Pediatric Sleep Disorders

Pediatric sleep disorders increasingly interfere with daily patient and family functioning. Interest in and treatment of sleep disturbances in youth continues to grow, but research lags. One survey indicated that pediatricians were more likely to prescribe antidepressant medications for insomnia than psychiatrists.[1] Further investigation is needed to develop empirically based diagnosis and treatment of pediatric sleep disorders.

The consequences of untreated sleep problems may include significant emotional, behavioral, and cognitive dysfunction. The magnitude of these sequelae is inversely proportional to the child’s overall ability to adapt and develop in spite of the sleep disturbance. Sleep regulation remains a critical part of health for youths. Elevated rates of sleep problems exist among children and adolescents with neurodevelopmental, nonpsychiatric medical conditions and psychiatric disorders.

Reciprocal relationships occur between sleep disorders and comorbid psychiatric disorders. For example, when a given child with recurrent depression has an exacerbation, sleep problems often increase simultaneously. On the other hand, disrupted and inadequate sleep alone can produce behavioral, affective, and cognitive dysfunction.

Neurobiologically, closely linked modulatory systems appear to regulate sleep, alertness, and attention span. This article focuses on the most prevalent sleep problems among youths that are typical and distinctly unique from adult sleep disorders. Night terrors, nightmares, and sleep apnea are covered only briefly.

Major scientific advances have altered the understanding of sleep disorders, which have resulted in major changes moving from Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition Text Revision (DSM-IV-TR)[2] to the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5).[3] The DSM-IV-TR divided sleep disorders into 3 categories: Dyssomnias, Parasomnias, and Medical Psychiatric Disorders.

These categorical differences were eliminated in the DSM-5 to encourage the understanding that medical disorders and sleep disorders are intertwined and primary causation is usually not important. The entire section has been renamed Sleep-Wake Disorders to highlight that etiology may be based in the inability to maintain alertness during the waking period. The definition of dyssomnia versus parasomnia is provided to highlight the developmental differences of sleep-wake disorders.

Patients with dyssomnias present with difficulty initiating or maintaining sleep or with excessive daytime somnolence. The DSM-IV-TR defined dyssomnias as primary disturbances in the quantity, quality, or timing of sleep.[2] These disorders are believed to be a consequence of central nervous system (CNS) abnormalities that alter the sleep process. Adolescents with and without substance use disorders represent a significant proportion of sleep-disordered youths. This is an excellent example how difficult it may be to distinguish a primary sleep disorder from those induced by medical conditions.

Parasomnias result in disruption of an existing state of sleep. Arousals, partial arousals, and sleep-stage transition impositions define this category. An alternative definition of these phenomena includes deviated behavioral or physiologic events that transpire during sleep, specific sleep stages, or sleep-wake transitions. Insomnia or excessive sleepiness is uncommon in parasomnias despite intrusion upon sleep; these symptoms are characteristic of dyssomnia.

Most parasomnias affect otherwise healthy youths and commonly subside over the course of adolescence. These disorders are typically viewed as transient developmental phenomena, though children with parasomnias have been found to display higher rates of sleep-onset delay, night awakenings, bedtime resistance, and reduced sleep duration compared to a community control group.

Medical-psychiatric–associated sleep disorders comprise the neuropsychiatric conditions that typically include sleep disturbances. This category has been eliminated in DSM-5 but should still be considered by the clinician when evaluating sleep disorders. The medical differential should include the following:

• Attention deficit hyperactivity disorder (ADHD)

• Gastroesophageal reflux disease (GERD)

• Pervasive developmental disorders

• Mental retardation

• Down syndrome

• Prader-Willi syndrome

• Smith-Magenis syndrome

• Tourette disorder

• Nocturnal asthma

• Depressive disorders

• Anxiety disorders

• Mania

• Neuromuscular disorders

• Nocturnal seizures

• Kleine-Levin syndrome or periodic hypersomnia

• Chronic fatigue syndrome

• Headaches

• Blindness with associated sleep disorder

Insomnia disorder

Insomnia disorder, classified in DSM-5, which in DSM-IV was described as primary hypersomnia, includes normal sleep efficiency, sleep-wake cycles, and sleep architecture. Patients present with a normal variant sleep pattern except for dissatisfaction with sleep quantity or quality. This may be a lifelong pattern. The problems with sleep are often associated with the following:

• Difficulty initiating sleep: In children, this includes difficult initiating sleep without a caregiver

• Difficulty maintaining sleep: In children, this includes difficulty returning to sleep without caregiver

• Early morning awakening with difficulty returning to sleep

Other criteria for insomnia disorder require significant distress or impairment, occurring 3 nights per week, present for at least 3 months, and occurring despite sufficient time for sleep. The insomnia is not better explained or occurs exclusively in conjunction with another sleep-wake disorder. The insomnia is not due to the physiological effects of a substance, and coexisting mental/medical conditions do not fully explain the insomnia. If an individual reports feeling unrested (nonrestorative sleep) despite adequate duration and no difficulty initiating or maintaining sleep, then a diagnosis of unspecified insomnia disorder is given.

Difficulty initiating sleep means that the subjective sleep latency is greater than 20-30 minutes. Difficulty maintaining sleep is the subjective time awake after sleep onset is longer than 20-30 minutes. There is no standard definition of early morning awakening, but it usually requires awakening 30 minutes before the scheduled time or before total sleep time reaches 6.5 hours. When considering the final awakening time, it is also important to consider when bedtime occurs. For example, a child who initiates sleep at 7 pm versus 9 pm and awakens at 5 am may need to go to bed later.

The pathogenesis of insomnia disorder is poorly defined. First episode often occurs in young adulthood. However, it can also begin in childhood or adolescence. It can be associated with life changes and resolve when the precipitating event subsides. For some, the insomnia can persist because of conditioned arousal from the precipitating event. In children, the conditioned factors include needing a parent to be present to initiate sleep, but they can also include absence of a consistent sleep schedule. In adolescents, insomnia is more often triggered by irregular sleep schedules. Polysomnography (PSG) is of limited value in evaluating insomnia disorder in children.[4]

Hypersomnolence disorder

Hypersomnolence disorder as described in DSM-5 is the self-reported excessive need for sleep despite sleeping for at least 7 hours and having at least one of the following symptoms:

• Recurrent periods of sleep or naps within the same day

• A prolonged sleep of more than 9 hours per day that is not refreshing

• Difficulty being fully awake after abrupt awakening

Individuals with hypersomnolence disorder usually fall asleep quickly and have good sleep efficiency (>90%). Despite this, they have sleep inertia/drunkenness, where they have difficulty waking up and appear confused, combative, or ataxic. They can also experience automatic behavior during which they carry out simple routines like driving, have no recall of going several miles, then realize they are several miles from where they thought they were. Naps are not refreshing despite lasting more than 1 hour. Individuals are at risk for autonomic nervous dysfunction such as recurrent vascular-type headaches, Raynaud phenomena, and fainting. The disorder usually begins in late adolescence, at a mean age of 17-24 years.

Hypersomnolence can be increased temporarily by stress and alcohol use. Viral infections have preceded or accompanied hypersomnolence in 10% of cases, sometimes several months after the infection. Head trauma can result in hypersomnolence within 6-18 months after injury. An autosomal dominant mode of inheritance occurs in a subset of familial cases.

Nocturnal PSG findings include normal-to-prolonged sleep duration, short sleep latency (< 8 min), normal-to-increased sleep continuity, and normal distribution of rapid eye movement (REM) sleep but increased amounts of slow-wave sleep. During naps, sleep-onset REM may be present but may occur less than 2 times in 4-5 nap opportunities.

Behaviorally induced insufficient sleep syndrome may produce symptoms of daytime sleepiness and resemble hypersomnolence disorder. Individuals with inadequate sleep "catch up" when they are free from social/academic/occupational demands. After 10-14 days of catch-up sleep, the diagnosis may be clearer.

Narcolepsy

Narcolepsy is defined by DSM-5 as recurrent periods of an irrepressible need to sleep, lapsing into sleep, or napping that occurs within the same day. This must occur 3 times per week over 3 months. It also requires one of the following to be present:

• Episodes of cataplexy occurring a few times per month: Cataplexy is defined as (1) in individuals with chronic disease, as having brief (seconds to minutes) episodes of sudden loss of muscle tone with maintained consciousness that are triggered by laughter or joking or (2) in children or individuals within 6 months of onset, spontaneous grimaces or jaw-opening episodes with tongue thrusting or a global hypotonia without any obvious emotional precipitants.

In pediatric patients, excessive daytime sleepiness is the most common first symptom of narcolepsy.[5] Symptom onset peaks at 15 years of age. Low hypocretin levels are present, they must occur in the absence of acute brain injury, inflammation, or infection. Nocturnal sleep PSG shows REM sleep latency to be less than or equal to 15 minutes or a multiple sleep latency test shows a mean sleep latency of less than or equal to 8 minutes with 2 or more sleep-onset REM periods.

REM sleep mechanisms are dysregulated in youths with narcolepsy, but evidence also exists of non-REM (NREM) and circadian sleep-wake cycle abnormalities. REM-associated sleep phenomena intrude into the awakened state. Sleep attacks (sleep), cataplexy (abrupt atony precipitated by strong emotions), and hypnagogic and hypnopompic hallucinations (experienced as dreamlike events immediately before sleep onset or upon awakening) are characteristic of narcolepsy.

Excessive daytime somnolence leading to irresistible or involuntary sleep (sleep attacks) may occur. The roles of the neuropeptide hypocretin and human leukocyte antigen (HLA)-DR2/DBQ1 as a genetic-neuroimmune interaction are being considered in current research on this issue. Narcolepsy is consistent with the polygenic model of development in most human cases. Narcolepsy triggered by streptococcus infections, H1N1 influenza, and H1N1 vaccination in genetically vulnerable individuals has been reported.[5]

Specifiers include the following:

• Narcolepsy Without Cataplexy But With Hypocretin Deficiency

• Narcolepsy With Cataplexy But Without Hypocretin Deficiency

• Autosomal Dominant Narcolepsy, Obesity, and Type 2 Diabetes

• Narcolepsy Secondary to Another Medical Condition

Narcolepsy can be diagnosed even when secondary to infections, trauma, or tumor, such as in Whipple disease or sarcoidosis. There is destruction of hypocretin neurons. Individuals who are HLA DQB1*06.02 positive may be more vulnerable to destruction of these neurons from an autoimmune process. Transient decreases in cerebrospinal fluid (CSF) hypocretin levels can occur without cell loss and can complicate the diagnosis. Functional imaging has demonstrated impaired hypothalamic responses.

Breathing-related sleep disorders

The International Classification of Sleep Disorders, 2nd Edition (ICSD-2) identifies 11 types of sleep-related breathing disorders. However, DSM-5 only recognizes 3: Obstructive Sleep Apnea Hypopnea, Central Sleep Apnea, and Sleep-Related Hypoventilation. This simplification is to facilitate the recognition of these sleep problems and referral for further evaluation.

Obstructive sleep apnea hypopnea

The pathophysiology of obstructive sleep apnea syndrome (OSAS) is poorly understood. Alterations exist in alveolar ventilation and oxygenation. OSAS is associated with adenotonsillar hypertrophy; however, most youths with adenotonsillar hypertrophy do not experience OSAS. Furthermore, adenotonsillectomy does not appear to resolve OSAS in many children.[6] Upper airway neuromotor dysfunction is possible in the initiation of OSAS. Obesity is now recognized as one of leading risk factors for increasing rates of OSAS.[7]  Snoring is common in OSAS, but some children with OSAS have no snoring reported by their families.[8] Certain medical conditions such as Prader-Willi syndrome or trisomy 21 (Down syndrome) increase the risk for OSAS because of midline deformities such as macroglossia, micrognathia, midface hypoplasia.

Obstructive sleep apnea hypopnea is defined by DSM-5 as evidence from PSG for at least 5 obstructive apnea or hypopneas per hour of sleep and either (1) nocturnal breathing disturbances (snoring, snorting/gasping, breathing pauses during sleep) or (2) daytime sleepiness, fatigue, or nonrefreshing sleep despite sufficient sleep opportunities; these occurrences cannot be explained by another mental disorder or medical condition. Alternatively, it can be diagnosed by PSG evidence of 15 or more obstructive apneas or hypopneas per hour of sleep, regardless of other symptoms. Research criteria used to identify children with OSAS is less stringent, setting the threshold of hypopneas at 1 to 5 events per hour.[8]

Central sleep apnea

Central sleep apnea is caused by variability in respiratory effort that results in repeated episodes of apneas and hypopneas during sleep. Central sleep apnea and obstructive sleep apnea hypopnea can coexist. DSM-5 defines central sleep apnea as PSG evidence of 5 or more central apneas per hour of sleep. The disorder is not better explained by another current sleep disorder.

There are 3 subtypes that can be diagnosed: idiopathic central sleep apnea, Cheyne-Stokes breathing, and central sleep apnea comorbid with opioid use. Idiopathic is characterized by variability in respiratory effort without evidence of airway obstruction. Cheyne-Stokes is a pattern of periodic crescendo-decrescendo variation in tidal volume of at least 5 events per hour, accompanied by frequent arousal. This pattern of breathing is associated with heart failure, stroke, or renal failure. Opioids affect the respiratory rhythm generators in the medulla (central area of brain) and the differential effects of hypoxic versus hypercapnic respiratory drive. This can occur even after only a one-time heavy use of the substance.

Sleep-related hypoventilation

In sleep-related hypoventilation, PSG demonstrates episodes of decreased respiration associated with elevated levels of carbon dioxide. In the absence of objective measures of carbon dioxide, persistent low levels of hemoglobin oxygen saturation dissociated from apneic/hypopneic events are also indicative. DSM-5 specifies that in order make this diagnosis, the condition is not better explained by another sleep disorder. In DSM-5, the 3 subtypes are idiopathic hypoventilation, congenital central alveolar hypoventilation, and comorbid sleep-related hypoventilation

Individuals with sleep-related hypoventilation may present with insomnia/sleepiness and/or headaches upon awakening. This disorder can coexist with obstructive sleep apnea hypopnea and central sleep apnea. Patients may have diaphragmatic weakness or ventilatory insufficiency resulting from pulmonary hypertension, cor pulmonale (right-sided heart failure), polycythemia, or neurocognitive dysfunction. Episodes of hypoventilation may be associated with frequent arousals or bradytachycardia. Hypoventilation cannot be present during wakefulness. Other causes of sleep-related hypoventilation include chronic obstructive pulmonary disease (COPD), neuromuscular disorders, and obesity.

Idiopathic and congenital central alveolar hypoventilation are extremely rare. Congenital central alveolar hypoventilation occurs in association with autonomic dysfunction or Hirschsprung disease. Some cases of idiopathic hypoventilation may be cases of late-onset congenital central alveolar hypoventilation.

Circadian sleep disorders

A circadian clock or oscillator located in the suprachiasmatic nuclei of the anterior hypothalamus influences the wakefulness or alertness phase. A circadian clock potentiates alternate or diurnal phases of the sleep-wake cycle. A free-running human sleep-wake cycle is 25 hours; however, the cycle entrained by the environment results in a 24-hour cycle.

In patients with circadian sleep disorders, sleep and associated processes are at opposite phases or periods. These disorders may represent a poor compensatory ability for sleep loss and include failure to adequately synchronize sleep-wake behaviors and adapt to environmental demands, such as school. They are frequently observed in adolescents with delayed sleep phase.

Circadian rhythm sleep-wake disorder as defined by DSM-5 is a persistent or recurrent pattern of sleep disruption that is primarily due to an alteration of the circadian system or to misalignment between the circadian rhythm and the sleep-wake schedule required. This sleep disruption leads to excessive sleepiness and/or insomnia. These symptoms cause significant impairment in functioning. Subtypes to be specified include the following:

• Delayed Sleep Phase Type

• Advanced Sleep Phase Type

• Irregular Sleep-Wake Type

• Non-24-Hour Sleep-Wake Type

• Shift Work Type

• Unspecified Type

The history usually consists of a delay in the timing of onset of sleep by more than 2 hours. When individuals are allowed to set their sleep schedule, sleep is normal in quality and duration. There is an increasing prevalence during adolescence, which may related to physiological and behavioral factors.

Some individuals may be hypersensitive to evening light, which delays their sleep onset. Others are hyposensitive to morning light and do not respond to the phase-advancing effects. There may be familial and sporadic forms involving mutations in circadian genes such as PER3 and CKIe.

Parasomnias

Parasomnias are sleep-related phenomena disrupting normal sleep that result in abnormal behavior, experiential events, or physiological events. Events can take place during sleep-wake transitions, arousal, or REM sleep. The relationship of events to sleep stage and other variables are related to pathogenesis .

NREM sleep arousal disorders

Individuals with NREM sleep arousal disorders, according to DSM-5, report recurrent episodes of incomplete awakening from sleep usually occurring during the first few hours of sleep. During the incomplete awakening, they may sleepwalk (sleep walking type) or panic (sleep terror type). Throughout the episode, the individuals are unresponsive to others who are trying to communicate with or comfort them. Individuals do not recall the events or dreams. The episodes are usually brief (1-10 min) but can last up to an hour.

Two specialized forms of sleepwalking include sleep-related eating and sex. The individuals may even ingest inappropriate foods. In sexsomnia, which occurs more often in males, there are varying degrees of sexual activity, including masturbation, fondling, groping, and sexual intercourse. Again, the individual has no memory of these events.

These disorders occur most frequently in childhood and diminish with age. Onset in adulthood should raise suspicion for other medical causes. These disorders are often familial, with a positive family history in 80% of individuals. "Confusional arousal" disorder is included by the International Classification of Sleep Disorders, 2nd Edition as an NREM sleep arousal disorder. Night terrors is the common name for sleep terror disorder.

Nightmare disorder

Repeated occurrences of extended, unpleasant, and well-remembered dreams that involve avoiding threats to survival, security, or physical integrity that occur during the second half of sleep is defined as nightmare disorder by DSM-5. When awakened, the individual is rapidly alert and oriented. The symptoms must cause clinically significant impairment or distress.

In contrast to NREM sleep arousal disorders, the prevalence of nightmare disorder increases through childhood and adolescence. Nightmares begin between ages 3 and 6 years and peak in late adolescence or early adulthood. Nightmares occur in the second half of sleep, whereas night terrors occur in the first few hours of sleep. Nightmares involve vivid recall, whereas individuals are amnestic for sleep terrors.

REM sleep behavior disorder

REM sleep behavior disorder as defined by DSM-5 involves repeated episodes of arousal during sleep associated with vocalization and/or complex motor behaviors. Since these behaviors arise during REM sleep, they usually occur more than 90 minutes after sleep onset and occur more frequent during the later part of sleep period. It usually does not occur during daytime naps.

Upon awakening from these episodes, the individual is completely awake, alert, and oriented. One of following also needs to be present: REM sleep without atonia on polysomnographic recording or a history if symptoms with an established synucleinopathy diagnosis (Parkinson disease, multiple system atrophy). The vocalizations or complex motor behaviors are usually responses to action-filled or violent dreams and are sometimes termed dream-enacting behaviors.

Nocturnal seizures may mimic REM sleep behavior disorder. However, these behaviors are more stereotyped. Symptoms in young individuals are usually an indication of narcolepsy or medication-induced REM sleep behavior disorder. Symptoms in young females are more likely to be caused by narcolepsy.

Restless legs syndrome (RLS)

Leg discomfort in patients with RLS is associated with a strong urge to move the legs, and the relief with movement may ultimately reveal a pathophysiology similar to that of akathisia. The response to dopaminergic agents and the association with ADHD indicate that RLS is associated with dopaminergic dysfunction. Most patients with RLS have periodic limb movement disorder in sleep (PLMS). The pediatric population with RLS often experiences inattention, overactivity, and mood lability from the associated disruption or fragmentation of sleep.

According to DSM-5, the urge to move the legs must also include all of the following: begins/worsens during periods of rest or inactivity, partially or totally relieved by movement, and is worse in the evening or at night than during the day. The symptoms can delay sleep onset and awaken the individual from sleep. Onset of RLS is usually in the second or third decade of life.

Diagnosis in children may be challenging because children have difficult reporting an "urge." Children and adolescents also report restlessness during the day from prolonged sitting, so a reported increase in restless at night is key to diagnosis. The International Restless Legs Syndrome Study Group published a detailed review regarding the difficulty of diagnosing RLS in the pediatric population.[9] They highlighted the need to rule out common mimics such as positional discomfort, sore leg muscles, sprains/strains, positional ischemia, dermatitis, bruises, and growing pains.

RLS may be precipitated by iron deficiency and/or genetic risk. Several genetic markers have been identified to be associated with RLS. African Americans and Asians appear to be less at risk. Serotonergic antidepressants can induce or aggravate RLS.

Other DSM-5 sleep disorders that are not discussed here include Substance/Medication-Induced Sleep Disorder, Other Specified Insomnia Disorder, Unspecified Insomnia Disorder, Other Specified Hypersomnolence Disorder, Unspecified Hypersomnolence Disorder, Other Specified Sleep-Wake Disorder, and Unspecified Sleep-Wake Disorder

Non-DSM-5 diagnoses

Periodic limb movement in sleep

Periodic limb movement in sleep (PLMS) is more prominent in NREM stage 1 and 2 sleep. PLMS is strongly associated with ADHD and restless legs syndrome (RLS) in the pediatric population. The response to dopaminergic agents and the association with ADHD suggest that PLMS may be related to dopaminergic dysfunction. Characteristic movements may aid in further understanding of the pathology of PLMS.

PLMS presents as repetitive flexion of lower extremities (more common) or upper extremities in youths; movements last for 0.5–5 seconds and occur 5–90 seconds apart. Repetitive jerks are associated with frequent awakenings and daytime somnolence or insomnia. The pediatric population with PLMS often experiences inattention, overactivity, and mood lability as a result of associated sleep disruption or fragmentation. PLMS can occur without RLS.

Limit-setting sleep disorder

Limit-setting sleep disorder is a parent-child transactional model with potentially numerous biopsychosocial variables that influence interactions. It is not simply a failure to set limits; it has a more complex pathogenesis and, ultimately, pathophysiology. Children with limit-setting sleep disorder resist or refuse to go to bed at an appropriate time. Limit-setting sleep disorder may be related to underlying pathophysiology, as is observed in ADHD and other neurodevelopmental disorders, or may be a combined medical-behavioral issue.

Insufficient sleep syndrome

Insufficient sleep syndrome is a condition of chronic sleep deprivation without an underlying disease process. Youths with this syndrome may experience an increased need for sleep during puberty and adolescence.

Insufficient sleep syndrome may represent a poor compensatory ability for sleep loss and includes failure to adequately synchronize sleep-wake behaviors and adapt to environmental demands, such as school. Patients with this syndrome attempt to decrease sleep debt incurred during the week by sleeping later on the weekends.

Surveys report that 20–25% of youths have some type of sleep problem. The following are commonly reported in children aged 2–15 years:

• Nightmares (30%) are more common in younger youths

• Sleepwalking with at least more than 1 episode occurs in 25–30% of youths and is most common in children aged 3–10 years

• Insomnia occurs in 23% of youths

• Enuresis rates decrease from 8% in children aged 4 years to 4% in children aged 10 years

• Bruxism is reported in 10% of youths and may occur in people of any age

• Grinding and clenching teeth at night is reported in 5–8% of adults

• Sleep rocking or head banging is reported in 5% of youths, with head banging being common in infants and in children aged 9 months to 12 years

• OSAS is the most common reason for sleep laboratory referral and affects an estimated 1 to 4% of children[8]

• Narcolepsy (0.01–0.20%) may be underestimated in children because a classic tetrad of symptoms is uncommon in this age group; only about 10% of children show all the symptoms: excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis; semipurposeful automatic behavior, disrupted nocturnal sleep, sudden onset of weight gain, obstructive sleep apnea, and, especially, anosmia, should increase clinical suspicion[10]

• Bedtime resistance in school-aged children has been reported at 15% and is often associated with limit-setting disorder

The results of a population-based study on schoolchildren in Istanbul found that decreased total sleep duration is more prevalent in boys, older children, and children with higher socioeconomic status; insufficient sleep in these groups may be associated with negative behavioral symptoms and sleep hygiene[11]

Restless legs syndrome (RLS) affects 2 to 4% of school-aged children and adolescents.[9]

Race-related demographics

Specific racial risk factors may predispose certain individuals to a sleep-wake disorder. African Americans present more often with narcolepsy without cataplexy or with atypical cataplexy. They may be more prone to having advanced sleep phase–type sleep disorder because of having a shorter circadian period and larger magnitude of phase advances to light than whites. Asian Americans may be at increased risk of obstructive sleep apnea hypopnea despite having low body mass index (BMI).

Sex-related demographics

Sex differences in sleep-wake disorders may be associated with sex roles and/or hormonal changes. Insomnia is more common in females and onset is more likely with the birth of a child or with menopause. During the first few years after menarche, females may experience menses associated periodic hypersomnia. In assessing narcolepsy, females may report fatigue instead of sleepiness and underreport snoring.

During NREM sleep arousal disorders, females are more likely to have eating behaviors. During childhood, sleepwalking occurs more often in females but sleep terrors are more common in males. In contrast, in adulthood, sleepwalking occurs more often in males but the sex ratio for sleep terrors is even. Adult females report having nightmares more often than males.

RLS is more common in females without diagnostic differences. The prevalence of RLS during pregnancy is 2–3 times greater than in the general population. It peaks during the third trimester and improves/resolves after delivery. Nulliparous (never pregnant) females are at the same risk for RLS as males. OSAS is, in contrast, more common in boys.[8]

Learning difficulties, emotional lability, attention deficits, disruptive behaviors, social and school impairments, family dysfunction, low self-esteem, depression, anxiety, cognitive dysfunction hyperactivity, irritability, and memory impairment represent common comorbidities of sleep disorders in children and often exert bidirectional or reciprocal influences. OSAS may lead to cor pulmonale, pulmonary hypertension, right-side heart failure, growth retardation, and failure to thrive.

The treatment of primary insomnia often is difficult. Associated anxiety is often responsive to psychotherapy. Narcolepsy is a lifelong illness. Cataplexy, hypnagogic hallucinations, and sleep paralysis may diminish in frequency over time.

Tonsillectomy and adenoidectomy relieve symptoms in about 70% of pediatric patients with OSAS. Continuous positive airway pressure (CPAP) is indicated for patients who partially respond to surgery or in whom surgery is contraindicated. A review of available treatments for OSAS in children revealed only a limited evidence base to support their use. Extremely limited data from randomized controlled trials are available to support the effectiveness of adenotonsillectomy, although this represents the current quasi-standard and first-line treatment for OSAS.

The success of therapy for delayed sleep phase syndrome (DSPS) depends to a large extent on the adolescent’s level of motivation. To prevent relapse of DSPS, the new schedule must be rigidly maintained.

Most children with parasomnias outgrow this condition when younger than 10 years or demonstrate a progressive decrease to a prevalence comparable to that of the adult population. Approximately 88% of all enuretic children outgrow this condition by the time they are aged 13 years. The prevalence of enuresis in patients aged 13 years is 2%, which is similar to the prevalence rate in the adult population.

For sleep disorder related to a general medical condition, the prognosis depends on treatment of the underlying condition. For sleep disorder related to substance use, prognosis depends on treatment of the addiction.

Because human beings spend a third of their time sleeping, it is essential to emphasize the need for good sleep hygiene to children, adolescents, and their families. Treatment of any behavioral problems generally will not not help unless sleep problems are addressed. "Catch-up sleep" is  a misconception as more studies demonstrate the long-term effects of sleep deprivation. Sleep hygiene includes the following:

• Keeping the room quiet, dark, and comfortable

• Practicing a simple bedtime ritual that includes voiding

• Limiting time spent in bed

• Not eating or drinking heavily for about 3 hours before bedtime

• Maintaining the bedroom for sleeping only

• Removing distractions, such as television

• Avoiding medications

• Considering the effect of sleep partners (including pets)

• Maintaining a consistent sleep schedule

• Avoiding naps

• Exercising regularly

• Taking a hot bath or drinking something warm before bedtime

For patient education resources, see the Sleep Disorders Center, as well as Disorders That Disrupt Sleep (Parasomnias), Night Terrors, Narcolepsy, REM Sleep Behavior Disorder, Periodic Limb Movement Disorder, and Sleeplessness and Circadian Rhythm Disorder.

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR) divided sleep disorders into the following 4 broad categories[2] : Primary sleep disorders, sleep disorders due to a general medical condition, sleep disorders related to another mental disorder, and substance-induced sleep disorders. As noted earlier, the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) has eliminated these delineations to further the understanding that most sleep disorders are complex interactions of behavior and biology.[3] In some ways, DSM-5 oversimplifies the diagnoses of sleep disorders, but this enables the general practitioner to make the diagnoses more reliably.

Sleep disorders are better understood when subdivided into dyssomnias, which are characterized by abnormalities in the amount, quality, or timing of sleep, versus parasomnias, which are characterized by abnormal behavioral or physiologic events that occur in association with sleep stages or sleep-wake transitions.

In evaluating a child or adolescent for a sleep disorder, the importance of a thorough sleep history cannot be overemphasized. A sleep diary, usually kept for about 2 weeks, provides information on night-to-night variability over time. An example of a sleep diary appropriate for children can be found at www.sleepforkids.org/pdf/SleepDiary.pdf.

Self-report sleep questionnaires, such as the School Sleep Habits Survey and the Children’s Sleep Habits Questionnaire (CSHQ), are specific to adolescents and school-aged children, respectively. The Sleep Disturbance Scale for Children (SDSC) is a 26-item parent questionnaire for children and adolescents to screen for primary sleep disorders such as obstructive sleep apnea.

Rating scales can help track patient compliance with behavioral interventions and response to treatment. Rating scales have been developed to quantify subjective sleepiness of patients. The Epstein Sleepiness Scale and the Stanford Sleepiness Scale are examples.

Issues to be addressed in the history include the following:

• Temporal history

• When the problem began

• Predisposing, precipitating, and perpetuating factors

• Review of evening activities and bedtime rituals

• Sleep environment

• Latency to sleep onset

• Arousals - When, for how long, and how often arousal occurs; behavior during awakening; and ease with which the child returns to sleep

• History of snoring, breathing pauses, sleepwalking, talking, enuresis, and nocturia

• Sleep position

• Nightmares and sleep terrors

• Seizure symptoms - Tongue biting, chewing, blood on bedclothes, and encopresis

• Time of morning awakening, sleep paralysis, and early-morning headache

• Total sleep time

• Restorative sleep

• Daytime sleepiness, fatigue, and school performance

• Questions about depression, anxiety, worries or concerns, hyperactivity, and irritability

• Frequency and duration of naps

• Existing comorbid disorders

• Substance use

• Use of caffeine, alcohol, drugs, medications (prescription or over-the-counter [OTC]), and herbal preparations

• Family history of sleep disorder or metabolic disorder

• Parents’ sleep habits[12]

• Efforts made to control symptoms

• Overall impact of sleep disturbance on family

Primary sleep disorders

Insomnia

Insomnia is defined as the subjective symptom of inadequate sleep quantity and quality. Patients with insomnia report difficulty falling asleep or maintaining sleep. Chronic insomnia may produce poor concentration and a low level of energy. Other symptoms include a decreased sensation of well-being and poor productivity. Some patients with primary insomnia feel that the sleep was not restorative. Distress due to inability to sleep may lead to a vicious cycle of frustration and insomnia.

Patients with hypersomnia require more sleep despite long and good sleep (about 12 hours), usually require naps in the daytime, and are not refreshed by short naps.

Patients with narcolepsy may experience the following:

• Excessive daytime sleepiness with irresistible daytime sleep attacks

• Sleep paralysis, in which the individual awakens unable to move

• Cataplexy: May be subtle initially (eg, wobbly knees or dizziness) but may progress to sudden falls following a strongly experienced emotion; children uniquely may experience grimacing or jaw opening with tongue thrusting ("cataplectic faces"); during cataplexy, reflexes are absent even though the attacks usually last less than 10 seconds

• Hypnagogic hallucinations

• Feeling of refreshment after a sleep attack

• Low cerebrospinal levels of hypocretin-1 occur without cataplexy in youths who develop cataplexy later

• Nocturnal eating may occur with increased frequency of obesity

Children with obstructive sleep apnea syndrome (OSAS) have a history significant for loud snoring, breathing pauses, mouth breathing, restless sleep, and increased perspiration at night. Snoring is the most common presenting symptom. Hyperactivity and failure to thrive are common symptoms of childhood obstructive apnea.

Other symptoms in children with OSAS include excessive daytime sleepiness, morning headaches, and behavioral changes (paradoxical hyperactivity as children try to stay awake). These children also experience emotional lability, changes in school performance, and, eventually, cardiac failure.

Of the circadian rhythm sleep disorders, delayed sleep phase syndrome (DSPS) is the most common, with a prevalence of about 7% among adolescents. It is characterized by early insomnia, little or no difficulty maintaining sleep, and difficulty waking in the morning.

Parasomnias

Nightmare disorder affects 10–50% of children aged 3–6 years. Nightmares occur during rapid eye movement (REM) sleep, usually in the second half of the night, and are well remembered in the morning. After a nightmare, the child is alert and can clearly describe scenes and frightening images in detail.

Nightmares are common during stressful times or after frightening events, such as frightening movies. If nightmares are severe and frequent, they may affect daytime functioning. In posttraumatic stress disorder (PTSD), nightmares may be associated with flashbacks, numbing, reenacting the events, and avoidance.

Night terrors, also known as sleep terrors, typically occur in the first 3 hours of sleep. The child is not awake but appears agitated. Abrupt, usually agitated, arousal from slow-wave sleep takes place. Night terrors are associated with autonomic arousal (eg, tachypnea, tachycardia, and diaphoresis) and screaming. The child is often inconsolable during the episode. After about 3–5 minutes, the episode terminates spontaneously, and the child quickly returns to sleep. Recall of the event in the morning is poor. This type of disturbance may be associated with an ongoing illness or fever.

In sleepwalking disorder (somnambulism), the patient is difficult to arouse and usually has no recollection of the event in the morning. Actions taking place during sleepwalking frequently vary. Sleep eating occurs more frequently in females.

In primary nocturnal enuresis (bed wetting), no period of nighttime dryness occurs for more than 6 months. In secondary enuresis, a relapse of bed wetting occurs after a period of at least 6 months of dryness. This sleep disturbance may be associated with shame and low self-esteem and therefore should prompt a review for other psychiatric disorders. Secondary enuresis may be precipitated by emotional and physical trauma.

Sleep disorders related to general medical condition

A wide variety of medical and psychiatric disorders may result in sleep disruption. The clinician should establish the presence of a general medical condition, but it is not necessary for the diagnosis of sleep-wake disorder in DSM-5. The clinician should consider how, the sleep disturbance is causally related to the medical illness through a physiologic mechanism to help clarify treatment. For example, cluster headaches occur more frequently during the night than in the daytime. Sleep-related headaches usually awaken the patient and fragment sleep. Blind individuals experience cyclic disorders because of the lack of cues that continually reset the internal clock to fit the 24-hour day-night cycle.

In pediatric populations, epilepsies occurring during sleep account for 30% of seizure disorders. Epilepsy appears to fragment sleep and causes impairment in daytime functioning.[13] The sleep disturbances associated with developmental central nervous system (CNS) disorders generally reflect fragmentation with frequent awakenings, difficulty in initiating sleep, and early morning awakenings. 

Kleine-Levin syndrome or periodic hypersomnia comprises a constellation of symptoms that include episodes of excessive somnolence, overeating, and sexual disinhibition; it is 4 times more frequent in boys than in girls.[14] Behavioral disturbances, such as irritability and confusion, are associated with this syndrome, and occasional hallucinations have been reported. Derealization, a dream-like state or experiencing life outside their own bodies, is often present. A significant number of patients have had a complicated birth history and some developmental delay.

Symptoms of Kleine-Levin syndrome typically begin during adolescence, median age of onset is 15 years, either gradually or abruptly. Onset follows a flulike illness or injury with loss of consciousness in half the cases. The course of the syndrome is characterized by remissions and relapses, with relapses occurring at intervals of weeks to months. Symptoms may last from days to weeks. Kleine-Levin syndrome usually resolves spontaneously during late adolescence or early adulthood. The etiology of Kleine-Levin syndrome is unknown. The majority of individuals have slowing of their EEG during an episode. Imaging studies, cerebrospinal fluid analysis, and MLST are usually normal.

Paradoxical hyperactivity in children with attention deficit hyperactivity disorder (ADHD) encourages them to stay awake. Emotional lability may be observed. Children with ADHD tend to have fewer and shorter arousals than adults. They also tend to have obstructive hypopnea (transient reduction of airflow that lasts at least 10 seconds), with relatively few complete apneic (breathing stops for >10 seconds during sleep) events. Children with ADHD have a strong tendency to fall asleep during the day. They have high rates of restless legs syndrome (RLS) and periodic limb movement in sleep (PLMS) and a higher prevalence of OSAS.

Sleep-disordered breathing and PLMS have been frequently found in children with ADHD who have symptoms and complaints of disturbed sleep. Routine assessment of the sleep habits of patients with ADHD is important; consider objective sleep assessment, including polysomnography (PSG).

Approximately 50% of children with Tourette syndrome have sleep disturbances. Nocturnal awakenings and movements increase when tics persist into sleep. Comorbidity exists with obsessive-compulsive signs, traits associated with increased sleep latency, decreased REM sleep, and deceased REM sleep latency. Children and adolescents with this movement disorder are at risk for parasomnias. Patients with Tourette syndrome have a higher incidence of enuresis. Tourette syndrome is associated with prolonged sleep latency. Short and fragmented sleep results in low sleep efficiency.

In Down syndrome or Trisomy 21, airway hypotonia leads to obstructive apnea that is not associated with obesity, age, or congenital heart disease. Central apnea also is common and is associated with significant oxygen desaturation. These individuals are also at greater risk for early hypothyroidism, which contributes to disrupted sleep.

In Prader-Willi syndrome, obesity, hyperphagia, and developmental delay are the most common features. Prader-Willi syndrome develops when a segment of the paternal chromosome 15 is deleted. Obesity can cause obstructive sleep apnea. An increased frequency of apneas, a decreased nadir of oxygen saturation, an increased maximum heart rate, and a blunted respiratory response to hypercapnia during non-REM (NREM) sleep all may occur in patients with Prader-Willi syndrome. Sleep time and slow-wave sleep increase during the day and at night. Upper airway resistance syndrome results in REM fragmentation and extra daytime sleep (EDS).

Individuals with Smith-Magenis syndrome have severe disrupted sleep patterns, which begin early in life. This disorder is caused by the deletion of a small piece of chromosome 17. Neurobehavioral abnormalities also include aggressive and self-injurious behavior. Children may be very sleepy during the day, have trouble falling asleep, and awaken several times each night. These sleep disturbances are correlated with disturbed circadian rhythm in melatonin levels. The chromosome delete results in the absence of the RAI1 protein. This protein appears to control the expression of several genes involved in circadian rhythm.[15]

Menstrual-associated periodic hypersomnia is another cyclic sleep disorder, noted during the first few years after menarche. Attacks generally last 1–2 weeks after ovulation, with sudden resolution occurring at the time of menses. Pregnancy is associated with increased risk for RLS.

Sleep-related gastroesophageal reflux disease (GERD) is characterized by regurgitation of stomach contents into the esophagus during sleep. It is very common in patients using theophylline as a respiratory stimulant for apnea of prematurity or asthma. Theophylline is a prescribed medication related to caffeine. Nighttime exacerbations of childhood asthma are common and may lead to significant sleep disruption.

Children with atopic dermatitis tend to have increased sleep-onset difficulty, night awakenings, and decreased sleep duration as a result of pruritus and medications, such as antihistamines and corticosteroids. Children with chronic illnesses, such as juvenile rheumatoid arthritis (JRA) or sickle cell disease, can experience sleep difficulties. Treatment of the primary disorder does not necessarily improve the sleep issues.

Sleep disorders related to another mental disorder

Insomnia related to another mental disorder is common (35–50%) among individuals who present to sleep disorder facilities for evaluation of chronic insomnia. In young children, separation anxiety, stress, and trauma may result in nighttime awakening, nightmares, or resistance to going to bed. Sleep disruption is usually part of the diagnostic criteria for a psychiatric disorder.

Patients who have major depressive disorder or dysthymic disorder often report difficulty in falling asleep or staying asleep or early morning awakening with inability to return to sleep. Hypersomnia can be a feature of depression, especially major depression with atypical features. Children and adolescents with major depressive disorder generally present with less subjective sleep disturbance and fewer PSG changes than do older adults with a similar degree of depression.

Prepubertal children with depression are more likely to experience insomnia (75%) than hypersomnia (25%); after puberty, hypersomnia predominates. Hypersomnia is a common feature of depressive disorders in adolescents and young adults. Insomnia is more common in older adults.

Individuals with generalized anxiety disorder and posttraumatic stress disorder report difficulty in falling asleep and may awaken with anxious thoughts in the middle of the night. Panic attacks can arouse patients and cause insomnia. Significant insomnia is observed during exacerbations of schizophrenia and other psychotic disorders but rarely is a predominant symptom. Children with psychotic symptoms may be too afraid to get out of bed to use the bathroom and therefore present with secondary enuresis. Other mental disorders that may be related to insomnia include adjustment disorders, somatoform disorders, and personality disorders.

Substance-induced sleep disorders

Substance-induced sleep disorder most commonly occurs during intoxication with substances such as alcohol, amphetamine and related substances, caffeine, cocaine, opioids and sedatives, hypnotics, or anxiolytics. Substance-induced sleep disorder can also occur in association with withdrawal from these same classes of substances. Patients may report that the substance is used to trreat a primary sleep disorder.

Diagnostic criteria for substance-induced sleep disorder include the following:

• Prominent disturbance in sleep that is sufficiently severe to warrant independent clinical attention

• Evidence from the history, physical examination, or laboratory findings of both (1) symptoms that developed during or soon after substance intoxication or withdrawal and (2) medication use that is etiologically related to the sleep disturbance

• Disturbance that is not better accounted for by a sleep disorder that is not substance induced or occurs exclusively during the course of delirium.

Evidence that the symptoms are better accounted for by a sleep disorder that is not substance induced might include the following:

• Symptoms preceding the onset of the substance use (or medication use).

• Symptoms persisting for a substantial period (eg, about 1 month) after the cessation of acute withdrawal or severe intoxication

• Symptoms that are substantially in excess of what would be expected from the type or amount of the substance used or the duration of use, or the presence of other evidence suggesting an independent non–substance-induced sleep disorder

Alcohol-induced sleep disorder typically occurs as the insomnia type. Alcohol, which often facilitates sleep onset, can lead to decreased REM sleep and sleep disruption. Acute intoxication initially results in increased sleepiness and reduced wakefulness for 3–4 hours.

An increase in stages 3 and 4 of NREM sleep is a typical feature of this initial stage. After these initial effects, the individual experiences increased wakefulness, restless sleep, and, often, vivid and anxiety-laden dreams during the second half of the night. In addition, alcohol can increase the number of obstructive sleep apnea events and result in fragmented sleep. With continued habitual use, alcohol continues to show a short-lived sedative effect for several hours, followed by sleep continuity disruption for several hours.

During alcohol withdrawal, sleep architecture is grossly disturbed. Sleep tends to be fragmented and accompanied by an increase in the amount and intensity of REM sleep. Vivid dreams often accompany this stage of sleep.

During the period of acute intoxication, amphetamines produce sleep disruption associated with increased sleep latency, reduced total sleep time, fragmented sleep, an increase in body movements, and a decrease in REM sleep. Slow-wave sleep tends to be reduced. During withdrawal from long-term amphetamine use, hypersomnia with prolonged nocturnal sleep duration and excessive daytime sleepiness tends to be the rule.

Caffeine-induced sleep disorder is characterized by insomnia during intoxication and by hypersomnia and excessive daytime sleepiness during withdrawal. Caffeine is known to result in increased wakefulness and sleep fragmentation, which may be documented on PSG as prolonged sleep latency, multiple arousals, and a decrease in slow-wave sleep. Lack of awareness of the long half-life of caffeine and its metabolities, up to 15 hours, contribute to this disorder. As discussed earlier, caffeine-related products contribute to esophageal reflux, which can disrupt sleep.

Short-term use of opioids produces increased sleepiness and reduced REM sleep. Insomnia and frequent arousals become common with prolonged use. Opioid withdrawal generally produces symptoms and signs of CNS hyperactivity, though some patients may report hypersomnia.

Use of sedative-hypnotic medications produces an increase in sleepiness and PSG findings of decreased REM sleep and an increase in sleep-spindle activity. On the other hand, long-term use of sedatives may be accompanied by symptoms of insomnia and tolerance to these medications. Patients may be reluctant to discontinue use of these medications even though insomnia has relapsed due to perceived benefit for anxiety.

Withdrawal from sedative-hypnotics and anxiolytics is associated with anxiety and insomnia. The manifestation of withdrawal symptoms depends on the half-life of the drug used. Withdrawal from drugs with short half-lives typically produces insomnia. Medications with long half-lives are associated with symptoms of excessive sedation during their use.

Heavy adult users of cannabis have reduced REM and slow wave sleep (SWS), increased sleep latency, and increased vulnerability to sleep deprivation effects. During abstinence, there are PSG changes.[16] Cannabis use in adolescents is on the decline but may increase with states legalizing it for medicinal and recreational purposes. Adolescents who use cannabis show functional decline in sleep quality, with similar changes in sleep as those seen in adult users.[17] Adult users of cannabis often have early-morning sleepiness, which would exacerbate the common problem of adolescent daytime sleepiness during the first 2 periods of school.

A full physical examination, focusing on the causes and consequences of sleep-related disorders, is warranted. Significant things to look for in a physical examination include the following:

• Level of consciousness - extremely atypical for elementary school children to be somnolent in the office

• Physical features - head circumference, weight and indicators of failure to thrive, features suggestive of congenital anomalies, and size of the posterior pharynx

• Physical causes of airway blockage (eg, enlarged tonsils or adenoids)

• Obesity and neck circumference

• Systemic signs of heart failure (eg, clubbing or cyanosis)

• Signs indicative of seizure activity

• Tooth injuries on tongue

• Incontinence

• Postictal changes in sensorium

The physiological and behavioral complications of sleep deprivation are enduring and have significant impact on academic success and quality of life for the child and their family. Early treatment success will minimize these complications. Even with adequate treatment of sleep apnea, neurons may be permanently damaged and additional treatment of daytime sleepiness is needed. Treatment for these complications is needed as part of the overall management of sleep disorders. 

Sleep laboratory studies are very helpful when indicated, but most common pediatric sleep problems do not require formal sleep laboratory testing. Most sleep problems resolve with behavioral treatments. Overnight polysomnography (PSG) and next-day multiple sleep latency tests (MSLTs) represent the most commonly used sleep studies. Clinical suspicion of any of the following disorders should prompt referral for sleep studies:

• Sleep-related seizurelike activity

• Sleep-related gastroesophageal reflux

• Nighttime asthma or persistent cough

• Attention deficit hyperactivity disorder (ADHD)[18] or Tourette syndrome associated with restless sleep and disrupted daytime functioning

• Restless legs syndrome (RLS) and periodic limb movement during sleep (PLMS) – Both are relatively common in these patients

• Recurrent rapid eye movement (REM) sleep behaviors

• Severe bruxism

• Snoring and hypopnea or apnea

• Recalcitrant or unexplained and daytime somnolence

• Suspected narcolepsy

MSLTs aid in clarifying unexplained excessive daytime sleepiness and narcolepsy symptoms but must be performed after the individual has stopped all psychotropic medications and has 2 weeks of sufficient sleep time.

Practice parameters for PSG and MSLT testing in children are based on the strength of evidence for respiratory[19] and nonrespiratory indications.[4] The articles define the "standard" recommendation as being generally accepted patient-care strategy based on overwhelming prospective studies and/or well-designed retrospective studies. "Guideline" recommendations are based on moderate clinical certainty, some number of well-controlled prospective and/or well-designed retrospective studies or a consensus of retrospective studies. The "option" recommendation reflects uncertain clinical use and inconclusive/conflicting evidence or expert opinion.

For respiratory indications, PSG is a standard indication for obstructive sleep apnea evaluation, following adenotonsillectomy for obstructive sleep apnea syndrome (OSAS), craniofacial anomalies that disrupt the upper airway, and neurological disorders (trisomy 21, Prader-Willi syndrome, and myelomeningocele). PSG should be standard in the titration of positive airway pressure in OSAS. Guideline recommendations are present for use of PSG in the assessment of congenital central alveolar hypoventilation syndrome, sleep-related hypoventilation related to neuromuscular disorders or chest wall deformities, and selected cases of primary sleep apnea of infancy. In infants with clinical evidence of sleep-related breathing disorder, PSG is a guideline recommendation for those with an apparent life-threatening event. In children being considered for adenotonsillectomy to treat obstructive sleep apnea, PSG is also only a guideline recommendation.

For nonrespiratory indications, standard use of PSG is indicated in children suspected of having periodic limb movement disorder (or RLS). MSLT preceded by nocturnal PSG is indicated for children being evaluated for narcolepsy. In children with non-REM (NREM) parasomnias, epilepsy, or nocturnal enuresis, PSG is a guideline recommendation if there is suspicion of sleep-disordered breathing or periodic limb movement disorder. MSLT preceded by nocturnal PSG is an option in children suspected of having hypersomnia for causes other than narcolepsy. PSG with an expanded EEG montage is an option in children to confirm a diagnosis of an atypical or potentially injurious parasomnia or to differentiate parasomnia from sleep-related epilepsy. PSG is an option for evaluating children suspected of having RLS.

Routine dipstick urinalysis, growth/height trajectory, and blood pressure are used to exclude other medical causes of enuresis. Lumbar puncture to measure hypocretin and genetic testing may be helpful for diagnosing narcolepsy.

This section primarily reviews forms of cognitive-behavioral therapy (CBT) that are effective in treating a broad range of childhood behavioral sleep problems. Treatment modalities can be adapted easily to the youth’s developmental level and should consider the role of sleep hygiene in all sleep problems. The effectiveness of CBT for childhood sleep disorders has been well demonstrated in controlled studies and clinical case reports.

Pharmacologic treatments of sleep disorders are not supported by adequate and significant empiric data. Given the lack of supporting data, it is advisable to employ behavioral and cognitive strategies initially in most cases. Because of the paucity of adequate empirical studies, pharmacotherapy data are limited to treatment in select sleep disorders.

Adenotonsillectomy may be indicated for obstructive sleep apnea syndrome (OSAS). Weight loss is recommended for patients with obesity and OSAS.

Specific interventions for sleep problems have gained the status of established evidence-based interventions. The issues that received the most attention pertain to settling problems and night awakenings in infants and toddlers. These topics have been extensively studied, with an impressive volume of well-controlled and informative clinical studies. Clinical research of all other sleep problems and in other age ranges is still very limited.

Family dynamics should be explored and redressed. Sleep patterns of parents and their adolescent children reveal similarities[12] ; for example, strained and reciprocal parent-child interactions indicate that a mother’s poor sleep may directly affect parenting style. Accordingly, adolescents’ psychological functioning and sleep are also affected.

Limit-setting problems, bedtime resistance, and frequent nightly awakenings represent common problems encountered in pediatric practice. CBT uses relatively straightforward and safe strategies for enhancing overall parenting effectiveness as well as ameliorating the aforementioned problems. Such strategies include the following:

• Extinction technique – This technique involves the parents putting their child to bed at a designated time and ignoring the child’s or infant’s protests until an established time the next morning

• Graduated extinction – Many parents may experience or perceive pure extinction as overly taxing or cruel; therefore, a graduated extinction technique may be used, which may include progressive time delays in responding to bedtime protests or refusals (ie, a checking technique) or may involve comforting for increasingly shorter intervals when checking on the child

• Positive routine-stimulus control technique – This technique involves developing a consistent, pleasurable, and calming nighttime routine, with pleasurable activities being halted if the child protests or throws a tantrum; the child is then put to bed

• Scheduled awakenings – Parents awaken the child approximately 15 minutes before his or her typical nightly awakening times; the scheduled awakenings then are gradually stopped or tapered off

In patients with nocturnal enuresis, the history and physical examination are usually sufficient to rule out a urologic abnormality. If medical causes of enuresis are ruled out, children younger than 6 years should be managed with child and family reassurance that the enuresis is developmentally normal. Older children may benefit from medication to reduce embarassment. Helpful behavioral strategies include the following:

• Alarm clock method – An alarm is set before the most probable time of the event (as suggested by preceding enuretic episodes); the alarm may be set for a predetermined time, such as 2-3 hours after usual onset of enuresis; children eventually avoid wetting themselves before the alarm is triggered (in contrast with the bell and pad method); longer treatment duration results in a higher success rate

• Parent education – Parents need to know that sleep hygiene practices serve as prevention of enuresis; fluid restriction, bedtime voiding, and parent awakening later are components of sleep hygiene (see Patient Education); the earlier the child begins practicing sleep hygiene, the better; individual families may require creative combinations of the aforementioned interventions

Treatment for sleep-related fears and anxiety includes relaxation training, guided imagery, positive self-talk, positive reinforcement for increasingly successful efforts, systematic desensitization, and gradual exposure to a child-determined hierarchy of sleep-related fears or anxiety. The child progresses from envisioning less threatening fears to conquering in vivo actual feared objects or situations. Exposure-response prevention is combined with relaxation techniques and positive reinforcement for treatment gains.

In patients with periodic limb movement during sleep (PLMS) or restless legs syndrome (RLS), CBT should focus alleviating stress and promoting relaxation. Pharmacologic therapy may be considered (see below).

In patients with circadian rhythm disorders, light therapy in the morning can help reset the suprachiasmatic nuclei. The individual is exposed immediately upon awakening to 8,000–10,000 lux of bright light for 20 to 30 minutes.[20] If a light box is used, it is placed at 18 to 24 inches from the face. Chronic use of a light box can lead to development of cataracts. This is the opposite of the effect of melatonin (see below), which can be used at night to help induce sleep. In manipulating the internal sleep-wake clock, gradually delaying sleep onset resynchronizes the internal clock. Sleep onset should be delayed in 3-hour increments each night until the desired sleep time is established.[20]

Pharmacotherapy for insomnia in youth is generally not a permanent intervention. For transient episodes of insomnia, melatonin or antihistamines such as diphenhydramine (Benadryl) have been used clinically with varying degrees of success.

For patients with nocturnal enuresis, desmopressin therapy may be helpful. Individuals with primary enuresis and lack of circadian rhythmicity of plasma arginine vasopressin are more likely to respond to desmopressin therapy. This agent reduces nocturnal urine production, has better short-term results than the alarm method, is effective in 50-85% of individuals, and generally is well tolerated; recidivism after discontinuance can present a problem. Some individuals can experience severe hyponatremia and seizures, which is why the intranasal form of desmopressin has been discontinued. Treatment with desmopressin tablets should be interrupted during episodes of fluid and/or electrolyte imbalance, such as fever, recurrent vomiting or diarrhea, vigorous exercise, or other conditions associated with increased water consumption.

Imipramine therapy has been used historically in the treatment of enuresis; however, it is not a first-line medication, given its potentially serious cardiac adverse effects. This agent (given in a dose of 25-100 mg, depending on the age and size of the patient) may be effective, but there are concerns about potentially serious adverse effects, which often outweigh the benefits in patients with relatively benign problems. Baseline electrocardiography (ECG) is required, with titration and dose increases and periodic monitoring. The clinician should also monitor blood pressure, pulse rate, and review cardiovascular issues at each visit.

For patients with PLMS or RLS, dopaminergic therapy may be necessary; however, only limited data on dopaminergic therapy in youths are available. Pergolide (withdrawn from the US market on March 29, 2007) is effective in treating ADHD or Tourette syndrome and comorbid sleep disorder. Caffeine restriction can be helpful. Low-dose valproic acid has been shown to be effective in a small case series of adults.

A study by Blumer et al found that zolpidem failed to improve insomnia in children and adolescents with ADHD.[21] The hypnotic efficacy of zolpidem was compared with that of placebo in children aged 6-17 years who experienced insomnia associated with ADHD. Patients were randomized to receive either zolpidem (0.25 mg/kg/day, not exceeding 10 mg/day total) or placebo. After 4 weeks of treatment, baseline-adjusted mean change in latency to persistent sleep did not differ significantly between the zolpidem and placebo groups.

In patients with circadian rhythm disorders, melatonin may be used. Melatonin acts directly on suprachiasmatic nuclei (the opposite of the effect of light on phase shifts). Phase delay requires morning dosing of melatonin; advanced sleep phase syndrome requires evening dosing (0.5 to 5 mg about 5 to 5.5 hours before bedtime).[20]  Ramelteon, a melatonin receptor agonist, is a US Food and Drug Administration (FDA)–approved medication for the treatment of insomnia in adults. A new medication, tasimelteon, has been approved by the FDA for the treatment of non–24-hour disorder in totally blind adults. Tasimelteon is also a melatonin receptor agonist.

Other common pharmacologic interventions include central alpha-2 agonists and antihistamines, even though little data support their use. In one recent survey, one third of pediatricians reported using clonidine for sleep onset, nighttime awakening, early morning awakening problems, and parasomnias. Central alpha-2 agonists may decrease nightmares associated with trauma.[22] Antihistamines were the most commonly used medication for treating sleep disorders.[23] In a larger study, physicians also commonly prescribed benzodiazepines 15% and antidepressants (trazodone) 6%.[24]

Adenotonsillectomy is the primary treatment modality in children with OSAS, however recurrence is common post-surgery.[6] Myofunctional therapy in conjuction with orthodontia and craniofacial surgery may be more effective. Tongue and facial muscle exercises improve adult OSAS. Positive airway pressure is needed in cases of continued postoperative symptoms. Continuous positive airway pressure (CPAP), variable pressure devices (eg, bilevel positive airway pressure [BiPAP]), and on-demand pressure when airflow is impeded (D-PAP) may be needed. Weight loss can be helpful for obese patients.

Depending on patient presentation, the following consultations may be necessary:

• Pulmonologist

• Developmental medicine specialist

• Neurologist

• Child psychologist, child psychiatrist, or developmental-behavioral pediatrician

• Sleep specialists – Multiple disciplines may have expertise, and the child may benefit from interdisciplinary evaluation and treatment planning

• Otolaryngologist

• Substance abuse evaluation

School avoidance may develop and result in truancy, especially in adolescence.

Education about the effects of alcohol and caffeine can improve many issues related to insomnia.

Regular exercise improves sleep. For some individuals, exercise 3 to 6 hours before sleep may be helpful.

Anticipatory guidance at well child appointments by primary care providers is the most important preventative measure against developing common sleep disorders. Good sleep habits are correlated with better behavioral health outcomes.[25] To enable clinicians with a busy practice, sleep specialists recommend using the mnemonic “ABCs” of “SLEEPING.”

Age appropriate Bedtimes and waketimes with Consistency

Schedules and routines

Location

Exercise and diet,

no Electronics in the bedroom or before bed

Positivity

Independence when falling asleep

Needs of child met during the day

equal Great sleep.

Regular follow-up is essential to monitor appropriate use of equipment for obstructive sleep apnea, adherence to medications, and for worsening of symptoms or related complications. Cognitive behavioral therapy "refresher" sessions every 3 months to yearly will also help maintain good sleep hygiene strategies.

The goals of pharmacotherapy are to improve sleep maintenance and treat nocturnal enuresis. Many of the medications described below are used 'off-label' and are not approved by the US Food and Drug Administration (FDA) for adolescents and children.

Class Summary

Desmopressin is a synthetic antidiuretic hormone with actions mimicking vasopressin. It is used for treating enuresis.

Desmopressin (DDAVP)

Desmopressin is used to treat primary nocturnal enuresis in children older than 6 years. It increases the cellular permeability of the collecting ducts, resulting in reabsorption of water by the kidneys.

Class Summary

Tricyclic antidepressants are used for treating narcolepsy and enuresis. Scant data exist to support their use in childhood narcolepsy. Sudden death has been reported in 8 children, possibly related to use of imipramine and desipramine; findings have been inconclusive about the causes of these deaths. No FDA indication exists for use of these agents in children with narcolepsy and enuresis.

Imipramine (Tofranil, Tofranil PM)

Imipramine inhibits the reuptake of norepinephrine or serotonin (5-hydroxytryptamine, 5-HT) at the presynaptic neuron. It may be useful for treating pediatric attention deficit hyperactivity disorder (ADHD), as well as enuresis and, possibly, pediatric-onset narcolepsy.

Class Summary

In patients with circadian rhythm disorders, melatonin agonists may be used. Melatonin acts directly on suprachiasmatic nuclei. Use of OTC melatonin in children is recommended to be brief and not to exceed 10 mg per day.[26]

Melatonin

Melatonin is used to treat circadian rhythm disturbances in blind patients without light perception. Use in children is recommended to be brief and not to exceed 10 mg per day. The dose of melatonin will vary depending on the formulation. Over-the-counter forms of melatonin vary in quality and reliability.

Ramelteon (Rozerem)

Ramelteon is a melatonin receptor agonist with high selectivity for human melatonin MT1 and MT2 receptors. MT1 and MT2 are thought to promote sleep and to be involved in maintaining circadian rhythm and normal sleep-wake cycles. Ramelteon is indicated for insomnia in adults characterized by difficulty with sleep onset.

Class Summary

Studies of the use of sedative-hypnotics to treat sleep disorders are limited to adults, and no FDA indications are approved for children younger than 18 years.

Eszopiclone (Lunesta)

Eszopiclone is a nonbenzodiazepine hypnotic pyrrolopyrazine derivative of the cyclopyrrolone class. The precise mechanism of action is unknown but is believed to involve interaction with gamma-aminobutyric acid (GABA) receptors at binding domains close to, or allosterically coupled to, benzodiazepine receptors.

Eszopiclone is indicated for treatment of insomnia in adults by decreasing sleep latency and improving sleep maintenance. It has a short half-life (6 hours). Higher doses (ie, 2 mg for elderly and 3 mg for nonelderly adults) are more effective for sleep maintenance, whereas lower doses (ie, 1 mg for elderly and 2 mg for nonelderly adults) are suitable for treating difficulty in falling asleep.

Class Summary

Valproic acid was efficacious in small case series for adults with RLS and PLMS.

Valproic acid (Depakene, Depakote, Stavzor)

It is likely that all forms of valproic acid have similar efficacy. The following preparations can be used: 250-mg tablet, 125-mg sprinkle capsule, or 250 mg/5 mL liquid (US preparations).

Class Summary

Preliminary efficacious results for treatment using these agents have been noted in youths with restless legs syndrome (RLS) and periodic limb movement during sleep (PLMS). Findings are based on nonrandomized non–placebo-controlled study.

Pergolide was withdrawn from the US market on March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation. Do not abruptly stop pergolide. Health care professionals should assess patients’ need for dopamine agonist therapy and consider alternative treatment. If continued treatment with a dopamine agonist is needed, another such agent should be substituted for pergolide. For more information, see FDA MedWatch Product Safety Alert and Medscape Alerts: Pergolide Withdrawn From US Market.

Pergolide (Permax)

Withdrawn from US market. Pergolide is not FDA-approved for RLS or PLMS. It is a potent and long-acting dopamine agonist that reduces tonic stimulation of dopaminergic D2 receptors located on intrastriatal cholinergic neurons.

clonidine

Antihypertensive used for many decades to treat insomnia in children. Now it is currently approved in extended release form for the treatment of Attention Deficit Hyperactivity Disorder. The benefit of sedation wears off in several weeks but may have continued benefit for reducing nightmares associated with trauma (insert new reference Belkin MR, Schwartz TL. Drugs in Context 2015; 4: 212286. DOI: 10.7573/dic.212286 1 of 5 ISSN: 1740-4398). Main side effects are sedation and dizziness. Duration of effect is usually 2 to 4 hours so may result in nighttime awakening unless extended release is prescribed