Biological, electrophysiological and neurocognitive markers of sleepiness in children with narcolepsy

Une grande part de la population fait régulièrement l’expérience d’une somnolence au cours de la journée. Chez l’enfant, cet état peut prendre la forme d’une hyperactivité, d’une labilité émotionnelle, de troubles du comportement ou de la concentration … Malgré son apparente banalité, les répercussions de la somnolence peuvent être considérables. La somnolence est évaluée via des mesures subjectives (questionnaires) et objectives (tests itératifs de latence d’endormissement). Cependant, les premières sont sensibles à la variabilité inter- et intra-individuelle et les secondes ne sont pas utilisables hors des laboratoires. L’objectif de cette thèse était de caractériser la somnolence à l’aide d’autres marqueurs (biologiques, électrophysiologiques et neurocognitifs) dans un modèle pathologique de narcolepsie pédiatrique. Les résultats montrent que la somnolence, ses causes et répercussions, peuvent être évaluées à l’aide de différents marqueurs. L’amylase salivaire permet de discriminer la narcolepsie parmi les plaintes d’hypersomnolence ; toutefois, son extrême variabilité interindividuelle n’a pas permis de valider son utilisation en conditions écologiques. L’activité thêta, le ratio thêta/beta et les performances au BLAST constituent des outils intéressants pour évaluer les répercussions attentionnelles de la somnolence. Enfin, l’analyse du profil intellectuel et de l’architecture de sommeil permettent d’identifier des facteurs de protection contre les répercussions cognitives et psychosociales de la somnolence. Ces marqueurs présentent un intérêt pour faciliter l’évaluation et le suivi de la somnolence dans différentes pathologies ou situations.Sleepiness is experienced daily by a large part of the population. In children, this condition can result in behavioral or concentration problems, hyperactivity, emotional lability, etc. Despite its apparent banality, the repercussions of sleepiness can be disastrous. Nowadays, sleepiness is assessed by subjective (questionnaires) and objective (multiple sleep latency test) measures. However, the former is sensitive to inter- and intraindividual variability and the latter is only feasible in few sleep laboratories. The objective of this thesis was to characterize sleepiness using other markers (biological, electrophysiological and neurocognitive) in a pathological model of childhood narcolepsy. The results show that sleepiness -causes and repercussions- can be assessed using different markers. Salivary amylase allows to discriminate narcolepsy among other complaints of hypersomnolence; however, its extreme variability did not allow its validation in ecological conditions. Theta activity and theta/beta ratio, as well as BLAST behavioral measures are interesting tools to assess the attentional impact of sleepiness. Finally, the analysis of intelligence profile and sleep architecture allows the identification of protective factors against the cognitive and psychosocial repercussions of sleepiness. These markers are of interest to facilitate the evaluation and monitoring of sleepiness in various pathologies or situations

Marqueurs biologiques, électrophysiologiques et neurocognitifs de la somnolence chez l’enfant narcoleptique

Sleepiness is experienced daily by a large part of the population. In children, this condition can result in behavioral or concentration problems, hyperactivity, emotional lability, etc. Despite its apparent banality, the repercussions of sleepiness can be disastrous. Nowadays, sleepiness is assessed by subjective (questionnaires) and objective (multiple sleep latency test) measures. However, the former is sensitive to inter- and intraindividual variability and the latter is only feasible in few sleep laboratories. The objective of this thesis was to characterize sleepiness using other markers (biological, electrophysiological and neurocognitive) in a pathological model of childhood narcolepsy. The results show that sleepiness -causes and repercussions- can be assessed using different markers. Salivary amylase allows to discriminate narcolepsy among other complaints of hypersomnolence; however, its extreme variability did not allow its validation in ecological conditions. Theta activity and theta/beta ratio, as well as BLAST behavioral measures are interesting tools to assess the attentional impact of sleepiness. Finally, the analysis of intelligence profile and sleep architecture allows the identification of protective factors against the cognitive and psychosocial repercussions of sleepiness. These markers are of interest to facilitate the evaluation and monitoring of sleepiness in various pathologies or situations.Une grande part de la population fait régulièrement l’expérience d’une somnolence au cours de la journée. Chez l’enfant, cet état peut prendre la forme d’une hyperactivité, d’une labilité émotionnelle, de troubles du comportement ou de la concentration … Malgré son apparente banalité, les répercussions de la somnolence peuvent être considérables. La somnolence est évaluée via des mesures subjectives (questionnaires) et objectives (tests itératifs de latence d’endormissement). Cependant, les premières sont sensibles à la variabilité inter- et intra-individuelle et les secondes ne sont pas utilisables hors des laboratoires. L’objectif de cette thèse était de caractériser la somnolence à l’aide d’autres marqueurs (biologiques, électrophysiologiques et neurocognitifs) dans un modèle pathologique de narcolepsie pédiatrique. Les résultats montrent que la somnolence, ses causes et répercussions, peuvent être évaluées à l’aide de différents marqueurs. L’amylase salivaire permet de discriminer la narcolepsie parmi les plaintes d’hypersomnolence ; toutefois, son extrême variabilité interindividuelle n’a pas permis de valider son utilisation en conditions écologiques. L’activité thêta, le ratio thêta/beta et les performances au BLAST constituent des outils intéressants pour évaluer les répercussions attentionnelles de la somnolence. Enfin, l’analyse du profil intellectuel et de l’architecture de sommeil permettent d’identifier des facteurs de protection contre les répercussions cognitives et psychosociales de la somnolence. Ces marqueurs présentent un intérêt pour faciliter l’évaluation et le suivi de la somnolence dans différentes pathologies ou situations

Marqueurs biologiques, électrophysiologiques et neurocognitifs de la somnolence chez l’enfant narcoleptique

Sleepiness is experienced daily by a large part of the population. In children, this condition can result in behavioral or concentration problems, hyperactivity, emotional lability, etc. Despite its apparent banality, the repercussions of sleepiness can be disastrous. Nowadays, sleepiness is assessed by subjective (questionnaires) and objective (multiple sleep latency test) measures. However, the former is sensitive to inter- and intraindividual variability and the latter is only feasible in few sleep laboratories. The objective of this thesis was to characterize sleepiness using other markers (biological, electrophysiological and neurocognitive) in a pathological model of childhood narcolepsy. The results show that sleepiness -causes and repercussions- can be assessed using different markers. Salivary amylase allows to discriminate narcolepsy among other complaints of hypersomnolence; however, its extreme variability did not allow its validation in ecological conditions. Theta activity and theta/beta ratio, as well as BLAST behavioral measures are interesting tools to assess the attentional impact of sleepiness. Finally, the analysis of intelligence profile and sleep architecture allows the identification of protective factors against the cognitive and psychosocial repercussions of sleepiness. These markers are of interest to facilitate the evaluation and monitoring of sleepiness in various pathologies or situations.Une grande part de la population fait régulièrement l’expérience d’une somnolence au cours de la journée. Chez l’enfant, cet état peut prendre la forme d’une hyperactivité, d’une labilité émotionnelle, de troubles du comportement ou de la concentration … Malgré son apparente banalité, les répercussions de la somnolence peuvent être considérables. La somnolence est évaluée via des mesures subjectives (questionnaires) et objectives (tests itératifs de latence d’endormissement). Cependant, les premières sont sensibles à la variabilité inter- et intra-individuelle et les secondes ne sont pas utilisables hors des laboratoires. L’objectif de cette thèse était de caractériser la somnolence à l’aide d’autres marqueurs (biologiques, électrophysiologiques et neurocognitifs) dans un modèle pathologique de narcolepsie pédiatrique. Les résultats montrent que la somnolence, ses causes et répercussions, peuvent être évaluées à l’aide de différents marqueurs. L’amylase salivaire permet de discriminer la narcolepsie parmi les plaintes d’hypersomnolence ; toutefois, son extrême variabilité interindividuelle n’a pas permis de valider son utilisation en conditions écologiques. L’activité thêta, le ratio thêta/beta et les performances au BLAST constituent des outils intéressants pour évaluer les répercussions attentionnelles de la somnolence. Enfin, l’analyse du profil intellectuel et de l’architecture de sommeil permettent d’identifier des facteurs de protection contre les répercussions cognitives et psychosociales de la somnolence. Ces marqueurs présentent un intérêt pour faciliter l’évaluation et le suivi de la somnolence dans différentes pathologies ou situations

Maturation of Arousals during Day and Night in Preterm Infants

International audienceThe 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

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

International audienceObjectives: 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 of Children with High Potentialities: A Polysomnographic Study

International audienceThe 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 and Psychosocial Characteristics of Children with Narcolepsy According to Their Intellectual Profile: A Case–Control Study

International audienceAdequate 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

Intellectual Abilities of Children with Narcolepsy

International audienceHigh 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

Narcolepsy with cataplexy: Does age at diagnosis change the clinical picture?

International audienceObjective: To compare symptoms and sleep characteristics in patients diagnosed with narcolepsy-cataplexy (NC) before and after the age of 18 years.Methods: De novo patients with NC diagnosis completed a standardized questionnaire and interview, followed by a sleep study. The clinical and sleep measures were compared between patients diagnosed before (46 children, median age: 12 year old) and after (46 adults, median age: 28.5 year old) 18 years of age.Results: The frequency of obesity (54% vs 17%), night eating (29% vs 7%), parasomnia (89% vs 43%), sleep talking (80% vs 34%), and sleep drunkenness (69% vs 24%) were higher in children than in adults, the frequency of sleep paralysis was lower (20% vs 55%) but the frequency of cataplexy and the severity of sleepiness were not different. Children scored higher than adults at the attention-deficit/hyperactivity disorder (ADHD) scale. Depressive feelings affected not differently children (24%) and adults (32%). However, adults had lower quality of life than children. There was no difference between groups for insomnia and fatigue scores. Quality of life was essentially impacted by depressive feelings in both children and adults. Obstructive apnea-hypopnea index (OAHI) was lower in children with higher mean and minimal oxygen saturation than in adults. No between-group differences were found at the multiple sleep latency test. The body mass index (z-score) was correlated with OAHI (r = .32).Conclusion: At time of NC diagnosis, children have more frequent obesity, night eating, parasomnia, sleep talking, drunkenness, and ADHD symptoms than adults, even if sleepiness and cataplexy do not differ. These differences should be considered to ensure a prompt diagnosis

Troubles de l’attention et impact des anomalies électroencéphalographiques paroxystiques intercritiques dans les épilepsies de l’enfant : présentation d’un nouveau test d’attention soutenue synchronisé à l’EEG

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