleep fragmentation (p < 0.01) and intermittent hypoxia than CMR- group (p < 0.0001). MetS was found in 90.9% of adolescents with CMR+, versus 69.4% in the CMR- group (p < 0.05). CONCLUSIONS: The identification of a threshold of AHI ≥ 2 corresponding to the cardiometabolic alterations highlights the need for the early management of SDB and obesity in adolescents, to prevent cardiometabolic diseases. CLINICAL TRIALS: NCT03466359, NCT02588469 and NCT01358773.

Early polysomnographic characteristics associated with neurocognitive development at 36 months of age.

BACKGROUND: Few studies on the relationship between sleep quantity and/or quality and cognition have been conducted among preschoolers from the healthy general population. We aimed to identify, among 3-year-old children, early polysomnography (PSG) sleep factors associated with estimated intelligence quotient (IQ) using the Weschler Preschool and Primary Scale Intelligence-III test (WPPSI-III) and its indicators: full-scale (FISQ), verbal (VIQ), and performance (PIQ) intelligence quotients. METHODS: We included full-term children from the French birth-cohort AuBE with PSG recording at term (M0) and/or six months (M6), and available WPPSI-III scores at three years. Sleep and arousal characteristics of these infants were evaluated during day and night sleep periods. Relationships between IQ scores and sleep parameters were estimated using models with the child as a repeated effect adjusted for time (night/day), maturation (M0/M6), tobacco exposure (yes/no), anxiety-depressive scores during pregnancy, maternal age, duration of breastfeeding and child's gender. RESULTS: A total of 118 PSG recordings were obtained, representing a total of 78 unique children (38 with one PSG and 40 with two PSG). No correlations were found between night and day sleep durations at M0 or M6. Mean VIQ, PIQ, and FSIQ scores were within normal ranges. In multivariate models, longer sleep duration and higher sleep efficiency during the day were negatively associated with all IQ scores. More frequent arousals during the night were associated with lower VIQ scores. CONCLUSION: Early sleep characteristics such as night sleep fragmentation or longer naps could be associated with impaired cognitive function at three years of age.

Impaired histaminergic neurotransmission in children with narcolepsy type 1.

OBJECTIVE: Narcolepsy is a sleep disorder characterized in humans by excessive daytime sleepiness and cataplexy. Greater than fifty percent of narcoleptic patients have an onset of symptoms prior to the age of 18. Current general agreement considers the loss of hypothalamic hypocretin (orexin) neurons as the direct cause of narcolepsy notably cataplexy. To assess whether brain histamine (HA) is also involved, we quantified the cerebrospinal fluid (CSF) levels of HA and tele-methylhistamine (t-MeHA), the direct metabolite of HA between children with orexin-deficient narcolepsy type 1 (NT1) and controls. METHODS: We included 24 children with NT1 (12.3 ± 3.6 years, 11 boys, 83% cataplexy, 100% HLA DQB1*06:02) and 21 control children (11.2 ± 4.2 years, 10 boys). CSF HA and t-MeHA were measured in all subjects using a highly sensitive liquid chromatographic-electrospray/tandem mass spectrometric assay. CSF hypocretin-1 values were determined in the narcoleptic patients. RESULTS: Compared with the controls, NT1 children had higher CSF HA levels (771 vs 234 pmol/L, P < 0.001), lower t-MeHA levels (879 vs 1924 pmol/L, P < 0.001), and lower t-MeHA/HA ratios (1.1 vs 8.2, P < 0.001). NT1 patients had higher BMI z-scores (2.7 ± 1.6 vs 1.0 ± 2.3, P = 0.006) and were more often obese (58% vs 29%, P = 0.05) than the controls. Multivariable analyses including age, gender, and BMI z-score showed a significant decrease in CSF HA levels when the BMI z-score increased in patients (P = 0.007) but not in the controls. No association was found between CSF HA, t-MeHA, disease duration, age at disease onset, the presence of cataplexy, lumbar puncture timing, and CSF hypocretin levels. CONCLUSIONS: Narcolepsy type 1 children had a higher CSF HA level together with a lower t-MeHA level leading to a significant decrease in the t-MeHA/HA ratios. These results suggest a decreased HA turnover and an impairment of histaminergic neurotransmission in narcoleptic children and support the use of a histaminergic therapy in the treatment against narcolepsy.