Chapter 509. Sleep Disorders

A survey from the National Sleep Foundation (NSF) shows that 69% of children under 10 years of age experience some type of sleep disturbance.1 Significant sleep problems affect 25% to 40% of children and adolescents.2 These sleep problems tend to persist to adulthood if left untreated. Despite the high prevalence of sleep problems, most pediatricians do not ask question about children’s sleep. The survey from community practice shows that pediatricians acknowledge the importance of sleep problems, but they fail to screen adequately for them, especially in older children and adolescents.3 Untreated sleep disorders can lead to long-term consequences. Several studies have demonstrated the association between sleep disorders and cardiovascular and neurocognitive complications. Therefore, it is crucial that pediatricians recognize the signs and symptoms of sleep disorders and integrate sleep issues as part of the routine health maintenance. In this chapter, normal sleep development and the common sleep problems encountered in general pediatric practices are discussed. Obstructive sleep apnea is reviewed in Chapter 508.

Knowledge of sleep regulation, normal sleep, and its change during development is essential to understand and recognize sleep disorders in children and adolescents. Certain features of sleep help in the diagnosis of sleep disorders. For example, night terror, a phenomenon that occurs in nonrapid eye movement (NREM) sleep, is more likely to occur during the first part of the night when NREM predominates, while nightmares, a rapid eye movement (REM) phenomenon, are common during the latter part of the night. Sleep is the result of complex interaction between sleep- and wake-promoting neurons. The sleep-promoting neurons are located in the ventrolateral preoptic nucleus, which contains GABA-ergic (Gamma-amino-butyric acid) and galaninergic neurons. The awake-promoting neurons are located in the posterior lateral hypothalamus, which contains orexin/hypocretin neurons. A model is proposed in which wake- and sleep-promoting neurons inhibit each other, which results in stable wakefulness and sleep.4 Sleep and alertness are regulated by 2 important factors: the homeostatic factor, which depends on prior sleep duration and quality and awakening time and the circadian rhythm or intrinsic biological clock. These 2 forces interact and allow the diurnal pattern of sleep with consolidated sleep at night and wakefulness during daytime. Two “sleepiness” periods occur in humans. The first occurs at night between midnight and 6.00 am and the second in the early afternoon.5 The circadian rhythm is affected by several environmental cues (zeitgebers), such as social interaction and timing of meals, but the most important environmental cue is light exposure, which has different effects on the biological clock depending on the time of exposure.

Normal human sleep comprises 2 major stages, NREM and REM sleep, based on the characteristic of the electroencephalogram, electromyogram, and electrooculogram.6 NREM sleep is subdivided into 4 stages. Stage 1 is defined by an attenuation of high-frequency alpha wave (8–13 Hz); the presence of low-amplitude, mixed-frequency electroencephalogram (theta wave, 4–7 Hz); a slight decrease in chin electromyogram from awake; vertex sharp waves; and slow, rolling eye movements (eFig. 509.1). Stage 1 accounts for 3% to 8% of total sleep time. Stage 2 is characterized by the presence of sleep spindles (distinct waves with frequency 12–14 Hz) and K-complex (negative sharp wave followed by a positive component) (eFig. 509.2). Humans normally spend 45% to 55% of total sleep time in stage 2, and it is the most prevalent stage of sleep. Stages 3 and 4 are typified by increased slow-wave sleep (> 20% for stage 3 and > 50% for stage 4; eFigs. 509.3 and 509.4). Stages 3 and 4 account for 15% to 20% of total sleep time. REM sleep is characterized by a significant decrease in chin electromyogram; the presence of low-amplitude, mixed-frequency electroencephalogram pattern; and the occurrence of rapid eye movement (eFig. 509.5). Stage REM accounts for 20% to 25% of total sleep time.

Sleep pattern and sleep architecture undergo developmental changes from infancy to adolescence. Sleep in infants has several features that are different from children and adults (Table 509-1). Active or REM sleep is approximately 50% and is the dominant state of sleep. Quiet or NREM sleep accounts for only 35% to 45% of total sleep time. REM sleep in premature infants can be as high as 80% of total sleep time. The percentage of REM sleep decreases with increasing age and reaches an adult proportion by 5 to 6 years of age. The sleep cycle (the total duration of NREM and REM in 1 cycle) of infants is 50 to 60 minutes, while that of adults is 90 to 100 minutes. In infants, NREM and REM sleep distribute equally throughout the night. In contrast, in older children and adults, NREM sleep predominates in the first part of the night, while REM sleep predominates in the latter part of the night. Another distinct feature of infant sleep is that the entry of sleep is through REM sleep, while that of children and adults is through NREM sleep. Normal full-term neonates spend most of their time sleeping (16–18 h/day).7 Sleep pattern in infants is polymorphic with multiple naps during the day. Infants begin to consolidate their sleep by about 3 months. By age 12 months, infants will have a long nighttime sleep and 2 daytime naps. At age 18 months, the naps are decreased from 2 to 1. At age 5 years, 75% of children give up their naps, but social and cultural difference may influence this pattern. By age 6 years, children sleep approximately 10 to 11 hours, and the sleep need does not change until adolescence.

Sleep in adolescents has unique features as a result of physiologic changes during puberty. The major change is a shift in melatonin secretion and circadian sleep phase, leading to phase delay with propensity to later onset of sleep and later wake-up time.8 In addition, social and academic demands during this period can predispose adolescents to sleep deprivation.9 Some adolescents cope with this problem by sleeping longer during the weekend, which can make the phase delay worse. Studies show that adolescents need 9 hours of sleep, and the sleep need in adolescents does not change across the adolescent span (10–17 years).8 However, most adolescents sleep only 7 to 7.5 hours each night, which results in significant sleep debt over time. Only 15% of adolescents sleep 8.5 or more hours on school nights, and 26% of high school students sleep 6.5 hours or less each school night.10 Adolescent also have irregular sleep patterns, which could contribute to shift in sleep phase. The average increase of weekend over weekday sleep is almost 2 hours per night.10 Sleep debts in adolescents can lead to significant long-term consequences, including daytime sleepiness and changes in mood, attention, memory, behavior, and academic performance.

Restless Legs Syndrome and Periodic Limb Movement Disorders

Periodic limb movement in sleep is characterized by periodic episodes of repetitive and highly stereotypic limb movements.11 Periodic limb movement disorder (PLMD) is defined by the presence of periodic limb movements during sleep associated with symptoms of insomnia or excessive daytime sleepiness.11 Restless legs syndrome (RLS) is a clinical diagnosis characterized by disagreeable leg sensations that usually occur prior to sleep onset. RLS and PLMD are common in adults, with a prevalence of 4% to 10%.12 The prevalence in children has not been well studied, although approximately 30% to 40% of adult patients report the onset of RLS symptoms before the age of 20.13 One recent study reports the prevalence of RLS is 1.9% in children 8 to 11 years old and 2.0% in children 12 to 17 years old.14 The prevalence of RLS in boys and girls is similar,14 while the female-to-male ratio is 2:1 in adult RLS.15 Children with RLS and PLMD may present with nonspecific symptoms such as growing pains, restless sleep, and hyperactivity.16 These symptoms are often not noticed by parents, although a family history of RLS and PLMD is common.17 Several studies show the strong association between attention deficit hyperactivity disorder (ADHD) and RLS and PLMD. The relation is somewhat complex. It is estimated that 10% to 30% of children with ADHD may have RLS and PLMD.12,17 In addition, 44% of children with RLS have been found to have ADHD or ADHD symptoms.18 This association has many possible explanations.18 Sleep disruption associated with RLS and PLMD might lead to inattentiveness and hyperactivity; RLS and PLMD may be a comorbidity of ADHD; RLS and PLMD and a subset of ADHD may share a common dopamine abnormality; and diurnal manifestations of RLS and PLMD might mimic ADHD.

The etiology of RLS and PLMD is not known. Several studies show the role of genetics, dopamine dysfunction, and low iron stores in the pathophysiology of RLS and PLMD. A recent study shows the association between PLMD and a common variant in an intron of the protein BTBD9 on chromosome 6p21.2.19 Many children with RLS and PLMD have low iron storage, as evidenced by low serum ferritin and/or iron.20,21 Several conditions are associated with increased risk of RLS and PLMD (secondary RLS), including pregnancy, uremia, iron deficiency, and anemia.

The diagnosis of RLS and PLMD requires specific diagnostic criteria. The 4 classic, essential adult criteria for RLS include (1) the urge to move the legs, (2) worsening of the urge during rest, (3) relief by movement, and (4) worsening during the evening and at night.22 Children present a diagnostic challenge because of the inability to describe classic leg paresthesia. The international RLS study group has developed criteria for making a diagnosis of RLS and PLMD in children (Tables 509-2 and 509-3).12 In addition to essential adult criteria, children should be able to provide age-appropriate descriptions of leg discomfort, such as tickle, spiders, bugs, or energy in my legs. In children who are unable to describe their symptoms, other supportive criteria are needed, including sleep disturbance for age, a family history of RLS, and a polysomnographic finding of periodic limb movements in sleep (index of 5 or more per hour of sleep). For PLMD, the diagnosis requires a polysomnographic study to establish a minimum periodic limb movement index of 5 or more per hour. Periodic limb movements in sleep are characterized by a sequence of 4 or more limb movements with duration of 0.5 to 5 seconds and separated by an interval of more than 5 seconds and less than 90 seconds (Fig. 509-1). Sleep disturbance, including sleep onset and sleep maintenance problems and daytime sleepiness, is an important part of the diagnostic criteria of PLMD. Because sleep-related respiratory abnormalities such as obstructive sleep apnea and upper airway resistance syndrome can lead to arousals associated with limb movements, movements following respiratory events are excluded.23 Therefore, respiratory monitoring including nasal airflow and respiratory efforts are essential in making a diagnosis of PLMD.

Treatment of RLS and PLMD includes nonpharmacologic and pharmacologic therapy. The importance nonpharmacologic intervention such as avoidance of caffeine and good sleep hygiene cannot be overemphasized. Children with low iron stores (ferritin < 50 μg/L) can benefit from iron therapy with 3 mg/kg/day of elemental iron for 3 months.21 Currently, there is no FDA-approved medication available to treat RLS and PLMD in children. Although there is limited information in children,24 few studies show the benefit of dopaminergic medications in improving RLS and PLMD.17,25 In children with ADHD and associated RLS and PLMD, dopaminergic medication may improve ADHD symptoms.25 Benzodiazepines such as clonazepam can be useful when given in combination with other medications.

Rhythmic Movement Disorders

Rhythmic movement disorders are characterized by stereotypic body movements such as head banging, body rocking, and head rolling. These movements usually occur during the transition from wakefulness to sleep or following arousals to awake,26 but they may arise during any stage of sleep, including REM sleep.27 The movements last 5 to 15 minutes but may persist for several hours. They are quite common in infants and young children. It is estimated that 59% of all infants at 9 months of age exhibit sleep-related rhythmic movements. The prevalence decreases to 33% by 18 months and to 5% by 5 years.22 This condition is therefore benign and typically resolves spontaneously.26 However, significant injury may occur from repetitive movements.28 Diagnosis is based on obtaining a characteristic clinical history and excluding other medical and psychiatric disorders. Sleep studies are not usually needed. Treatment consists of support and reassurance. Safety prevention is important to make sure children are protected from injury during these episodes. In severe cases associated with injury and family disruption, medical therapy with tricyclic antidepressants and benzodiazepines such as clonazepam may be effective.29

Parasomnias

Parasomnias are defined as undesirable physical events or experiences that occur predominantly during entry into sleep, within sleep, or during arousals from sleep.22 Parasomnias can be subclassified into disorders of arousal from NREM sleep and parasomnias associated with REM sleep. Arousal disorders from NREM sleep consist of several common disorders in children, such as confusional arousals, sleep terror, and sleepwalking. Parasomnias associated with REM sleep include a common disorder such as nightmare and REM sleep behavior, a rare condition in children.

Disorders of Arousal from NREM Sleep: Confusional Arousals, Sleep Terrors, and Sleepwalking

These disorders, characterized by impaired or partial arousal from slow-wave sleep, are common in preschoolers and school-aged children, and they usually resolve spontaneously. In confusional arousals, children wake up suddenly, cry, speak unintelligible words, and may appear frightened. The prevalence rate of confusional arousals in children 3 to 13 years of age is 17%.22 Sleep terrors are associated with more intense manifestations and significant autonomic nervous system signs, including dilated pupils, diaphoresis, piloerection, tachypnea, and tachycardia. The prevalence rate of sleep terrors is 1% to 6.5% in children.22 Sleepwalking is characterized by repeated episodes of rising from bed during sleep and walking about. The events range from simply sitting up in bed to walking and even frantic attempts to “escape.”22 These episodes generally last a few minutes but may last much longer. The prevalence of sleepwalking in childhood is as high as 17%.22 Confusional arousals, sleep terrors, and sleepwalking usually occur in the first part of the night corresponding to prominent slow-wave sleep during this period. The children are not responsive to comforting measures, may not recognize parents, and have no recollection of the events upon awakening. The attempt to wake the child can prolong the event. These episodes can be precipitated by stress, sleep deprivation, anxiety, and environmental noises. A recent study suggests that other sleep disorders, such as sleep-disordered breathing and RLS, can precipitate these events, resulting in persistent parasomnia.30

Diagnosis of NREM arousal disorders includes obtaining a typical clinical history, with emphasis on detailed description, timing, and response to intervention. Differential diagnosis includes nocturnal partial complex seizure, frontal lobe seizure, nocturnal panic attack, nightmares, and posttraumatic stress disorder.31 There is no need for sleep studies in children with simple arousal disorders. A referral to a sleep center is indicated in children with an unusual presentation, persistent parasomnias, violent behaviors, or symptoms of other sleep disorders. There is no definite polysomnographic characteristic of disorders of arousals from NREM sleep. Polysomnography can support a clinical diagnosis by demonstrating precipitous arousals from slow-wave sleep (Fig. 509-2), especially if preceding the typical confusional arousals, sleep terrors, or sleepwalking. In addition, a sleep study can help to identify coexisting sleep disorders that could potentially precipitate arousals, such as obstructive sleep apnea,30 and to exclude conditions that can mimic partial arousal disorders, such as sleep-related epilepsy. Treatment is reassurance and good sleep hygiene in mild cases. Safety issues should be discussed to prevent accident or injury during the episode. Parents should be instructed not to intervene because it may prolong the events. Behavioral intervention may benefit some children. Coexisting and precipitating factors such as obstructive sleep apnea should be treated. In severe cases, pharmacologic therapy with benzodiazepine such as clonazepam may be indicated.

Nightmares

A nightmare is more common than confusional arousal and night terror. The prevalence is approximately 10% to 50% in preschool children.22 It equally affects boys and girls. In adolescents and young adults, nightmares are more frequently reported in females. It is characterized by frightening and coherent dreams that seem real and disturbing, resulting in anxiety and fear upon awakening.22 In contrast to confusional arousals and night terrors, nightmares usually occur during the latter part of the night when REM sleep predominates. The episode is usually not intense, with less autonomic agitation. Upon awakening, children are fully oriented, easily comforted, and have a clear recall of dream content.26 Return to sleep after the nightmare event is often delayed. The episode can be triggered by many factors, including traumatic events, stress, anxiety, and sleep deprivation. Certain medications, such as β-adrenergic blockers, amphetamines, dopamine agonists, hypnotic medications, and certain antibiotics (erythromycin), can precipitate nightmares.32 Withdrawal from REM suppressant medications such as tricyclic antidepressant and selective serotonin reuptake inhibitors can lead to REM rebound, which predisposes children to nightmares. Diagnosis is based on obtaining a typical clinical history. Polysomnographic evaluation is usually not required. It may be indicated in children with unusual presentations, violent behavior, or injury during the episode to exclude other parasomnias or nocturnal seizure.22 Treatment includes reassurance, education, and good sleep hygiene. Eliminating or minimizing precipitating factors is important in the management of nightmares. A small number of children with severe, persistent nightmares may require further medical and psychological evaluation.26

Narcolepsy

The prevalence of narcolepsy is approximately 1 in 1000 to 1 in 10,000 in the United States and 1 in 600 in Japan.33 The prevalence is equal among boys and girls. About 34% of patients with narcolepsy report onset of symptoms before 15 years of age, 16% before 10 years, and 4.5% before 5 years.34 However, the diagnosis of narcolepsy is made in only 4% of patients before 15 years of age.34 A family history of narcolepsy is present in 25% of cases. Certain human leucocyte antigen (HLA) genetic marker are common in patients with narcolepsy, including HLA-DR2 (DR 15) and HLA-DQ6 (HLA-DQB1*0602). Hypocretin/orexin deficiency has been shown to play a major role in the pathophysiology of narcolepsy. Hypocretin is a neuropeptide in the hypothalamus that plays a significant role in sleep regulation, energy homeostasis, and neuroendocrine function. Human narcoleptics have 85% to 95% reduction in the number of hypocretin neurons.35 In addition, hypocretin deficiency is closely related to the presence of cataplexy and HLA-DQ1*0602.36 A decreased hypocretin activation of cholinergic neurons in the brainstem and basal forebrain may result in daytime sleepiness in narcoleptic patients.37

Clinical manifestation of narcolepsy is characterized by narcolepsy tetrad, consisting of excessive daytime sleepiness, cataplexy, hypnagogic hallucination, and sleep paralysis. Children with narcolepsy may present with a reappearance of daytime napping in a child who had previously discontinued naps.22 In addition, narcolepsy in children has certain features that are different from those in adults. Naps in children are longer and not refreshing compared to adults.38 Cataplexy or sudden loss of muscle tone triggered by emotional events may develop 5 to 10 years after the onset of hypersomnia.38 Hypnagogic hallucination is visual, auditory, or tactile and is vivid and often frightening. It typically occurs at sleep onset, often with realistic awareness of the presence of someone or something.22 Patients may report unusual experiences such as being caught in a fire, impending attack by a stranger, or flying through the air.22 Sleep paralysis is a transient, generalized inability to move or speak during the transition between sleep and wakefulness. It is a frightening experience and often occurs with hypnagogic hallucination.22 Because of these unusual experiences, some children with narcolepsy may be misdiagnosed with psychiatric disorders or behavior problems.39 Furthermore, children often present with unspecific symptoms, including learning disability, poor concentration, emotional labiality, and social isolation.

Diagnosis is based on obtaining the typical clinical history and diagnostic sleep study. The differential diagnosis includes delayed sleep phase syndrome; chronic sleep deprivation; psychiatric disorders, especially depression; substance abuse; idiopathic hypersomnia; and recurrent hypersomnia (Kleine-Levin syndrome and menstrual-related hypersomnia). Secondary narcolepsy or narcolepsy due to other medical conditions include several neurological disorders such as hypothalamic tumor, Neiman-Pick type C disease, head trauma, multiple sclerosis, myotonic dystrophy, Prader-Willi syndrome, Parkinson disease, and multiple-system atrophy. The specific test for narcolepsy is overnight polysomnography with a multiple sleep latency test (MSLT). The overnight polysomnography is required before the MSLT to evaluate overall sleep quality and to exclude other causes of hypersomnia, such as obstructive sleep apnea. The MSLT is performed by allowing children to take multiple naps in a dark room during daytime. Children with narcolepsy demonstrate pathologic sleepiness with short sleep latency and early REM onset during short naps (Fig. 509-3). The typical characteristic of MSLT in narcoleptic patients include sleep latency of less than 8 minutes and the presence of more than 2 REM onsets in 5 naps.22 Children present diagnostic challenges for interpretation of MSLT. Sleep propensity in children changes with maturation and Tanner staging.40 There is limited normative data for sleep latency during MLST in young children. In addition, MSLT in narcoleptic children during the early stage may not show typical early REM onset. Therefore, serial polysomnograms and MSLT are needed to establish a diagnosis in children who are sleepy with no obvious explanation.41 The other diagnostic tool is measurement of levels of hypocretin-1 in the cerebrospinal fluid, which is highly specific and sensitive for narcolepsy with cataplexy. Hypocretin-1 in the cerebrospinal fluid less than or equal to 110 pg/mL, or one third of mean normal control value, is used in the diagnosis of narcolepsy.42 This test may be useful when the patient is too young to perform an MSLT.22

Pharmacologic therapy in children involves the use of stimulant medications and REM suppressant medications.43 Stimulant medications are awake-promoting agents that help to alleviate daytime sleepiness. The common stimulant medications include schedule II control substances such as methylphenidate and dextroamphetamine. Pemoline has been taken off the market because of significant liver side effects. Modafinil (schedule IV) is a new generation of stimulant medication with relatively fewer problems of drug tolerance and addiction. REM suppressant medications are effective in managing patients with other accessory symptoms of narcolepsy, including cataplexy, hypnagogic hallucination, and sleep paralysis. The common REM suppressant medications used in children include tricyclic antidepressant and selective serotonin reuptake inhibitor (specific serotonin reuptake inhibitor). Nonpharmacologic therapy is important in children with narcolepsy. Patients and their family should be educated about the chronic nature of the condition. Parents, teachers, and employers should be aware of the symptoms of narcolepsy to avoid confusing the child’s behavior with laziness, hostility, rejection, or lack of interest and motivation. Children with narcolepsy can lead productive lives if they are provided proper medical care. If possible, patients with narcolepsy should avoid jobs that require driving long distances or handling hazards or that require alertness for lengthy periods. Children with narcolepsy should practice good sleep hygiene, including regular sleep routine. Some children may benefit from scheduled short naps. It is essential to discuss safety issue with patients and their families.

Behavior Insomnia

Behavior insomnias are the most common sleep disorders in children. These disorders are the result of interaction between normal developmental changes in circadian rhythm and parental reaction to those changes. There are 3 main types: sleep-onset association type, limit-setting type, and combined type. Sleep-onset association type is characterized by the child’s dependency on specific objects or settings for initiating sleep or returning to sleep following an awakening.22 Limit-setting type is characterized by bedtime stalling or bedtime refusal that is the result of inadequate time setting by a caregiver.22 The prevalence is estimated to be 10% to 30% of children. There is a slightly increased incidence in boys.

In sleep-onset association type, children associate their sleep with specific soothing procedures (eg, rocking, car rides, watching television) or objects (eg, bottles, parents’ bed), or settings (lighted condition). These children experience difficulty falling asleep at bedtime and upon nighttime awakening without particular conditions associated with falling asleep, such as the presence of parents. When those conditions are established, the children resume sleep relatively quickly. In limit-setting type, children stall or refuse to go to sleep, leading to sleep-onset delay. Some children may present with nighttime fears, which are the manifestation of bedtime stalling. The problems often result from parental difficulties in setting limits and enforcing a regular bedtime. In some parents, inconsistent or lack of bedtime rules can lead to prolonged bedtime struggles or bedtime refusal behavior. When parents enforce limits, sleep often occurs quickly.

The diagnosis is based on a typical clinical description from parents or other caregivers. Behavior insomnia of childhood is quite common even in healthy children; therefore, the parents or caregivers must perceive this sleep issue as highly problematic or demanding. Because infants do not develop regular sleep patterns until 3 to 6 months of age, the diagnosis cannot be entertained before 6 months.44 The American Academy of Sleep Medicine has developed guidelines for diagnosing behavior insomnia of childhood. In sleep-onset association type, the following features are present: (1) Falling asleep is an extended process that requires special conditions. (2) Sleep-onset associations are highly problematic or demanding. (3) In the absence of the associated conditions, sleep onset is significantly delayed or sleep is otherwise disrupted. (4) Nighttime awakenings require caregiver intervention for the child to return to sleep. Limit-setting type includes each of the following: (1) The individual has difficulty initiating or maintaining sleep. (2) The individual stalls or refuses to go to bed at an appropriate time or refuses to return to bed following a nighttime awakening. (3) The caregiver demonstrates insufficient or inappropriate limit setting to establish appropriate sleeping behavior in the child. In both types, the sleep problem is not explained by another sleep disorder, medical or neurological disorder, mental disorder, or medication use.22 The sleep study is not required unless patients have symptoms of other sleep disorders.

Treatment for the sleep-onset association type includes good sleep hygiene and behavioral interventions. The extinction process involves steps to reduce parental assistance and allows children to relearn the sleep association with their own bed environment. This intervention is labor intensive and can be difficult in some children. Therefore, it is important that the pediatrician is sensitive to both the parent’s and child’s need. In the limit-setting type, children may benefit from good sleep hygiene, establishing bedtime routines, and positive reinforcement. Several studies have shown that behavioral interventions are effective and recommended in the treatment of bedtime problems and night waking in young children.45

Delayed Sleep Phase Syndrome

Delayed sleep phase syndrome (DSPS) is a common sleep disorder in teenagers and young adults with an estimated prevalence of 7% to 16%.22 It is also the major cause of sleep deprivation in this age group. The onset usually starts during adolescence but may begin in early childhood. DSPS is classified in the circadian rhythm disorders. It is characterized by sleep-onset delay in relation to desired sleep time, resulting in sleep-onset insomnia and/or difficulty awakening at the desired time. The precise mechanisms underlying DSPS are currently unknown. An abnormal interaction between the endogenous circadian rhythm and the sleep homeostatic process may play an important role in the pathophysiology of DSPS.22 Certain genetic markers such as polymorphism in the circadian clock gene called hPer3 (a length polymorphism in the human Per3 gene) are associated with DSPS.46 In fact, a positive family history is present in approximately 40% of patients with DSPS.

Clinical manifestations include difficulty falling asleep but no problem maintaining sleep. These children and adolescents are sleepy when they have to conform to conventional sleep-wake schedules. However, when they are allowed to choose their preferred sleep time, they exhibit normal sleep quality and duration.22 The sleep deprivation in patients with DSPS can result in daytime sleepiness, decreased school performance, behavior problems, and mood disturbance. Diagnosis can be made by obtaining a typical clinical history. A sleep diary or actigraphy is beneficial in documenting the delayed sleep phase pattern. There is no need for polysomnography for making the diagnosis. Differential diagnosis includes normal sleep pattern with delayed schedule, sleep deprivation, depression, or substance abuse. Some adolescents and young adults maintain a delayed sleep schedule without impaired function. DSPS should be differentiated from school avoidance and antisocial behavior in adolescents.47

The management involves specific interventions to shift the sleep phase back to socially acceptable time. These interventions include light therapy, chronotherapy, and pharmacotherapy. The light affects circadian rhythm- in a phase-dependent manner, which means that light has different effects on the human biological clock (circadian rhythm) depending on the time of administration. Bright light exposure in the early morning hours advances the circadian rhythm, while light in the afternoon delays the rhythm. In fact, 2 hours of bright light exposure in the morning along with light restriction in the evening has been shown to be effective in shifting the phase back to desirable time in patients with DSPS.48 For patients living in areas with limited sunlight, commercially available light boxes can provide an alternative light source. Minimum effective light intensity is 2,500 lux. Chronotherapy is done by having patients intentionally delay or advance sleep onset by a few hours every day until sleep occurs at the desired time.49 The process is time consuming and needs close parental involvement in children and adolescents. The sleep environment during chronotherapy should be optimal with a dark and quiet room during the sleep portion of this process. Pharmacotherapy with melatonin can be used as adjunct therapy for patients with DSPS. The effect of melatonin on circadian rhythm is also phase dependent, but the phase response curve is in the opposite direction of light exposure.50 Melatonin administration in the evening and early night will advance the circadian phase, while its administration in the morning will delay the phase. In patients with DSPS, administration of melatonin in the evening is shown to be effective to advance the circadian phase, shorten sleep-onset time, and improve quality of life.51,52 The low dose of melatonin (0.5 mg) is as effective as a higher dose (3 mg). Timing of administration is crucial; the maximal effect occurs when melatonin is given 6.5 hours prior to dim-light onset.53 Patients with DSPS should have a regular sleep routine and should minimize variation in sleep and wake-up time from weekdays to weekends.

Since pediatric sleep disorders are quite common, it is important that pediatricians learn how to recognize and perform initial assessment of sleep problems. The understanding of normal sleep and its maturation is essential. The screening process for sleep problems can be integrated into routine health visits. Owens and Mindell developed sleep screening tools called BEARS for various ages to be used in a general pediatric office (eTable 509.1).54 The BEARS instrument provides a comprehensive screening process for the common sleep disorders in children between 2 and 18 years old. Since parents may not be aware of sleep problems in their children, it is important to ask both children and their parents about these issues.

In children and adolescents whose screening process reveals suspected sleep problems, it is important to obtain a further sleep history. The sleep habits include the bedtime and wake-up time during weekdays and weekends, sleep onset, night awakenings, and daytime naps. In children who snore at night, inquiries of other associated symptoms of sleep-disordered breathing should be raised, such as respiratory pauses, gasping or choking during sleep, mouth breathing, and morning headaches. For children with suspected movement disorders during sleep, symptoms of leg discomfort and abnormal movements of arms and legs should be obtained. The presence of other parasomnias, especially nightmares, night terrors, sleepwalking, and violent behavior during sleep should be reviewed. Children with hypersomnia should be assessed for other accessory symptoms of narcolepsy, including cataplexy, hypnagogic or hypnopompic hallucination, and sleep paralysis. The degree of daytime sleepiness can be assessed by asking about sleep propensity during various daytime activities, such as during school class, while watching television, and while taking a shower. It is important to evaluate the effect of sleep disturbances on neurocognitive function, particularly school performance, attention problems, and hyperactivity disorder. Details of sleep environments, such as night light, level of noise, room temperature, and television in the bedroom, should be sought. Other sleep issues, such as cosleeping, bedtime refusal, and bedtime stalling, should be addressed. Because several medications can affect sleep, a detailed medical history, including current medications, caffeine, alcohol consumption, and cigarette smoking, should be obtained. In the past medical history, attention should be directed to risk factors for sleep-disordered breathing (eg, history of frequent pharyngitis or tonsillitis, allergic rhinitis, or sinusitis). Certain medical conditions can be associated with specific sleep disorders, such as RLS and PLMD (iron deficiency anemia, renal diseases) and secondary narcolepsy (brain tumor, Prader-Willi syndrome, myotonic dystrophy). Psychiatric history, such as of depression, bipolar disorder, and anxiety disorder, should be obtained. It is essential to inquire about family history of sleep disorders, including sleep apnea, RLS, PLMD, narcolepsy, and parasomnias.

During physical examination, attention should be directed to physical features that are vulnerable to sleep apnea, such as obesity, nasal area (boggy nasal turbinate, reduced nasal airflow), oropharyngeal areas (tonsillar hypertrophy, large tongue base, long uvula, crowded oropharynx), and craniofacial anomalies (adenoid facies, steep and retroposition of mandibular plane, maxillary hypoplasia, long face). Children with suspected RLS, PLMD, or narcolepsy should have a complete neurological examination. It is important to keep in mind that children with sleep disorders may have a normal physical examination.

Children with suspected sleep disorders should be referred to pediatric sleep centers for further evaluation. Several studies have shown that the clinical history and examination may not reliably discriminate between primary snoring and obstructive sleep apnea syndrome.55,56 Further evaluation in the sleep center includes subjective evaluation (sleep diary) and objective evaluation, including actigraphy, polysomnographic study, and other specialized tests such as MSLT. Sleep diary and actigraphy can provide longitudinal assessment of sleep schedule. They are useful in evaluation of patients with insomnia and circadian disorders such as DSPS. Polysomnographic study is the diagnostic tool of choice for most sleep disorders. In addition to identifying sleep-related abnormalities, polysomnography provides information on the effect of sleep disorders on sleep quantity and quality. The standard montage used in the pediatric laboratory measures multiple physiologic parameters, including electroencephalogram, electrooculogram, chin electromyogram, leg electromyogram, electrocardiogram, nasal airflow, chest and abdominal movements, oxygen saturation, and end-tidal PCO2.