BMJ  2006;332:828-832 (8 April), doi:10.1136/bmj.332.7545.828

Clinical review

Sleep disorders in children and adolescents

¹ Sleep Disorders Center, Mayo Clinic, Rochester, MN, USA

Introduction

A recent telephone survey of 1125 adolescents aged 15-18 from France, Great Britain, Germany, and Italy found that about 20% were sleepy in the daytime, 25% had insomnia symptoms, and 4% met established criteria for an insomnia disorder.^{1 2} Sleep-wake disorders are common and have an important impact on the quality of life of children, but if they are promptly recognised and treated the outcome is favourable. Alertness is the inherent ability of the brain to sustain attention and wakefulness with little or no external stimulation;³ sleepiness results from impaired daytime alertness.

Methods

To review issues pertaining to childhood sleep-wake function, we selected Cochrane reviews and key original articles pertaining to sleep neurobiology and childhood sleep-wake disorders, and used our own clinical experience in writing this review.

Mechanisms of sleep-wake regulation

Whether a person is awake or asleep at any given time depends on the net balance between the circadian drive, which facilitates wakefulness, and the homeostatic drive, which facilitates sleep.^4-6

The suprachiasmatic nucleus of the hypothalamus is the circadian timekeeper (biological clock); it receives photic input from the retina and regulates the timing and length of sleep. The hypocretin (orexin) neurons located in the dorsolateral hypothalamus, and their projections to the ventral forebrain and brainstem, serve as the major wakefulness promoting system.

Serum levels of melatonin, a sleep inducing hormone produced by the pineal gland, rise just before sleep onset. Around adolescence, the timing of release of melatonin shifts to a later time at night, rendering teenagers incapable of falling asleep before about 10 30 pm.

Recognising childhood daytime sleepiness

As a general rule in a school age child, habitually falling asleep while travelling in a car or train for less than 30 minutes or while reading or watching television, or regularly napping on return home from school in the afternoon should raise suspicion about pathological daytime sleepiness. Excessive caffeine intake might also be a clue. Box 1 shows important disorders leading to daytime sleepiness, and box 2 lists the neurobehavioural consequences of childhood daytime sleepiness.

Summary points Sleep-wake disorders of diverse aetiology affect about a fifth of children and adolescents and can greatly impact on their quality of life Inadequate sleep hygiene, circadian rhythm disorders, obstructive sleep apnoea, restless legs syndrome, psychiatric disorders, and narcolepsy are most common in this age group The most common causes of childhood obstructive sleep apnoea are adenotonsillar hypertrophy, craniofacial anomalies, and neuromuscular disorders Daytime sleepiness resulting from these conditions may impair concentration, attention span, memory, and behaviour Daytime sleepiness can be managed by adherence to fixed bedtimes and waking times, planned naps, and medications.

Clinical assessment of sleep-wake function in childhood

History taking
Record the time of going to bed, sleep onset time, rituals and habits used for facilitating sleep, presence of habitual snoring, restless sleep, mouth breathing, confusional arousals, sleep walking, sleep terrors, nightmares, bed wetting, whether the patient wakes up tired in the morning, wake-up times on school days and on weekends, daytime naps, drugs used to enhance alertness or to facilitate sleep, whether the patient uses caffeine, nicotine, or other drugs, and how sleepiness impacts on school and social functioning.

Examination
Record height, weight, body mass index, craniofacial anomalies, tonsillar hypertrophy, enlarged tongue base, "adenoid facies," overt sleepiness, labile or depressed mood, inattentiveness.

Sleep laboratory tests
Actigraphy and sleep logs—actigraphy provides longitudinal information about times of sleep onset and wake onset for up to two weeks. It is useful in evaluating insomnia and circadian rhythm disorders (see figure).

View larger version (68K): [in this window] [in a new window]   Wrist actigraph of a patient with delayed sleep phase syndrome. Clear areas indicate diminished muscle activity and correlate with sleep. Note sleep onset (loss of muscle activity) in the early morning hours (5 00 am, 18 July; down arrow) and awakening (bold up arrow) around 12 noon

 

Box 1: Disorders leading to daytime sleepiness in childhood and adolescence Insufficient night sleep and enhanced night-time arousal • Inadequate sleep hygiene: Physical exercise late at night Caffeine misuse Misuse of alcohol, cigarettes, and illicit substances Primary central nervous system disorders Delayed sleep phase syndrome Idiopathic hypersomnia Periodic hypersomnia Narcolepsy—cataplexy, idiopathic Narcolepsy secondary to neoplasms, trauma, inflammatory processes involving the dorsolateral hypothalamus Restless legs syndrome Sleep related breathing disturbance • Obstructive hypoventilation, primary or secondary to Down's syndrome, obesity, hypothyroidism, or myopathies like myotonic dystrophy Drugs Prescription: benzodiazepines, barbiturates, antiepileptic drugs Non-prescription: diphenhydramine, chlorpheneramine, illicit substances Psychiatric • Depression

Nocturnal polysomnography measures multiple physiological variables during sleep. It is indicated when evaluating sleep apnoea and periodic limb movements in sleep, or narcolepsy.

Multiple sleep latency test—four or five planned nap opportunities are provided in a dark, quiet environment. The test measures the speed of falling asleep during the daytime and whether the transition from wakefulness is into REM (rapid eye movement) sleep or non-REM sleep.

Inadequate sleep hygiene

Inadequate sleep hygiene is by far the most common paediatric sleep-wake problem encountered by general practitioners. To begin with, teenagers are unable to fall asleep before 10 30 or 11 pm owing to a physiological shift in the timing of release of melatonin, which usually induces sleep at around 8 30 pm in preadolescence.⁷ Social pressures like after-school sports, evening jobs, television, internet use, mobile phones, and homework may delay bedtime on school nights to between 11 pm and midnight. Caffeine, nicotine, and illicit drugs may also interfere with timely sleep onset. To compound the issue, where school usually starts between 7 15 and 7 45 am students have to awaken by about 6 30 am—yet teens need 9-9.5 hours of sleep to maintain optimum alertness.^{8 9} Most adolescents are thus chronically sleep deprived. Management consists primarily of counselling about sleep hygiene (box 3).

Restless legs syndrome

Restless legs syndrome is an autosomal dominant, sensorimotor disorder characterised by insomnia due to a peculiar "creepy or crawling" feeling in the arms and legs at night, accompanied by an urge to move the limbs.¹⁰ It is exacerbated by keeping the limbs still and is transiently relieved by movement. It interferes with going to sleep and staying asleep and may be accompanied by daytime fatigue, inattentiveness, or frank sleepiness. Restless legs syndrome in childhood is perhaps synonymous with "growing pains."¹¹ In adults, the favourable response of restless legs syndrome to dopamine receptor agonists like pramipexole and ropinorole or to dopamine precursors like carbidopa-levodopa seems to implicate dopamine deficiency in the pathogenesis. Close to two thirds of children with restless legs may have low levels of serum ferritin¹⁰; iron is a cofactor in the synthesis of dopamine. Restless legs syndrome and attention deficit disorder are associated: in a community based questionnaire survey of 866 children aged 2 to 13.9 years, Chervin et al found an odds ratio for significant hyperactivity and restless legs of 1.9.¹² Besides dopamine agonists, oral iron, clonazepam, and gabapentin have also been used to treat restless legs syndrome, but there have been no head to head randomised controlled trials to determine which treatment is most effective.

Narcolepsy

Narcolepsy is characterised by irresistible sleepiness, vivid dreams at sleep onset (hypnagogic hallucinations), momentary paralysis at sleep onset, fragmented night sleep, and abrupt muscle tone atonia triggered by emotions like laughter, fright, or surprise (cataplexy). The cataplectic muscle weakness and atonia last only a few minutes, involve chiefly the extensor muscles, and are associated with absence of muscle stretch reflexes but fully preserved consciousness. The symptoms of narcolepsy result from impaired key arousal mechanisms and the intrusion of REM sleep on to wakefulness. The incidence is highest in the second decade and gradually declines thereafter. About a third of people with narcolepsy have onset before age 15.¹³ The pathogenesis and sleep laboratory diagnostic features are summarised in box 4.

Box 2: Neurobehavioural consequences of daytime sleepiness in childhood Loss of inhibition of the prefrontal cortex, leading to mood swings, impulsivity, and impaired attention and concentration, and increased vulnerability to accidents The ability to convert short term memory into long term memory (consolidation process) is impaired Verbal fluency and complex, divergent, and creative thinking are diminished Use of stimulants like caffeine and nicotine is more likely

General measures for managing narcolepsy, and indeed all daytime sleepiness, are adherence to fixed bedtime and morning wake-up time, and taking one or two planned naps of about 30 minutes each day. Pharmacological treatment of narcolepsy is with modafinil (level I evidence) or with regular or extended release preparations of methylphenidate or dexamphetamine sulfate (dextroamphetamine; level II evidence Cataplexy is treated using clomimipramine, protryptiline, or sodium oxybate ( hydroxybutyrate). Emotional and behavioural problems may require fluoxetine (level II evidence), sertraline, and supportive psychotherapy. Teenagers should not drive if they have uncontrolled sleepiness, and should avoid working in locations where they could endanger themselves or others. Given the autoimmune nature of narcolepsycataplexy, intravenous immunoglobulin at the onset of symptoms may be a novel treatment that warrants further study.¹⁴

Box 3: Sleep hygiene measures for teenagers Go to bed only when sleepy Avoid nicotine Avoid caffeine and heavy exercise within two hours of bedtime as they may delay sleep onset Schedule 30 minutes of "quiet time" before getting into bed—no telephone, radio, television, or computer use Do your worrying before you get into bed, rather than afterwards; write down your worries or your next day's "to do" list onto a note pad that is kept in the bedroom Avoid clock watching at night—it is unnecessary Keep lights low, or off, in the bedroom or toilet at night Try to wake at or about the same time, seven days a week

Psychiatric disorders

Obsessive compulsive disorder, anxiety, depression, and psychophysiological disturbances may lead to insomnia. Substance misuse and drugs like fluoxetine might also play a role.

Delayed sleep phase syndrome

The delayed sleep phase syndrome typically starts in adolescence, mostly in boys. Patients are habitually unable to fall asleep before 2 or 3 am and prefer to wake in the late morning or early afternoon. They show normal sleep quantity and quality when allowed to sleep freely but are very sleepy when they have to conform to more conventional sleep-wake schedules. A higher likelihood of HLA DR1 and the occasional familial clustering of delayed sleep phase syndrome suggest a genetic predisposition. Delayed sleep phase syndrome has been linked to polymorphisms in the hPeriod gene.¹⁵

Box 4: Pathogenesis of narcolepsy-cataplexy Genetic predisposition (presence of the histocompatibility antigen DQB1*0602 in over 95% of patients, compared with a 25-30% prevalence of the antigen in the general population) Acquired stress (head injury, infectious mononucleosis, bereavement, etc) in many cases Degeneration of the hypocretin secreting neurons of the dorsolateral hypothalamus, leading to low to absent hypocretin-1 in the cerebrospinal fluid Impaired alertness and fragmented sleep Intrusion of REM sleep on to wakefulness leads to cataplexy, hypnagogic hallucinations, and sleep paralysis

The condition must, however, be differentiated from school avoidance seen in adolescents with delinquent and antisocial behaviour, as these individuals can indeed fall asleep at an earlier hour at night in the controlled sleep laboratory setting. Maintaining sleep logs and wrist actigraphy (figure) for 1-2 weeks is helpful in establishing the diagnosis.

"Bright light" therapy helps advance the sleep onset time. It consists of providing 2700-10 000 lux of bright light via a light box for 20-30 minutes immediately after waking in the morning. The phototherapy leads to a gradual phase advancement (shifting back) of the sleep onset time at night. Taking 0.5-1 mg melatonin about 5.5 hours before sleep onset also helps in sleep phase advancement. Stimulant drugs can help counter residual daytime sleepiness.

Sleep related breathing disturbance

Sleep disordered breathing is a continuum from primary snoring (snoring without sleep complaints) to frank obstructive sleep apnoea. Obstructive sleep apnoea is characterised by partial upper airway obstruction in the face of preserved thoracic and abdominal respiratory effort. In the United States, it is prevalent in about 2-4% of children, with a higher incidence in those born prematurely or of African-American ethnic origin.¹⁶ The clinical manifestations include habitual snoring, mouth breathing, restless sleep, bed wetting, daytime fatigue, mood swings, and inattentiveness. Adenotonsillar hypertrophy, neuromuscular disorders, and craniofacial abnormalities such as retrognathia, maxillary hypoplasia, and macroglossia are important predisposing factors. Multiple predisposing factors may coexist, as seen in Down's syndrome. Primary snoring has a prevalence of 3-16%; it has been characterised as benign, but lately it too has been linked to neuropsychological impairments.

The upper airway is vulnerable to closure in childhood obstructive sleep apnoea—the mean critical pressure at which the upper airway collapses is higher in children with obstructive sleep apnoea than with primary snoring.¹⁷ The combination of obesity, obstructive sleep apnoea, sleep related hypoventilation with resultant hypercarbia from paradoxical chest and abdominal movement or diminished chest wall excursion, and daytime sleepiness comprise the Pickwickian syndrome. Box 5 shows the consequences of obstructive sleep apnoea.

Unfortunately history alone cannot distinguish obstructive sleep apnoea from primary snoring, which underscores the need for testing in a sleep laboratory. Sleep questionnaires are only marginally better than history taking. Sampling nocturnal oxygen saturation from an oximeter clipped to a finger is a reasonable diagnostic screen. The presence in each hour of sleep of two or more desaturation events of 4% or more and an oxygen saturation nadir below 90% suggest obstructive sleep apnoea.¹⁸ In a prospective study of 110 children undergoing tonsillectomy or adenotonsillectomy, the sensitivity and specificity of oximetry in the diagnosing obstructive sleep apnoea when compared with history and clinical findings were 0.52 and 0.68 respectively (P < 0.05).¹⁹ Abnormal results on overnight oximetry suggest obstructive sleep apnoea, but a normal results do not exclude it.

Box 5: Consequences of childhood obstructive sleep apnoea Central nervous system Sleep fragmentation leads to frontal lobe dysfunction. Animal model studies suggest the developing brain is particularly vulnerable. Cortical microarousals resulting from increased respiratory effort REM sleep and stages III-IV of non-REM sleep are suppressed Inattentiveness, impaired executive function and learning, mood swings, and hyperactivity can result Cardiovascular system Intermittent hypoxaemia causes pulmonary vasoconstriction, which can lead to cor pulmonale. It may also trigger increased sympathetic neural activity, which, if sustained, may alter baroreceptor function. Pulmonary hypertension Cor pulmonale Systemic hypertension Respiratory system Most children maintain normal daytime blood gases and experience hypercapnia intermittently during sleep disordered breathing; this typically resolves with treatment. breathing effort ventilation, O2 saturation Central chemoreceptor reset Metabolism Reduced release of pulsatile growth hormone and raised resting energy expenditure Failure to thrive Impaired glucose tolerance

Nocturnal polysomnography is the gold standard for diagnosing obstructive sleep apnoea and should be considered when oximetry results are equivocal. Nocturnal polysomnography can measure respiratory events and changes in the electroencephalogram due to obstructive sleep apnoea. It is an expensive procedure, and sleep laboratories with equipment and staff geared to the needs of infants and toddlers are not always easily accessible. Nocturnal polysomnography can be bypassed in patients with marked adenotonsillar hypertrophy with classic history of obstructive sleep apnoea: adenotonsillectomy can be done if overnight oximetry is positive, thus conserving sleep laboratory resources for patients in whom the diagnosis is less obvious.

Adenotonsillectomy is the most common treatment for sleep related breathing disturbance. About 20% of patients continue to have symptoms even after surgery; they are likely to be those with underlying craniofacial anomalies, obesity, or neuromuscular or neurological disorders. A therapeutic trial of continuous positive airway pressure breathing is recommended in these patients as it stents the airway and maintains its patency.

A recent Cochrane review of adenotonsillectomy commented on the ongoing debate about the criteria needed to diagnose sleep related breathing disturbance in children.²⁰ There are several reasons for this diagnostic uncertainty. Outdated and relatively insensitive polysomnographic interfaces (like nasal thermocouples or thermistors used for measuring oronasal breathing instead of nasal pressure transducers; mercury filled strain gauges for recording thoracoabdominal effort instead of respiratory inductive plethysmography) impair the detection of sleep related breathing disturbances. A meta-analysis of 12 large studies in which clinical history and examination were correlated with polysomnogram-based diagnosis of obstructive sleep apnoea concluded that the clinical history and examination do not accurately predict childhood obstructive sleep apnoea.²¹ But the meta-analysis was not sufficiently critical—one of the 12 studies had excluded patients with upper airway anomalies and abnormal facial morphology, three studies were retrospective, and three used questionnaire surveys. Prospective studies using reliable, state of the art technology are scarce.

Parasomnias

Parasomnias are undesirable phenomena that intrude on sleep, generally without any daytime consequences. Non-REM sleep parasomnias typically occur in the transition from the deeper into the lighter stages of sleep, about 2-3 hours after initial onset. The child wakes up agitated and confused or walks while asleep, with no recollection of the event the following morning. Most resolve spontaneously over a matter of months. When non-REM parasomnias become problematic, an underlying disorder such as sleep disordered breathing or restless legs syndrome is triggering partial arousals. Low dose clonazepam (0.25-0.5 mg) at bedtime controls most parasomnias. Nightmares are a REM sleep parasomnia and are usually seen in the early morning hours, when REM sleep is more prevalent.

Referral to sleep specialist

When a sleep problem persists despite institution of practical sleep hygiene measures listed in box 4 or when it begins to impact the child's mood, behaviour, and learning, it is appropriate to consider a referral to a sleep specialist (box 6).

Box 6: When should a general practitioner refer a child to a sleep specialist? The child chronically feels unrefreshed on waking up in the morning The school age child finds it difficult to stay awake in the classroom The school age child habitually falls asleep in the classroom or while riding in a car or train for less than half an hour, or naps on returning home from school The child habitually snores The child has difficulty falling asleep or staying asleep through the night that lasts over a month The child has unexplained night time behaviours that keep family members awake

What is on the horizon?

The increasing awareness and prompt treatment of paediatric sleep-wake disorders can enhance the quality of life of children and adolescents. One bottleneck is the limited access to paediatric sleep specialists and sleep diagnostic laboratories. The sleep-related education and training of paediatric postgraduates needs to be enhanced, uniform technical standards for paediatric nocturnal polysomnography need attention, and evidence based guidelines for diagnosis and treatment of specific disorders need development. Genetic aspects of circadian rhythm disorders, narcolepsy, restless legs syndrome, and sleep apnoea syndromes are receiving further study, as are the link between sleep and behaviour and the development of hypocretin analogues for the treatment of narcolepsy.²² This exciting young field seeks to integrate many basic science and clinical disciplines.

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Competing interests: None declared.

Contributors: SK and PP wrote the initial draft; SK revised the paper.

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(Accepted 8 March 2006)

This article has been cited by other articles:

• Hill, C. M, Hogan, A. M, Karmiloff-Smith, A. (2007). To sleep, perchance to enrich learning?. Arch. Dis. Child. 92: 637-643 [Abstract] [Full text]  
• Moore, M., Allison, D., Rosen, C. L. (2006). A review of pediatric nonrespiratory sleep disorders.. Chest 130: 1252-1262 [Abstract] [Full text]  

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