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Sleepiness in Children
S l e e p i n e s s i n C h i l d ren An Update Gustavo Antonio Moreira, MD, PhDa,b,*, Marcia Pradella-Hallinan, MD, PhDa KEYWORDS Sleepiness Daytime somnolence Children Narcolepsy Obstructive sleep apnea Sleep deprivation
KEY POINTS Sleepiness in children has increased in the last decades as a consequences of sleep habits changes and diminished sleep duration. Chronic pain, movement disorder, and sleep-disordered breathing in children impair sleep quality and predispose to daytime sleepiness. Many questionnaire have been validated to evaluate sleep problems in children and are an important tools to evaluate subjective sleepiness. Children with central hypersomnia or circadian rhythm disorders have significant daytime problems and impairment of daytime functioning.
PREVALENCE OF SLEEPINESS IN CHILDREN A survey of 1413 Swedish children aged 6 to 11 years highlighted a prevalence of 4% prevalence
rate of daytime sleepiness. In this age group, there were no differences between boys and girls. A Korean study validated the School Sleep Habits Survey for a sample of 1457 schoolchildren aged 9 to 19 years. They found that 6.6% of the respondents admitted to daytime sleepiness being a major problem. As grade levels increased from the 5th to 12th grade, so did the prevalence of daytime sleepiness. Sleep duration decreased by approximately 3 hours on school nights from grades 5 to 12. The authors noted that sleepiness was slightly more prevalent in girls than boys. The increasing prevalence of daytime sleepiness with advancing grade level in children and adolescents is further corroborated by other studies.4,5 In a study of 535 Brazilian adolescents, daytime sleepiness increased from 10 to 17 years of age. Students from private schools had higher sleepiness scores than students from public schools. More than 2 hours of sleep debt, measured as the difference of the mean sleep duration between school night and weekend nights, was present in 39% of these adolescents.4
Disclosure Statement: The authors have nothing to disclose. a Department of Psychobiology, Universidade Federal de Sa˜o Paulo, Rua Napolea˜o de Barros, 925, Sa˜o Paulo, Sa˜o Paulo 04024-002, Brazil; b Department of Pediatrics, Universidade Federal de Sa˜o Paulo, Rua Botucatu, 598, Sa˜o Paulo, Sa˜o Paulo 04023-062, Brazil * Corresponding author. Rua Napolea˜o de Barros, 925, Sa˜o Paulo, Sa˜o Paulo 04024-002, Brazil. E-mail address: [email protected] Sleep Med Clin - (2017) -–http://dx.doi.org/10.1016/j.jsmc.2017.03.013 1556-407X/17/Ó 2017 Elsevier Inc. All rights reserved.
sleep.theclinics.com
Sleep is essential for children’s learning, memory processes, school performance, and general well-being.1 Sleep deprivation and fragmented sleep are the main mechanism that leads to daytime sleepiness in children.2 Evaluation of sleepiness in this age group is quite challenging owing to the age-dependent maturation of the central nervous system. As age progresses, time spent sleeping is reduced and the polyphasic sleep pattern of preschool children matures to an exclusive nocturnal monophasic sleep in older children. This may, in part, explain why the evaluation of sleepiness in children is taxing. Many tools have been developed to evaluate sleep in a pediatric age group, however, a limited number of questionnaires have been fully validated to comprehend sleepiness in children.3
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Moreira & Pradella-Hallinan EFFECTS OF SLEEP DEPRIVATION In the last few decades, the time adults, adolescents and children have spent sleeping has decreased. This change in habits is mainly owing to the overwhelming use of electricity. Currently, artificial light and electronic gadgets have invaded the lives of humans, day and night. Many studies have showed that increases in screen time have reduced the duration of sleep in children.6 It is not surprising that these reductions of sleep duration have daytime consequences, such as sleepiness, behavior problems, cognitive deficits, poor school performance, inflammation, and metabolic dysfunction.1,2,7–9 A recent systematic review demonstrated a consistent correlation of screen time with reduced sleep duration.6 The authors suggested that the reduction in sleep time can be associated with biological, psychological, and environmental factors. The 2013 International Sleep Poll reported that 7% to 21% of adults in the United States, Germany, the United Kingdom, Canada, Mexico, and Japan sleep fewer than 6 hours per night on work days.10 The 2011 Sleep in America Poll reported that about 60% of adolescents in the United States receive less than 8 hours of sleep on school nights. In the same report, 90% of 13 to 18 years olds had at least 1 electronic device (TV, laptop, cell phone, tablet, video game, and/or music player) in their bedroom.11 With the ubiquitous presence of media items in a child’s or an adolescent’s bedroom, screen time is hypothesized to be a cause of insufficient and low-quality sleep, operating through several mechanisms. The first is time displacement. With more time spent in front of screens, less time is naturally available for sleep. Second, psychological and physiologic arousals owing to the content of the media and social interaction may also interfere with the ability to fall and stay asleep. Finally, there is the effect of light on both circadian rhythm and general alertness. The effect in the circadian rhythm is mainly owing to light suppression of melatonin secretion.6 Recent reviews have shown that sleep quantity and quality in children correlates with levels of daytime sleepiness.12–14 Sleep quality and sleep duration may be seen as 2 separate sleep domains. Although these sleep domains overlap to some extent, qualitative differences do exist between them. Sleep quality refers to the subjective indices of how sleep is experienced, including the feeling of feeling rested when waking up and experiencing satisfaction with sleep. Sleep duration, on the other hand, is a more objective sleep domain, namely, the actual time during which the individual is asleep. Correlations between children and adolescents’ sleep duration and sleep quality
are low or not significant, supporting the idea that sleep quality and sleep duration represent 2 separate sleep domains. In fact, the strength of association of sleep quantity and sleep duration with sleepiness may vary by student age and sex; 1 recent metaanalysis of sleep and school functioning reported that studies of younger children, particularly those that enrolled more boys, tended to show the greatest effects.14 Poor sleep quality owing to pain,15 periodic limb movement,16 and sleep-disordered breathing17 may also lead to sleepiness in children.18 Obstructive sleep apnea (OSA) is a sleep disorder characterized by repetitive upper airway obstruction during sleep, leading to hypoxemia, hypercapnia, fragmented sleep, and daytime symptoms.17 Although daytime somnolence in children with OSA is not as significant as when seen in adults,19 studies have shown that OSA in children aged 5 to 12 years has been linked to poor classroom grades, sleepiness, inattention, hyperactivity, oppositional behavior, and mood deregulation.20 Further evidence that links pediatric OSA and sleepiness is the fact that treatment with adenotonsillectomy21,22 or positive airway pressure23 improves daytime behavior, sleepiness, and quality of life. Restless leg syndrome and period limb movements disorder may also lead to sleep fragmentation and, consequently, daytime dysfunction. Cross-sectional studies have shown associations of restless leg syndrome and period limb movements disorder with hyperactivity, impulsivity, attention, and daytime sleepiness.16,24,25 Currently, there is no evidence that intervention for movement disorders in children may improve these symptoms.
ASSESSMENT OF SLEEPINESS There are a few tools for the assessment of sleep duration and sleepiness in children. Approximately 57 pediatric sleep questionnaires were developed to evaluate sleep problems in children and/or adolescents. Only a few underwent a thorough validation process.3 The questionnaires evaluate sleep environment and settling down periods, sleep behavior, sleep habits, circadian typology, emotional well-being, scholastic achievement, and sleepiness. Assessment of sleepiness represented whole or part of the questionnaires (Table 1). These tools look to age differences in sleep patterns, split into infants, preschoolers, school-age children, and adolescents. The age range varies from 2 to 18 years, although most of them focus on adolescents. The Epworth Sleepiness Scale, a well-known scale used in adults, was modified in 2 items to be more applicable to
Sleepiness in Children
Table 1 Subjective tools for evaluation sleepiness in children and adolescents
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Bruni et al, 1996 Chervin et al,28 2000 Luginbuehl et al,27 2008 Luginbuehl et al,27 2008 Melendres et al,18 2004 Spilsbury et al,29 2007 Drake et al,13 2003
Scale
Age Range (y)
Questions Concerning Sleepiness
Sleep Disturbances Scale for Children Pediatric Sleep Questionnaire Sleep Disorder Inventory for Children (child version) Sleep Disorder Inventory for Children (adolescent version) Modified Epworth Sleepiness Scale Cleveland Adolescent Sleepiness Questionnaire Pediatric Daytime Sleepiness Scale
6.5–15.3 2–18 2–10
5/26 4/22 3/25
11–18
5/25
2–16 11–17
8/8 16/16
11–15
8/8
children. Although the modified Epworth Sleepiness Scale scores were statistically higher in children with OSA than in controls, the scale fails to demonstrate differences between patients with primary snoring and OSA.18 The Pediatric Daytime Sleepiness Scale is a self-report scale developed for children and adolescents aged 11 to 18 years. Eight questions on a 5-step Likert scale were selected from an initial 32 questions, based on factor analysis and internal consistency. Pediatric daytime sleepiness scores was higher in children and adolescents who reported low school achievement, high rates of absenteeism, low school enjoyment, low total sleep time, and frequent illness.13 Three well-validated and common questionnaires for sleep problems in a wide pediatric age range highlighted many aspects of sleep problems, and some of these questions evaluate sleepiness.26–28 The Pediatric Sleep Questionnaire and the Modified Epworth Sleepiness Scale had recently shown, in a randomized, controlled trial, statistically significant improvement in sleepiness scores after adenotonsillectomy.30 Objective evaluation of sleepiness using the Multiple Sleep Latency Test (MSLT) can be performed in children older than 5 years. MSLT measures the speed of falling asleep. A faster sleep onset indicates a greater level of sleepiness.31,32 During an MSLT, subjects are asked to fall asleep while lying in bed in a dark and quiet room during five 20-minute periods spaced at 2-hour intervals. If sleep occurs during this time period, it is allowed for only 15 minutes. If no sleep occurs, lights are turned on after the 20-minute test and the subject has to get out of bed and stay awake until the next testing period. A nocturnal polysomnography is recommended to rule out other sleep disorders
and ensure that the child is not sleep deprived. Prepubertal children are less likely to fall asleep during the MSLT than older adolescents, suggesting that the standard protocol may underestimate mild degrees of sleepiness.33,34 To address this concern, some researchers have modified the standard protocol by using 30-minute nap opportunities instead of 20 minutes.19,35 In children with suspected sleep-disordered breathing, they demonstrated that daytime sleepiness is associated with the degree of obesity, severity of the OSA, and tumor necrosis factor-a levels.19,35 Adenotonsillectomy improves the degree of sleepiness measured with MSLT and tumor necrosis factor-a levels.35,36 MSLT, preceded by nocturnal polysomnography, is indicated in children as a part of the evaluation for suspected narcolepsy. The American Academy of Sleep Medicine stated that there is sufficient evidence to use MSLT diagnose narcolepsy in children older than 5 years, and report it as a standard recommendation.32 Additional studies when daytime sleepiness and decrease of alertness in children or adolescents become a serious concern are recommended. Below, we refer to the more frequently discussed conditions associated with daytime sleepiness for these age groups.
NARCOLEPSY Narcolepsy is a disorder of central origin characterized by recurrent attacks of irresistible daytime sleepiness. The characteristic picture of narcolepsy encompasses a tetrad of symptoms that includes excessive daytime sleepiness, sleep paralysis, hypnagogic/hypnopompic hallucinations, and cataplexy; fragmented nocturnal sleep tends also to occur. The prevalence of narcolepsy is
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Moreira & Pradella-Hallinan 0.02% in the world general population. About 30% of narcoleptic patients exhibit its initial symptoms during childhood and in 16% of these cases, narcolepsy begins before the age of 10 years. Narcolepsy is probably underestimated because of the high rate of misdiagnosis. The incidence is approximately 1.37 per 100,000 personyears.37–40 The disease affects both males and females and the etiopathogenesis remains unknown. Recently, the involvements of the hypocretin-1 and hypocretin-2 pathways have shed new light on the disorder. These neurotransmitters produce exclusively from the lateral hypothalamus, playing a major role in wakefulness and REM sleep physiology.37,39 The revised International Classification of Sleep Disorders, 3rd edition (ICSD-3) divides the disease into narcolepsy type 1 (N1), which is characterized by excessive daytime sleepiness and cataplexy associated with hypocretin-1 deficiency. The close association with HLA DQB10602 haplotype together with the role of environmental triggers such as H1N1 influenza virus infection or vaccination, streptococcus b-hemolyticus infection, and low or undetectable hypocretin-1 levels in the cerebrospinal fluid support the hypothesis of an autoimmune etiology.37,38,41,42 Children with N1 may present with a peculiar cataplexy phenotype, characterized by persistent hypotonia with prominent facial involvement known as cataplectic facies and by hyperkinetic movements that occurs associated to emotional or strong stimulation by sounds, fright, or tickling. This pediatric phenotype progressively changes to the adult phenotype of cataplexy, with muscle weakness evoked by emotions. Frequently, childhood also shows behavioral abnormalities and psychiatric disorders, encompassing depressive feelings, hyperactive or aggressive behavior, and even psychotic features. The association with obesity and precocious puberty strikingly suggests that N1 arising in prepubertal children may reflect a wide hypothalamic dysfunction probably owing to hypocretin neuronal loss. Children with N1 phenotypes need specific evaluation and management, especially regarding behavioral and metabolic features. N1 is indeed a lifelong disorder with a devastating impact on quality of life, especially when arising at a developmental age. Targeted school programs, and juridical and psychological supports are all essential for patients and families.38,39 Diagnostic criteria are based on clinical, nocturnal polysomnography, and MSLT findings that are specific for children.43 Narcolepsy type 2 is characterized by excessive daytime sleepiness without cataplexy and hypocretin deficiency, and
is diagnosed based on patients’ complaints and polysomnographic evidence in the absence of other causes of daytime sleepiness.41 The secondary or symptomatic form of narcolepsy is owing to a medical condition. This includes brain tumors, brain trauma, some diseases such as sarcoidosis, Niemann–Pick type C, demyelinating disorders, and stroke resulting in damage to the hypocretin pathways.37–39,43
IDIOPATHIC HYPERSOMNIA WITH OR WITHOUT PROLONGED SLEEP TIME The condition is characterized by excessive daytime sleepiness that extends over several months. Nocturnal sleep may have prolonged duration (12–14 hours) or be in the normal range. Diurnal naps generally are prolonged (3–4 hours) but unrefreshing. After a sleep period, it is not infrequent that children present with confusion on awakening and sleep drunkenness, associated with automatic and complex behavior. Microsleeps (1–4 seconds) may be recorded during the day.44 The prevalence is however not well established. It may begin in the midteens and seems to be more common in women than in men. Polysomnography and MSLT recordings show short sleep latency with increased or normal total sleep time. Sleep architecture is normal but it may have an increase in NREM stage 3 in the second half of the night. Daytime sleep shows mainly NREM episodes and the latency is always less than 10 minutes.45,46 The most important consequences are poor academic performance. Treatment consists of the use of stimulants and, more recently, L-carnitine alone or in association with stimulants was introduced and seems to have beneficial effect.46,47 When off medication, children with excessive daytime sleepiness were more likely to get hit or nearly hit by traffic than a group of children matched by age, sex, race, and household income.48
RECURRENT HYPERSOMNIAS Klein-Levin Syndrome Klein-Levin syndrome is characterized by recurrent episodes of hypersomnolence that are frequently associated with hyperphagia and hypersexual behaviors. The episodes may last 1 or 2 days or several weeks and are characterized by spending an overly long time in bed (16–18 hours). During this period, the patient sometimes can get up, eat, and go to the restroom. A change in personality, behavior, and psychological mood is frequently seen and also a stuporous appearance can be noticed.49,50
Sleepiness in Children It is a rare condition, 3 times more frequent in males than females and starts during adolescence. The pathophysiology is not conclusive, but some studies highlighted diffuse brain hypoperfusion (more pronounced in the thalamic and frontotemporal areas), viral and autoimmune causative factors based on the frequent report of flulike symptoms at onset. The most frequent precipitating factor (70%) is the presence of inflammatory lesions in the thalamus, diencephalon, and midbrain on postmortem neuropathology, suggesting a viral infection, increased frequency of the human leukocyte antigen DQB1*0201 allele, and, in a few cases, abnormalities in serotonin and dopamine metabolism, suggesting a neurotransmitter imbalance in the serotonergic or dopaminergic pathway. There are also some patients who started with somnolence after a head trauma.49,50 Polysomnography and MSLT are not required for diagnostic reasons. There is no treatment consensus. Lithium may be beneficial to reduce relapses, and modafinil may reduce duration of episodes. Recently, clarithromycin was also suggested as a treatment, but the effectiveness of this drug needs to be studied in more patients.51
Menstrual-Related Hypersomnia There is an association of hypersomnolence periods with menstruation. Patients experienced longer sleep nocturnal duration and daytime sleepiness. Polysomnography shows shortened sleep latency and normal architecture. A good response with anovulatory agents reinforces the suspicion of a hormonal origin of the condition.52,53
Hypersomnia Associated with Behaviorally Induced Insufficient Sleep Sleep deprivation in children and adolescents is considered a health concern. In the last century, children decreased sleep duration and now they are sleeping about 1 hour less compared with 100 years ago.11,54 Studies with sleep deprivation have shown the importance and necessity of having adequate sleep quality and duration.2 For children, it is believed, and easily seen in clinical practice, that sleep influences physical growth, emotional stability, behavior, and cognitive function, including memory consolidation. Studies have shown that insufficient sleep is associated with fatigue, attention problems, learning difficulties, impulse control, and organizational skills poverty. In children and adolescents, short sleep is associated with overweight and obesity, higher caloric intake derived from fat and lower caloric intake from carbohydrates, and insulin resistance.55,56
The medical literature from the last 50 years shows that concepts of modernity have been associated with overstimulation that predisposes children not getting the sleep that they need. Recently, the influence of electronic media including video games, cell phones, and the Internet were implicated in increased night-time activity and affected sleep patterns of not only in adults, but also in children and adolescents. Strategies to reduce sleep deprivation are necessary to prevent damages during developmental ages and to promote a better quality of sleep for all.4,55,56
Hypersomnia Associated with Circadian Rhythm Disorder Delayed sleep phase syndrome is a circadian rhythm disorder characterized by a constitutional inability to anticipate sleep and a tendency to fall asleep at progressively later times at night. Because sleep-onset time is often as late as 1 to 3 AM, children and adolescents with this disorder are often sleep deprived on school nights and are consequently sleepy during the daytime.57 Although delayed sleep phase syndrome has its peak incidence during adolescence, many children already have symptoms in prepubertal years. If allowed to sleep uninterrupted, as happens on weekends or holidays, the individual may sleep until noon and feel refreshed. There is no qualitative or quantitative abnormality in sleep. Sleep onset and offset are simply at socially inappropriate times and lead to daytime sleepiness when the patient has to conform to the societal norms for attending school or work. Complaints of difficulty of sleeping early at night are viewed as insomnia. In the morning, patients manifest chronic hypersomnia. Being late or absent to school becomes a serious problem. Delayed sleep phase syndrome is related to a dysfunction of the suprachiasmatic nucleus, which is our circadian timekeeper. Patients show a delay in the timing of release of melatonin (a sleep-inducing hormone), and in reaching the nadir of the core body temperature, which corresponds with the time that a person is likely to be most sleepy.58 Delayed sleep phase syndrome may be associated with certain polymorphisms in the PER3 circadian gene.59 Treatment consists of keeping a rigid morning wake up time 7 days a week, early exposure to bright sunlight for 30 minutes immediately on awakening in the morning, and oral melatonin before the desired bedtime.60
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47. Miyagawa T, Kawamura H, Obuchi M, et al. Effects of oral L-carnitine administration in narcolepsy patients: a randomized, double-blind, cross-over and placebo-controlled trial. PLoS One 2013;8(1): e53707. 48. Avis KT, Gamble KL, Schwebel DC. Does excessive daytime sleepiness affect children’s pedestrian safety? Sleep 2014;37(2):283–7. 49. Arnulf I, Zeitzer JM, File J, et al. Kleine-Levin syndrome: a systematic review of 186 cases in the literature. Brain 2005;128(Pt 12):2763–76. 50. Ramdurg S. Kleine-Levin syndrome: etiology, diagnosis, and treatment. Ann Indian Acad Neurol 2010;13(4):241–6. 51. Rezvanian E, Watson NF. Kleine-Levin syndrome treated with clarithromycin. J Clin Sleep Med 2013; 9(11):1211–2. 52. Sagale´s T. Outras hipersonias. In: Paiva T, Andersen ML, Tufik S, editors. O Sono e a Medicina do Sono. 1st edition. Barueri (Brazil): Editora Manole; 2014. p. 340–5. 53. Baker F. Menstrual-related hypersomnia. In: Thorpy MJ, Billiard M, editors. Sleepiness: causes, consequences and treatment. Cambridge (United Kingdom): Cambridge University Press; 2011. p. 147–9. 54. Paruthi S, Brooks LJ, D’Ambrosio C, et al. Consensus statement of the American Academy of sleep medicine on the recommended amount of sleep for healthy children: methodology and discussion. J Clin Sleep Med 2016;12(11):1549–61. 55. Pereira EF, Barbosa DG, Andrade RD, et al. Sleep and adolescence: how many hours sleep teenagers need? J Bras Psiquiatr 2015;64(1):40–4. 56. Matricciani LA, Olds TS, Blunden S, et al. Never enough sleep: a brief history of sleep recommendations for children. Pediatrics 2012; 129(3):548–56. 57. Garcia J, Rosen G, Mahowald M. Circadian rhythms and circadian rhythm disorders in children and adolescents. Semin Pediatr Neurol 2001;8(4):229–40. 58. Crowley SJ, Acebo C, Carskadon MA. Sleep, circadian rhythms, and delayed phase in adolescence. Sleep Med 2007;8(6):602–12. 59. Archer SN, Robilliard DL, Skene DJ, et al. A length polymorphism in the circadian clock gene Per3 is linked to delayed sleep phase syndrome and extreme diurnal preference. Sleep 2003;26(4): 413–5. 60. Mundey K, Benloucif S, Harsanyi K, et al. Phasedependent treatment of delayed sleep phase syndrome with melatonin. Sleep 2005;28(10):1271–8.
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KEY POINTS Sleepiness in children has increased in the last decades as a consequences of sleep habits changes and diminished sleep duration. Chronic pain, movement disorder, and sleep-disordered breathing in children impair sleep quality and predispose to daytime sleepiness. Many questionnaire have been validated to evaluate sleep problems in children and are an important tools to evaluate subjective sleepiness. Children with central hypersomnia or circadian rhythm disorders have significant daytime problems and impairment of daytime functioning.
PREVALENCE OF SLEEPINESS IN CHILDREN A survey of 1413 Swedish children aged 6 to 11 years highlighted a prevalence of 4% prevalence
rate of daytime sleepiness. In this age group, there were no differences between boys and girls. A Korean study validated the School Sleep Habits Survey for a sample of 1457 schoolchildren aged 9 to 19 years. They found that 6.6% of the respondents admitted to daytime sleepiness being a major problem. As grade levels increased from the 5th to 12th grade, so did the prevalence of daytime sleepiness. Sleep duration decreased by approximately 3 hours on school nights from grades 5 to 12. The authors noted that sleepiness was slightly more prevalent in girls than boys. The increasing prevalence of daytime sleepiness with advancing grade level in children and adolescents is further corroborated by other studies.4,5 In a study of 535 Brazilian adolescents, daytime sleepiness increased from 10 to 17 years of age. Students from private schools had higher sleepiness scores than students from public schools. More than 2 hours of sleep debt, measured as the difference of the mean sleep duration between school night and weekend nights, was present in 39% of these adolescents.4
Disclosure Statement: The authors have nothing to disclose. a Department of Psychobiology, Universidade Federal de Sa˜o Paulo, Rua Napolea˜o de Barros, 925, Sa˜o Paulo, Sa˜o Paulo 04024-002, Brazil; b Department of Pediatrics, Universidade Federal de Sa˜o Paulo, Rua Botucatu, 598, Sa˜o Paulo, Sa˜o Paulo 04023-062, Brazil * Corresponding author. Rua Napolea˜o de Barros, 925, Sa˜o Paulo, Sa˜o Paulo 04024-002, Brazil. E-mail address: [email protected] Sleep Med Clin - (2017) -–http://dx.doi.org/10.1016/j.jsmc.2017.03.013 1556-407X/17/Ó 2017 Elsevier Inc. All rights reserved.
sleep.theclinics.com
Sleep is essential for children’s learning, memory processes, school performance, and general well-being.1 Sleep deprivation and fragmented sleep are the main mechanism that leads to daytime sleepiness in children.2 Evaluation of sleepiness in this age group is quite challenging owing to the age-dependent maturation of the central nervous system. As age progresses, time spent sleeping is reduced and the polyphasic sleep pattern of preschool children matures to an exclusive nocturnal monophasic sleep in older children. This may, in part, explain why the evaluation of sleepiness in children is taxing. Many tools have been developed to evaluate sleep in a pediatric age group, however, a limited number of questionnaires have been fully validated to comprehend sleepiness in children.3
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Moreira & Pradella-Hallinan EFFECTS OF SLEEP DEPRIVATION In the last few decades, the time adults, adolescents and children have spent sleeping has decreased. This change in habits is mainly owing to the overwhelming use of electricity. Currently, artificial light and electronic gadgets have invaded the lives of humans, day and night. Many studies have showed that increases in screen time have reduced the duration of sleep in children.6 It is not surprising that these reductions of sleep duration have daytime consequences, such as sleepiness, behavior problems, cognitive deficits, poor school performance, inflammation, and metabolic dysfunction.1,2,7–9 A recent systematic review demonstrated a consistent correlation of screen time with reduced sleep duration.6 The authors suggested that the reduction in sleep time can be associated with biological, psychological, and environmental factors. The 2013 International Sleep Poll reported that 7% to 21% of adults in the United States, Germany, the United Kingdom, Canada, Mexico, and Japan sleep fewer than 6 hours per night on work days.10 The 2011 Sleep in America Poll reported that about 60% of adolescents in the United States receive less than 8 hours of sleep on school nights. In the same report, 90% of 13 to 18 years olds had at least 1 electronic device (TV, laptop, cell phone, tablet, video game, and/or music player) in their bedroom.11 With the ubiquitous presence of media items in a child’s or an adolescent’s bedroom, screen time is hypothesized to be a cause of insufficient and low-quality sleep, operating through several mechanisms. The first is time displacement. With more time spent in front of screens, less time is naturally available for sleep. Second, psychological and physiologic arousals owing to the content of the media and social interaction may also interfere with the ability to fall and stay asleep. Finally, there is the effect of light on both circadian rhythm and general alertness. The effect in the circadian rhythm is mainly owing to light suppression of melatonin secretion.6 Recent reviews have shown that sleep quantity and quality in children correlates with levels of daytime sleepiness.12–14 Sleep quality and sleep duration may be seen as 2 separate sleep domains. Although these sleep domains overlap to some extent, qualitative differences do exist between them. Sleep quality refers to the subjective indices of how sleep is experienced, including the feeling of feeling rested when waking up and experiencing satisfaction with sleep. Sleep duration, on the other hand, is a more objective sleep domain, namely, the actual time during which the individual is asleep. Correlations between children and adolescents’ sleep duration and sleep quality
are low or not significant, supporting the idea that sleep quality and sleep duration represent 2 separate sleep domains. In fact, the strength of association of sleep quantity and sleep duration with sleepiness may vary by student age and sex; 1 recent metaanalysis of sleep and school functioning reported that studies of younger children, particularly those that enrolled more boys, tended to show the greatest effects.14 Poor sleep quality owing to pain,15 periodic limb movement,16 and sleep-disordered breathing17 may also lead to sleepiness in children.18 Obstructive sleep apnea (OSA) is a sleep disorder characterized by repetitive upper airway obstruction during sleep, leading to hypoxemia, hypercapnia, fragmented sleep, and daytime symptoms.17 Although daytime somnolence in children with OSA is not as significant as when seen in adults,19 studies have shown that OSA in children aged 5 to 12 years has been linked to poor classroom grades, sleepiness, inattention, hyperactivity, oppositional behavior, and mood deregulation.20 Further evidence that links pediatric OSA and sleepiness is the fact that treatment with adenotonsillectomy21,22 or positive airway pressure23 improves daytime behavior, sleepiness, and quality of life. Restless leg syndrome and period limb movements disorder may also lead to sleep fragmentation and, consequently, daytime dysfunction. Cross-sectional studies have shown associations of restless leg syndrome and period limb movements disorder with hyperactivity, impulsivity, attention, and daytime sleepiness.16,24,25 Currently, there is no evidence that intervention for movement disorders in children may improve these symptoms.
ASSESSMENT OF SLEEPINESS There are a few tools for the assessment of sleep duration and sleepiness in children. Approximately 57 pediatric sleep questionnaires were developed to evaluate sleep problems in children and/or adolescents. Only a few underwent a thorough validation process.3 The questionnaires evaluate sleep environment and settling down periods, sleep behavior, sleep habits, circadian typology, emotional well-being, scholastic achievement, and sleepiness. Assessment of sleepiness represented whole or part of the questionnaires (Table 1). These tools look to age differences in sleep patterns, split into infants, preschoolers, school-age children, and adolescents. The age range varies from 2 to 18 years, although most of them focus on adolescents. The Epworth Sleepiness Scale, a well-known scale used in adults, was modified in 2 items to be more applicable to
Sleepiness in Children
Table 1 Subjective tools for evaluation sleepiness in children and adolescents
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Bruni et al, 1996 Chervin et al,28 2000 Luginbuehl et al,27 2008 Luginbuehl et al,27 2008 Melendres et al,18 2004 Spilsbury et al,29 2007 Drake et al,13 2003
Scale
Age Range (y)
Questions Concerning Sleepiness
Sleep Disturbances Scale for Children Pediatric Sleep Questionnaire Sleep Disorder Inventory for Children (child version) Sleep Disorder Inventory for Children (adolescent version) Modified Epworth Sleepiness Scale Cleveland Adolescent Sleepiness Questionnaire Pediatric Daytime Sleepiness Scale
6.5–15.3 2–18 2–10
5/26 4/22 3/25
11–18
5/25
2–16 11–17
8/8 16/16
11–15
8/8
children. Although the modified Epworth Sleepiness Scale scores were statistically higher in children with OSA than in controls, the scale fails to demonstrate differences between patients with primary snoring and OSA.18 The Pediatric Daytime Sleepiness Scale is a self-report scale developed for children and adolescents aged 11 to 18 years. Eight questions on a 5-step Likert scale were selected from an initial 32 questions, based on factor analysis and internal consistency. Pediatric daytime sleepiness scores was higher in children and adolescents who reported low school achievement, high rates of absenteeism, low school enjoyment, low total sleep time, and frequent illness.13 Three well-validated and common questionnaires for sleep problems in a wide pediatric age range highlighted many aspects of sleep problems, and some of these questions evaluate sleepiness.26–28 The Pediatric Sleep Questionnaire and the Modified Epworth Sleepiness Scale had recently shown, in a randomized, controlled trial, statistically significant improvement in sleepiness scores after adenotonsillectomy.30 Objective evaluation of sleepiness using the Multiple Sleep Latency Test (MSLT) can be performed in children older than 5 years. MSLT measures the speed of falling asleep. A faster sleep onset indicates a greater level of sleepiness.31,32 During an MSLT, subjects are asked to fall asleep while lying in bed in a dark and quiet room during five 20-minute periods spaced at 2-hour intervals. If sleep occurs during this time period, it is allowed for only 15 minutes. If no sleep occurs, lights are turned on after the 20-minute test and the subject has to get out of bed and stay awake until the next testing period. A nocturnal polysomnography is recommended to rule out other sleep disorders
and ensure that the child is not sleep deprived. Prepubertal children are less likely to fall asleep during the MSLT than older adolescents, suggesting that the standard protocol may underestimate mild degrees of sleepiness.33,34 To address this concern, some researchers have modified the standard protocol by using 30-minute nap opportunities instead of 20 minutes.19,35 In children with suspected sleep-disordered breathing, they demonstrated that daytime sleepiness is associated with the degree of obesity, severity of the OSA, and tumor necrosis factor-a levels.19,35 Adenotonsillectomy improves the degree of sleepiness measured with MSLT and tumor necrosis factor-a levels.35,36 MSLT, preceded by nocturnal polysomnography, is indicated in children as a part of the evaluation for suspected narcolepsy. The American Academy of Sleep Medicine stated that there is sufficient evidence to use MSLT diagnose narcolepsy in children older than 5 years, and report it as a standard recommendation.32 Additional studies when daytime sleepiness and decrease of alertness in children or adolescents become a serious concern are recommended. Below, we refer to the more frequently discussed conditions associated with daytime sleepiness for these age groups.
NARCOLEPSY Narcolepsy is a disorder of central origin characterized by recurrent attacks of irresistible daytime sleepiness. The characteristic picture of narcolepsy encompasses a tetrad of symptoms that includes excessive daytime sleepiness, sleep paralysis, hypnagogic/hypnopompic hallucinations, and cataplexy; fragmented nocturnal sleep tends also to occur. The prevalence of narcolepsy is
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Moreira & Pradella-Hallinan 0.02% in the world general population. About 30% of narcoleptic patients exhibit its initial symptoms during childhood and in 16% of these cases, narcolepsy begins before the age of 10 years. Narcolepsy is probably underestimated because of the high rate of misdiagnosis. The incidence is approximately 1.37 per 100,000 personyears.37–40 The disease affects both males and females and the etiopathogenesis remains unknown. Recently, the involvements of the hypocretin-1 and hypocretin-2 pathways have shed new light on the disorder. These neurotransmitters produce exclusively from the lateral hypothalamus, playing a major role in wakefulness and REM sleep physiology.37,39 The revised International Classification of Sleep Disorders, 3rd edition (ICSD-3) divides the disease into narcolepsy type 1 (N1), which is characterized by excessive daytime sleepiness and cataplexy associated with hypocretin-1 deficiency. The close association with HLA DQB10602 haplotype together with the role of environmental triggers such as H1N1 influenza virus infection or vaccination, streptococcus b-hemolyticus infection, and low or undetectable hypocretin-1 levels in the cerebrospinal fluid support the hypothesis of an autoimmune etiology.37,38,41,42 Children with N1 may present with a peculiar cataplexy phenotype, characterized by persistent hypotonia with prominent facial involvement known as cataplectic facies and by hyperkinetic movements that occurs associated to emotional or strong stimulation by sounds, fright, or tickling. This pediatric phenotype progressively changes to the adult phenotype of cataplexy, with muscle weakness evoked by emotions. Frequently, childhood also shows behavioral abnormalities and psychiatric disorders, encompassing depressive feelings, hyperactive or aggressive behavior, and even psychotic features. The association with obesity and precocious puberty strikingly suggests that N1 arising in prepubertal children may reflect a wide hypothalamic dysfunction probably owing to hypocretin neuronal loss. Children with N1 phenotypes need specific evaluation and management, especially regarding behavioral and metabolic features. N1 is indeed a lifelong disorder with a devastating impact on quality of life, especially when arising at a developmental age. Targeted school programs, and juridical and psychological supports are all essential for patients and families.38,39 Diagnostic criteria are based on clinical, nocturnal polysomnography, and MSLT findings that are specific for children.43 Narcolepsy type 2 is characterized by excessive daytime sleepiness without cataplexy and hypocretin deficiency, and
is diagnosed based on patients’ complaints and polysomnographic evidence in the absence of other causes of daytime sleepiness.41 The secondary or symptomatic form of narcolepsy is owing to a medical condition. This includes brain tumors, brain trauma, some diseases such as sarcoidosis, Niemann–Pick type C, demyelinating disorders, and stroke resulting in damage to the hypocretin pathways.37–39,43
IDIOPATHIC HYPERSOMNIA WITH OR WITHOUT PROLONGED SLEEP TIME The condition is characterized by excessive daytime sleepiness that extends over several months. Nocturnal sleep may have prolonged duration (12–14 hours) or be in the normal range. Diurnal naps generally are prolonged (3–4 hours) but unrefreshing. After a sleep period, it is not infrequent that children present with confusion on awakening and sleep drunkenness, associated with automatic and complex behavior. Microsleeps (1–4 seconds) may be recorded during the day.44 The prevalence is however not well established. It may begin in the midteens and seems to be more common in women than in men. Polysomnography and MSLT recordings show short sleep latency with increased or normal total sleep time. Sleep architecture is normal but it may have an increase in NREM stage 3 in the second half of the night. Daytime sleep shows mainly NREM episodes and the latency is always less than 10 minutes.45,46 The most important consequences are poor academic performance. Treatment consists of the use of stimulants and, more recently, L-carnitine alone or in association with stimulants was introduced and seems to have beneficial effect.46,47 When off medication, children with excessive daytime sleepiness were more likely to get hit or nearly hit by traffic than a group of children matched by age, sex, race, and household income.48
RECURRENT HYPERSOMNIAS Klein-Levin Syndrome Klein-Levin syndrome is characterized by recurrent episodes of hypersomnolence that are frequently associated with hyperphagia and hypersexual behaviors. The episodes may last 1 or 2 days or several weeks and are characterized by spending an overly long time in bed (16–18 hours). During this period, the patient sometimes can get up, eat, and go to the restroom. A change in personality, behavior, and psychological mood is frequently seen and also a stuporous appearance can be noticed.49,50
Sleepiness in Children It is a rare condition, 3 times more frequent in males than females and starts during adolescence. The pathophysiology is not conclusive, but some studies highlighted diffuse brain hypoperfusion (more pronounced in the thalamic and frontotemporal areas), viral and autoimmune causative factors based on the frequent report of flulike symptoms at onset. The most frequent precipitating factor (70%) is the presence of inflammatory lesions in the thalamus, diencephalon, and midbrain on postmortem neuropathology, suggesting a viral infection, increased frequency of the human leukocyte antigen DQB1*0201 allele, and, in a few cases, abnormalities in serotonin and dopamine metabolism, suggesting a neurotransmitter imbalance in the serotonergic or dopaminergic pathway. There are also some patients who started with somnolence after a head trauma.49,50 Polysomnography and MSLT are not required for diagnostic reasons. There is no treatment consensus. Lithium may be beneficial to reduce relapses, and modafinil may reduce duration of episodes. Recently, clarithromycin was also suggested as a treatment, but the effectiveness of this drug needs to be studied in more patients.51
Menstrual-Related Hypersomnia There is an association of hypersomnolence periods with menstruation. Patients experienced longer sleep nocturnal duration and daytime sleepiness. Polysomnography shows shortened sleep latency and normal architecture. A good response with anovulatory agents reinforces the suspicion of a hormonal origin of the condition.52,53
Hypersomnia Associated with Behaviorally Induced Insufficient Sleep Sleep deprivation in children and adolescents is considered a health concern. In the last century, children decreased sleep duration and now they are sleeping about 1 hour less compared with 100 years ago.11,54 Studies with sleep deprivation have shown the importance and necessity of having adequate sleep quality and duration.2 For children, it is believed, and easily seen in clinical practice, that sleep influences physical growth, emotional stability, behavior, and cognitive function, including memory consolidation. Studies have shown that insufficient sleep is associated with fatigue, attention problems, learning difficulties, impulse control, and organizational skills poverty. In children and adolescents, short sleep is associated with overweight and obesity, higher caloric intake derived from fat and lower caloric intake from carbohydrates, and insulin resistance.55,56
The medical literature from the last 50 years shows that concepts of modernity have been associated with overstimulation that predisposes children not getting the sleep that they need. Recently, the influence of electronic media including video games, cell phones, and the Internet were implicated in increased night-time activity and affected sleep patterns of not only in adults, but also in children and adolescents. Strategies to reduce sleep deprivation are necessary to prevent damages during developmental ages and to promote a better quality of sleep for all.4,55,56
Hypersomnia Associated with Circadian Rhythm Disorder Delayed sleep phase syndrome is a circadian rhythm disorder characterized by a constitutional inability to anticipate sleep and a tendency to fall asleep at progressively later times at night. Because sleep-onset time is often as late as 1 to 3 AM, children and adolescents with this disorder are often sleep deprived on school nights and are consequently sleepy during the daytime.57 Although delayed sleep phase syndrome has its peak incidence during adolescence, many children already have symptoms in prepubertal years. If allowed to sleep uninterrupted, as happens on weekends or holidays, the individual may sleep until noon and feel refreshed. There is no qualitative or quantitative abnormality in sleep. Sleep onset and offset are simply at socially inappropriate times and lead to daytime sleepiness when the patient has to conform to the societal norms for attending school or work. Complaints of difficulty of sleeping early at night are viewed as insomnia. In the morning, patients manifest chronic hypersomnia. Being late or absent to school becomes a serious problem. Delayed sleep phase syndrome is related to a dysfunction of the suprachiasmatic nucleus, which is our circadian timekeeper. Patients show a delay in the timing of release of melatonin (a sleep-inducing hormone), and in reaching the nadir of the core body temperature, which corresponds with the time that a person is likely to be most sleepy.58 Delayed sleep phase syndrome may be associated with certain polymorphisms in the PER3 circadian gene.59 Treatment consists of keeping a rigid morning wake up time 7 days a week, early exposure to bright sunlight for 30 minutes immediately on awakening in the morning, and oral melatonin before the desired bedtime.60
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