Sleep-Wake Disorders of Childhood

Review Article

Address correspondence to Dr Suresh Kotagal, Department of Neurology and Sleep-Wake Disorders the Center for Sleep Medicine, 200 1st St SW, Mayo Clinic, Rochester, MN 55905, of Childhood [email protected]. Relationship Disclosure: Suresh Kotagal, MD, FAAN Dr Kotagal has received personal compensation as chair of the data safety monitoring board for INC ABSTRACT Research, Inc and receives royalties from UpToDate, Inc. Purpose of Review: Sleep-wake disorders occur in 10% to 28% of children and differ Unlabeled Use of somewhat in pathophysiology and management from sleep-wake disorders in adults. Products/Investigational This article discusses the diagnosis and management of key childhood sleep disorders. Use Disclosure: Recent Findings: The role of sleep in memory consolidation and in the facilitation of Dr Kotagal reports no disclosure. learning has been increasingly recognized, even at the toddler stage. Cataplexy, a key * 2017 American Academy feature of narcolepsy type 1, may be subtle in childhood and characterized by transient of Neurology. muscle weakness isolated to the face. Children with obstructive sleep apnea and restless legs syndrome display prominent neurobehavioral symptoms such as daytime inattentiveness and hyperactivity, so it is important to elicit a sleep history when these symptoms are encountered. Systemic iron deficiency occurs in about two-thirds of children with restless legs syndrome and is easily treatable. Parasomnias arising out of nonYrapid eye movement (REM) sleep, such as confusional arousals and sleepwalking, may be difficult to distinguish from nocturnal seizures, and, in many cases, video-EEG polysomnography is required to differentiate between causes. Summary: Clinicians should routinely integrate the assessment of sleep-wake function into their practices of neurology and child neurology because of the opportunity to improve the quality of life of their patients.

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INTRODUCTION adolescence. This article highlights Pediatric sleep-wake disorders are key issues of pediatric sleep medicine very common. A prospective study that are relevant to both child and followed 359 mother-child pairs from adult neurologists. the birth of the child until 36 months of age and administered surveys about SLEEP ONTOGENY the child’s sleep at 6, 12, 24, and Developmental aspects of sleep regu- 36 months of age; the findings showed lation help us understand the patho- that the prevalence of sleep disorders physiologic aspects of childhood sleep at each assessment point was 10%.1 disorders. The overall quantity of Another large study found that 28% sleep over a 24-hour period and the of children aged 11 to 15 years had temporal organization of various sleep sleep disturbances such as insomnia, stages evolves continuously from in- snoring, or parasomnias.2 Childhood fancy through adolescence. Wakeful- sleep-wake disorders can contribute ness can be differentiated from sleep significantly to behavioral dysregula- by 27 to 28 weeks postconceptional tion and impairment of cognition and age in the preterm infant on the basis learning and differ from sleep prob- of clinical observation and EEG pat- lems in adults because of the continu- terns. At this age, about 80% of total ous neurodevelopmental changes that sleep time is active (rapid eye move- are evolving from infancy through ment [REM]) sleep, characterized by an

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Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINTS irregular respiratory pattern, intermit- ory formation is that 15-month-old h The overall quantity of tent electromyographic activity, and toddlers assimilate new linguistic infor- sleep over a 24-hour low-voltage mixed-frequency EEG activ- mation better if allowed to take a nap period and the temporal ity. By full term (40 weeks post- within 4 hours of presentation of the organization of various conceptional age), active (REM) sleep stimulus, as compared to continued sleep stages evolves decreases to about 50% of the total wakefulness without an ensuing nap.5 continuously from sleep time, with a corresponding in- infancy through crease in the proportion of quiet (non- Shifts in Temporal Organization adolescence. REM) sleep. Sleep spindles and K of Sleep Architecture and Time h Children experience complexes, which reflect maturation of of Sleep Onset large amounts of the N3 thalamocortical activity, appear by 2 to Prior to the age of 3 months, infants sleep stage, which is 3 months of age in full-term infants. By transition from wakefulness directly linked to the release of 4 to 6 months of age after term, non- into REM sleep. After this age, how- growth hormone and REM sleep becomes further differenti- ever, children tend to shift from wake- the consolidation of ated into N1, N2, and N3 sleep stages, fulness into non-REM sleep, with REM explicit memories. which have progressively lighter to sleep occurring 90 to 140 minutes h During transition from deeper arousal thresholds, respectively. after initial sleep onset. Elementary prepuberty to puberty, Sleep stage N3 is characterized by schoolYage children usually become a shift occurs, and melatonin is released at generalized slow-wave activity in the sleepy around 8:00 PM to 8:30 PM. a later time, with a 0.5 Hz to 4 Hz range on EEG. N3 During the transition from prepuberty corresponding delay in (slow-wave) sleep occurs predomi- to puberty, a shift occurs, and melato- sleep-onset time to nantly in the first third of the night. nin is released at a later time, with a 10:30 PM or 11:00 PM. Children experience large amounts of corresponding delay in the sleep- N3 sleep, which is linked to the onset time to 10:30 PM or 11:00 PM, release of growth hormone and the which also correspondingly leads to a consolidation of explicit memories. later shift in the morning wake-up REM sleep decreases progressively time. Also, melatonin secretion de- from the newborn period through clines with advancing Tanner stage ages 3 to 4 years so that by the age during sexual development,6 more so of 3 years, it constitutes only about in boys than girls. When juxtaposed 20% to 25% of total sleep. with early high school start times of The role of sleep in child develop- around 7:30 AM, it is easy to under- ment is underscored by the fact that stand why most teenagers are chron- short-term memories stored in the ically sleep deprived. hippocampus become consolidated into long-term memories in the neo- How Much Sleep Do Children cortex during the N3 sleep stage, at Need? which time a replay of short-term Expert consensus opinions exist regard- memory events occurs. At the electro- ing the amount of sleep children need, physiologic level, this correlates with but there are insufficient recommenda- hippocampal field potential oscilla- tions based on hard data. The widely tions of approximately 180 Hz, which cited opinion of the National Sleep are termed ripples.3,4 Sleep spindles, Foundation,7 shown in Table 11-1, volleys of thalamocortical impulses, provides an approximation of the opti- also play a role in sleep-dependent mum amount of sleep needed. More learning. Both spindles and ripples recently, a panel of experts convened are, in turn, modulated by cortical by the American Academy of Sleep slow waves of approximately 1 Hz. An Medicine also came to approximately example of the role sleep has in mem- the same conclusions concerning

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KEY POINT h approximate sleep-onset time, sensa- Inadequate sleep TABLE 11-1 Approximate Sleep hygiene has become the Requirements at tion of discomfort in the extremities foremost etiology for Various Agesa (restless legs syndrome [RLS]), intru- daytime sleepiness sive thoughts or worries (anxiety), ha- in adolescents. Hours bitual snoring, periods of observed Age of Sleep apnea and restless sleep (obstructive Newborns, 12Y18 hours sleep apnea [OSA]), unusual nighttime 0Y2 months events such as sleepwalking or confu- Infants, 14Y15 hours sion (parasomnias), daytime sleepiness 3Y11 months (hypersomnia disorders), mood distur- Toddlers, 12Y14 hours bances, and medications. 12Y36 months The sleep-related examination should Preschoolers, 11Y13 hours include assessment for height, weight, 3Y5 years body mass index, presence of craniofa- School-age 10Y11 hours cial anomalies, tonsillar hypertrophy and Y children, 5 10 years whether the oral airway is crowded, ex- Teenagers, 8Y9.25 hours amination of the anterior nasal passages, Y 10 17 years andauscultationoftheheartandlungs. a Data from National Sleep Foundation.7 nationalsleepfoundation.org/article/sleep. EXCESSIVE DAYTIME SLEEPINESS hours of sleep needed. This was based Excessive daytime sleepiness in child- upon a review of 864 published articles hood is a frequently overlooked, addressing childhood sleep duration. although common and disabling, symp- Sleeping the recommended hours was tom. The prevalence of excessive day- associated with improved health out- time sleepiness in childhood has been comes, including better attention, be- established based on questionnaire havior, learning, memory, emotional studies. Worldwide, the prevalence of regulation, quality of life, and physical excessive daytime sleepiness in child- and mental health.8 hood and adolescence is estimated at Sleep needs are most likely influenced 4% to 20%.9,10 A detailed sleep-wake by highly individualized determinants, history may help determine a specific including genetic polymorphisms in etiology and formulation of a manage- PER and adenosine receptor genes ment plan. Table 11-2 lists some of the involved in sleep homeostasis and common childhood disorders leading circadian regulation, as well as differing to excessive daytime sleepiness. Only optimal sleep needs for cardiometa- some of the prototypical disorders lead- bolic health, mood regulation, memory ing to excessive daytime sleepiness are consolidation, and learning. Further- discussed in this section. more, the restorative function of sleep may be related both to sleep quantity Inadequate Sleep Hygiene and circadian factors (ie, when, over a Inadequate sleep hygiene has become 24-hour period, we tend to sleep or the foremost etiology for daytime stay awake). sleepiness in adolescents. It is driven by several factors including nocturnal CLINICAL ASSESSMENT mentally activating habits before or The sleep history should inquire into during usual expected bedtime hours, the sleep environment (eg, child’s such as watching television in the 1 to own bed or parents’ bed), bedtime, 2 hours prior to bedtime; playing with

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Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINTS must also be alert toward the possibil- h TABLE 11-2 Causes of The sleep history Excessive Daytime ity of illicit substance use and drug- should determine Sleepiness in seeking behaviors, such as requesting details regarding the Childhood and stimulant medications by fabricating a sleep period, including Adolescence history of sleepiness. Taking afternoon bedtime and when naps in adolescence can also diminish sleep onset occurs for b Circadian Rhythm the drive to fall asleep at night. The both school and Sleep-Wake Disorders use of electronic devices is also a very nonYschool nights. Delayed sleep-wake common contributing problem. h The use of electronic phase disorder The management for inadequate devices is a very Irregular sleep-wake sleep hygiene consists of identifying common contributing rhythms the offending stimulus via the sleep problem to inadequate Non-24-hour sleep cycles history and educating the patient and sleep hygiene. b Environmental his or her parents toward corrective h The salient features of Illicit substances behaviors. Urine toxicology screens Kleine-Levin syndrome Inadequate sleep hygiene are indicated when drug diversion or include periods of Over-the-counter medicines abuse is suspected. Both the patient hypersomnia, inertia, (eg, diphenhydramine) and parents need to be counseled and feelings of Prescription medicines about healthy sleep habits. Mid- to depersonalization. Hyperphagia and b Primary Disorders late-afternoon exercise, as tolerated, of Vigilance hypersexual behavior may facilitate restful sleep at night. occur only in about Idiopathic hypersomnia 50% of patients. Kleine-Levin syndrome Kleine-Levin Syndrome h In Kleine-Levin (periodic hypersomnia) Also referred to as recurrent or periodic syndrome, intercurrent Narcolepsy with cataplexy hypersomnia, Kleine-Levin syndrome is (type 1) viral infections may encountered in adolescents and is trigger a sleepiness Narcolepsy without about 4 times more common in adoles- episode, but not on a cataplexy (type 2) cent males than females. The salient consistent basis. Secondary narcolepsy features of Kleine-Levin syndrome in- (eg, posttraumatic or clude periods of hypersomnia, inertia, postencephalitic) and feelings of depersonalization. Hy- b Psychiatric perphagia and hypersexual behavior Depression have been overemphasized and occur b Respiratory only in about 50% of patients. Periods of Obstructive hypoventilation extreme sleepiness occur, lasting 14 to Obstructive sleep apnea 18 hours per day for 1 to 2 weeks and, in about one-half of cases, may be associated with hyperphagia, anorexia, or electronic devices or cell phones; hypersexual behavior. Feelings of de- caffeine, tobacco, or illicit substance personalization, amnesia, and cognitive use at night; taking a warm shower or difficulties may also occur.11 In be- exercising close to bedtime; and eat- tween these episodes, the patients are ing or drinking in the middle of the completely normal. Several of these night. The sleep history should deter- episodes may occur per year. Inter- mine details regarding the sleep pe- current viral infections may trigger riod, including what time the patient a sleepiness episode, but not on goes to bed and when sleep onset a consistent basis. No genetic predis- occurs for both school nights and posing factors exist. Prior neuro- nonYschool nights. The physician logic and psychiatric history is also

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KEY POINT h About one-third of unremarkable. School attendance and sleep with heightened arousals. Based patients with narcolepsy the overall quality of life may be upon the presence or absence of experience the onset considerably impacted. No specific ab- cataplexy, the International Classifi- of symptoms in the normalities are seen on neuroimaging cation of Sleep Disorders, Third Edi- first or second decade tests or routine testing of the CSF. tion (ICSD-3) categorizes the disorder of childhood. Nocturnal polysomnography obtained into type 1 and type 2, respectively.14 during the first 2 to 3 days of sleepi- Type 1 is more common in childhood ness may show increased arousals, as compared to type 2. Narcolepsy decreased sleep efficiency, and sup- type 1 may have an onset anywhere pression in the proportion of time between 3 and 17 years of age. spent in N3 sleep. These findings may Familial clustering of narcolepsy is resolve in the latter half of the sleepy recognized, as the risk of developing period. During relapses, the CSF narcolepsy is 1% to 2% for first-degree hypocretin/orexin levels may be re- relatives of patients with narcolepsy duced in comparison to periods of (20-fold to 40-fold higher risk than remission, but the magnitude of de- in the general population).15 The creased CSF hypocretin is mild when haplotype human leukocyte antigen compared to patients with narcolepsy- DQB1*0602 is present in more than cataplexy.12 Empiric evidence sug- 95% of narcolepsy type 1 cases, as gests that lamotrigine and lithium are compared to a 25% to 30% prevalence modestly effective in preventing re- in the general population, and may lapses or decreasing the duration of predispose patients to narcolepsy with sleepy periods in patients with Kleine- cataplexy following likely triggers such Levin syndrome. In a recent open- as infections (commonly mycoplasma, label, controlled study, the risk-benefit Epstein-Barr virus, influenza, or strep- ratio of lithium was superior to no tococcus) or immunizations. Through therapy, presumably on account of mechanisms that are not yet fully anti-inflammatory or neuroprotective defined, there is likely to be activation effects.13 In general, Kleine-Levin syn- of an immune-mediated disturbance drome episodes become gradually that leads to near-complete loss of less frequent over time and gradually dorsolateral hypothalamic hypocretin- spontaneously resolve. secreting neurons.16 Hypocretinergic neurons project widely to the ventral Narcolepsy forebrain to enhance alertness and Narcolepsy is a prototypic disorder of also to areas of the brainstem to excessive sleepiness that occurs in modulate monoamine release and both adults and children, with about motor control. The loss of hypocretin one-third of patients having onset of leads to hypersomnia, cataplexy, and symptoms during the first or second unstable nocturnal sleep (with or decade. Narcolepsy is characterized by without periodic limb movements an overwhelming sleepiness, variable [PLMs] of sleep). Patients with narco- presence of sudden muscle weakness lepsy type 2 lack cataplexy and may provoked by emotional stimuli, fright, manifest hypersomnia, sleep paralysis, or the anticipation of a reward (cata- and hypnagogic hallucinations. Some plexy), vivid dreams at sleep onset individuals with narcolepsy type 2 may (hypnagogic hallucinations), transient develop cataplexy several years later, inability to move as the patient drifts thus evolving into narcolepsy type 1, off to sleep or wakes from sleep (sleep while others may have narcolepsy paralysis), and instability of nocturnal type 2 throughout their lives.

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Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINTS The most disabling clinical manifes- (MSLT). On the MSLT, the clinician is h Children with tation of childhood narcolepsy is pro- likely to find a decreased sleep latency narcolepsy may show found daytime sleepiness. Despite of fewer than 8 minutes and two or subtle cataplexy with 19 having slept through the night, the more sleep-onset REM periods. If transient jaw weakness patient may fall asleep involuntarily on the nocturnal polysomnogram has a or head rolling, and multiple occasions during the day sleep-onset REM period, the clinician laughter may not be a (while sitting at a desk, during con- needs to see only one additional consistent trigger versations, and even while eating). An sleep-onset REM period on the MSLT in children. increase in the total sleep time over to establish the diagnosis. Reference h Precocious puberty and the 24-hour period occurs around the values for the MSLT in children are obesity are other time of symptom onset and gradually slightly higher than those of adults. A common features reduces over months.17 The Epworth urine drug screen should be obtained accompanying the Sleepiness Scale for Children and routinely when the mean sleep latency onset of narcolepsy Adolescents or the Pediatric Daytime is fewer than 8 minutes. Caveats about type 1. Sleepiness Scale can be used to assess sleep laboratory evaluations are that the degree of sleepiness. Sleepiness testing is valid only in children older may be associated with mood swings, than 5 years of age, and that patients inattentiveness, and problems with must be drug free in the preceding memory and learning. Anxiety and 2 to 3 weeks prior to testing to avoid feelings of sadness may impair social confounding the results or masking interactions. Children younger than diagnostic sleep-onset REM periods ages 8 to 10 years may show subtle by stimulants or antidepressants that cataplexy in the form of transient jaw suppress and delay entry into REM weakness or head rolling; laughter sleep. CSF may show absent to very may not be a consistent trigger for low levels of hypocretin-1 (less than cataplexy in preschool-age children. 110 pg/dL) in patients with narcolepsy- Patients do not consistently report cataplexy.20 Hypocretin analysis has cataplexy; hence, the clinician may limited clinical availability in the need to probe with leading questions United States, but is helpful in en- concerning weakness provoked by abling diagnosis of narcolepsy type 1 emotions, characteristically by laugh- when polysomnography and MSLT are ter. When severe, cataplexy can lead not applicable (eg, in patients younger to falls or the legs feeling weak or than 5 years of age) or when the patient rubbery; when subtle, however, it may is receiving a REM-suppressant agent manifest itself only with momentary such as a selective serotonin reuptake masseter muscle weakness with the inhibitor (SSRI) that cannot be safely jaw dropping open or a slight head stopped because of concerns about and neck roll.17 Precocious puberty exacerbating comorbid depression. and obesity are other common fea- The differential diagnosis of narco- turesattheonsetofnarcolepsytype1.18 lepsy includes abnormal sleep hygiene Sleep at night may be disrupted by with consequent insufficient sleep at PLMs or REM sleep behavior disorder. night, drug-seeking behavior, depres- Diagnosis. The diagnosis of narco- sion, and circadian rhythm sleep-wake lepsy is generally established using disorders such as delayed sleep-wake nocturnal polysomnography (sleep- phase disorder. If a clinical suspicion onset REM period, fragmented sleep, of narcolepsy exists and sleep stud- and REM sleep without atonia are ies are equivocal, a serial battery of common findings), followed the next polysomnography and MSLT several day by the multiple sleep latency test months apart may be needed because

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polysomnographic features of narco- of alcohol. Physical activity is a useful lepsy may evolve gradually over time. antidote to sleepiness; hence, the Secondary narcolepsy as a conse- patient should exercise regularly. High quence of anatomic or metabolic brain school graduates may require counsel- lesions is rare, but can develop in ing about the choice of a career and patients with primary brain tumors course load in college. Referral to such as craniopharyngioma, head in- patient and family support organiza- jury, encephalitis, myotonic dystrophy tions such as the Narcolepsy Network type 1, and Niemann-Pick disease (narcolepsynetwork.org) or Wake Up type C (a disorder of intracellular cho- Narcolepsy (wakeupnarcolepsy.org) lesterol transport). is also recommended. Management. The first step in Regarding pharmacotherapy of nar- management is counseling. The pa- colepsy (Table 11-3), the clinician should tient and family should be informed initially target the symptom that is most that narcolepsy is a life-long disorder. bothersome to the patient. If sleepiness The sleep-wake schedule should be is the major concern, prescribing a for- regular, and planned naps of 20 to mulation of methylphenidate or am- 30 minutes should be put in place at phetamine or a wakefulness-promoting school or upon return home from agent such as modafinil or armodafinil school. Whenever possible, driving is recommended. Conversely, if cata- should be avoided, as should the use plexy is more bothersome, sodium

TABLE 11-3 Childhood Narcolepsy Pharmacotherapy

Symptom Drug Potential Side Effects Daytime sleepiness Methylphenidate Loss of appetite, suppression of growth, exacerbation of anxiety, nervousness Dextroamphetamine, amphetamine- Loss of appetite, suppression of growth, dextroamphetamine mixture exacerbation of anxiety, nervousness Modafinil, armodafinil Headache, precipitation of Stevens-Johnson syndrome, decreases the potency of concurrently administered oral contraceptives Sodium oxybate Tremor, constipation, bed-wetting, exacerbation of sleep apnea, weight loss, exacerbation of depression Cataplexy Sodium oxybate Tremor, constipation, bed-wetting, exacerbation of sleep apnea, weight loss, exacerbation of depression Venlafaxine, protriptyline, Drowsiness, weight gain, tremor clomipramine Fluoxetine, sertraline Nervousness, insomnia, increased risk of suicidal thoughts Periodic limb movements Gabapentin, elemental iron, Drowsiness (with gabapentin and clonazepam clonazepam), constipation and abdominal discomfort (with iron)

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Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited. oxybate (+-hydroxybutyrate) is recom- such as venlafaxine are also effective mended, since this medication targets against cataplexy. SSRIs and SNRIs are both cataplexy and sleepiness.21 preferred when cataplexy occurs in A potential disadvantage of conjunction with dysphoria. Most med- +-hydroxybutyrate is the potential for ications have side effects, with the misuse and drug diversion related to most significant side effects listed in its central nervous system depressant Table 11-3. Treatment guidelines for qualities, similar to those of alcohol narcolepsy in children are based on and benzodiazepines. When it comes expert opinion and consensus, since a to illicit use, the acronym GHB is sound evidence basis is currently lack- used, whereas for appropriate medical ing. Presently, an ongoing multicenter, use in narcolepsy, the term sodium placebo-controlled trial is investigating oxybate is applied.22 The dispensing the efficacy of sodium oxybate in child- of sodium oxybate is tightly regulated, hood narcolepsy-cataplexy. and the drug is shipped to the patient only through a centralized pharmacy. OBSTRUCTIVE SLEEP APNEA Tricyclics, SSRIs, and serotonin norepi- Key features of OSA are shown nephrine reuptake inhibitors (SNRIs) in Table 11-4. OSA is characterized

TABLE 11-4 Key Features of Childhood Obstructive Sleep Apnea

Feature Details Prevalence Approximately 2%; increased in those with premature birth, African American ethnicity Etiology Adenotonsillar hypertrophy, craniofacial anomalies, neuromuscular disorders, obesity; increased predilection in patients with Down syndrome, Prader-Willi syndrome, achondroplasia, Crouzon syndrome, kyphoscoliosis, and cerebral palsy Clinical Snoring not consistently observed in infants and those with neuromuscular disorders; manifestations habitual snoring, mouth breathing, restless sleep, hyperhidrosis, enuresis, increased tendency for sleepwalking and teeth grinding, feeling unrefreshed upon awakening in the morning, headache, somnolence, hyperactivity and inattentiveness, mood swings, failure to thrive (in infants) Diagnosis Abnormal overnight oximetry (in severe cases); nocturnal polysomnography may show increased apnea-hypopnea index (reference value is less than 1 per hour in contrast to 5 per hour in adults), increased tendency for partial occlusions rather than full apneas; upper airway sleep endoscopy and cine-MRI in cases with craniofacial anomalies Management For mild childhood obstructive sleep apnea (OSA), consider intranasal corticosteroids plus leukotriene inhibitor. For moderate to severe childhood OSA, consider adenotonsillectomy; repeat polysomnography 2 to 3 months after adenotonsillectomy to evaluate for residual OSA. If OSA persists, consider continuous positive airway pressure or bilevel positive airway pressure devices; consider weight reduction measures when obese. For intractable OSA, consider tongue base reduction surgery, genioglossus advancement, hyoid myotomy or suspension, tracheostomy, or rapid maxillary distraction. For infants with laryngotracheomalacia, consider supraglottoplasty. For infants with hypotonia-related collapse of the upper airway, consider low flow oxygen via nasal cannula (0.25Y0.5 L/min).

MRI = magnetic resonance imaging.

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KEY POINTS h Adenotonsillar by partial or complete upper airway oc- sleep, and impacts daytime alertness hypertrophy is the most clusion, with associated impaired air and behavior. The nocturnal symp- common etiology for exchange despite the persistence of toms of childhood OSA include habit- childhood obstructive thoracic and abdominal respiratory ual snoring, restless sleep with snort sleep apnea, followed effort. Associated cortical arousals may arousals, bed-wetting, excessive sweat- by craniofacial occur with or without transient oxygen ing, mouth breathing, choking sounds, anomalies, neuromuscular desaturation. In some instances, hypo- and increased predisposition to para- disorders, and obesity. ventilation may also be a component somnias such as confusional arousals h Infants with obstructive because of shallow abdominal and and sleepwalking. Parents may report sleep apnea may not chest wall motion. Based on commu- habitual snoring that is interrupted by consistently manifest nity surveys, the prevalence of child- silent pauses, which then terminate snoring and often hood OSA is estimated at about 2%.23 with snorting sounds. A metabolic syn- present with stridor Primary snoring is the mildest form of drome may develop as a consequence and laryngomalacia. sleep-related upper airway obstruction, of recurrent oxygen desaturation and h Neurobehavioral occurring in about 8% of children, and sympathetic overactivation. This is gen- manifestations such as is characterized by snoring at least 3 erally characterized by insulin resis- inattentiveness and nights per week without associated tance, hyperglycemia, hypertension, mood swings can be apnea, increased arousals from sleep, dyslipidemia, abdominal obesity, and clues to childhood or gas exchange abnormalities.24,25 As proinflammatory and prothrombotic obstructive sleep apnea. shown in Table 11-4, pediatric OSA states. Neurobehavioral manifestations differs from OSA in adults in several such as inattentiveness and mood different ways. swings can be clues to childhood OSA. The most common etiologic factors The daytime symptoms of OSA include for OSA in children are adenotonsil- inattentiveness, impaired academic per- lar hypertrophy, craniofacial anomalies formance, hyperactivity, and sleepi- such as micrognathia or maxillary hy- ness.24,27 Some children with OSA may poplasia, Down syndrome (Case 11-1), display aeroprotective maneuvers such obesity, and neuromuscular disorders as keeping the neck arched backward such as myotonic dystrophy or con- or sleeping prone on their knees and genital nonprogressive myopathies.23 elbows. Patients with neuromuscular Infants with OSA may not consistently disorders or hypotonia from central manifest snoring, often present with nervous system dysfunction tend to stridor and laryngomalacia, and may show more severe oxygen desaturation have a higher incidence of congenital during periods of REM sleep in the anomalies of the upper airway, such as supine position. choanal atresia. A superimposed inflammatory component contributes to OSA Diagnosis as well; levels of hydrogen peroxide may When clinical symptoms and signs of be elevated in the exhaled breath of OSA are obvious, clinicians can use children with OSA, suggesting increased nocturnal pulse oximetry in the home oxidative stress.27 Furthermore, eleva- environment for making the diagno- tions have been found in the serum lev- sis. The normal number of oxygen de- els of proinflammatory cytokines, such saturation events is about one per hour as tumor necrosis factor-!, interleukin-6, of sleep. Greater than three drops in and interleukin-8.28,29 oxygen saturation below the 90% level Repetitive occlusion of the upper may suggest OSA. The limitation of airway during sleep with resultant overnight oximetry is that it has a false- oxygen desaturation provokes cortical negative rate of about 70%; thus, ab- arousals, suppression of REM and N3 sence of oxygen desaturation episodes

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Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited. Case 11-1 A 9-year-old girl with Down syndrome presented with symptoms of nightly snoring, restless sleep, increased night awakenings, and a relapse of bed-wetting. She had also become increasingly disruptive in the classroom. Her height and weight were at the 50th and 90th percentiles, respectively, and her body mass index was 25 kg/m2. Examination revealed 3+ enlargement of the tonsils, an enlarged tongue size, and a tendency toward mouth breathing and inattentiveness and impulsivity. A nocturnal polysomnogram showed decreases in sleep efficiency of 78% (reference value of greater than 90%) and in rapid eye movement (REM) sleep at 13% of total sleep time (reference value of approximately 20%). The apnea-hypopnea index was elevated at 5 per hour (reference value in children of 1 per hour or less). Respiratory events were predominantly REM sleep-related obstructive hypopneas and obstructive sleep apneas (OSAs). The oxygen saturation nadir was 78%. The end-tidal carbon dioxide levels were 45 mm to 58 mm, and the percent of time with end-tidal carbon dioxide levels of greater than 50 mm was 28% of the total sleep time (reference value of 25% or less). Given the significant enlargement of the tonsils, she was referred to pediatric otolaryngology for adenotonsillectomy. Three months after surgery, her parents felt that her sleep was much improved, but that she was still snoring intermittently and remained inattentive. A repeat polysomnogram showed residual OSA with an apnea-hypopnea index of 3 per hour; she was provided a positive airway pressure (PAP) breathing device, with improvement in snoring and daytime behavior. Comment. This case illustrates several issues. About 70% to 75% of children with Down syndrome develop OSA. Consequently, the American Academy of Pediatrics recommends sleep assessment for all children with Down syndrome.26 OSA in Down syndrome is multifactorial and is related to a combination of the characteristic midface hypoplasia, enlarged tongue size, collapse of the hypotonic upper airway during REM sleep, tonsillar/adenotonsillar hypertrophy, and sleep-related hypoventilation. End-title carbon dioxide monitoring is essential in pediatric polysomnography because oxygen desaturation is not consistently seen, and shallow breathing or hypoventilation is common. Reference values for pediatric OSA differ from those of adults (ie, the normal apnea-hypopnea index in children is 1 per hour or less, in contrast to less than 5 per hour in adults). While adenotonsillectomy reduced the severity of OSA in this patient, she ultimately required a continuous PAP (CPAP) device to alleviate residual sleep apnea. Successful use of PAP devices in children with neurologic impairments is feasible but challenging owing to decreased patient comprehension and anxiety. It requires a gradual process of desensitization for mask and CPAP equipment over several weeks, utilizing the assistance of trained nursing staff or respiratory therapists. does not exclude OSA. Regardless, the of clinical symptoms of OSA and poly- test is helpful in facilitating diagnosis, somnographic findings is low, especially at least in those with severe OSA. Noc- in infants. In this age group, clinical turnal polysomnography is indicated symptoms may not be consistently when the diagnosis is uncertain. How- present, and the clinician may need to ever, correlation between the presence have a low threshold for ordering

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KEY POINT h Adenotonsillectomy is polysomnography. Polysomnography is constitute high-risk groups and should often the first step in indicated when patients with neu- be monitored carefully in the postop- management for rodevelopmental disabilities such as erative period for respiratory compro- obstructive sleep Down syndrome, epilepsy, or cerebral mise because of upper airway edema. apnea in children palsy present with restless or un- A clinical and, if necessary, polysomno- and adolescents. refreshing sleep. Polysomnography is graphic reevaluation should occur 2 to also indicated when the patient should 3 months after adenotonsillectomy. be given a nonsurgical treatment, such Behavior, quality of life, and polysom- as a positive airway pressure (PAP) nogram findings show significant im- device.30 Polysomnography helps dis- provement when adenotonsillectomy tinguish OSA from obstructive hypo- is provided early following initial pre- ventilation (the latter shows an end-tidal sentation, as compared to watchful carbon dioxide level of greater than waiting.32 Supraglottoplasty is indi- 50 mm for 25% of the recording time cated in infants with stridor and poor or more) and in identifying central weight gain during infancy. In children sleep apnea. The severity of the sleep- weighing more than 14 kg (30.8 lb), if disordered breathing can also be quan- residual OSA occurs, a PAP breathing tified using the apnea-hypopnea index device should be considered. PAP de- (number of apneas or hypopneas per vices are approved for use by the US hour of sleep). The pediatric otolaryn- Food and Drug Administration (FDA) gologist can conduct drug-induced in children weighing more than 14 kg endoscopy of the upper airway to (30.8 lb). A variety of masks and assess the sites of upper airway occlu- pressure delivery devices are now sion in sleep. available. The sleep-related obstructive hypoventilation of neuromuscular Management disorders may require bilevel PAP Mild OSA (an apnea-hypopnea index of to provide noninvasive ventilation.33 less than 3 per hour) is treated with Weight-reduction measures are indi- topical nasal corticosteroids at bed- cated in patients who are obese. time. In a randomized double-blind Orthodontic consultation and oral ap- crossover trial of intranasal budesonide pliances to pull the jaw and tongue (32 mcg in each nostril at bedtime) for forward in sleep are indicated in those the treatment of mild OSA, signifi- with retrognathia and tongue prolapse. cant improvement was shown in poly- Rapid maxillary distraction is a non- somnographic measures and adenoid surgical technique used in children size after 6 weeks in 48 children who with OSA who have a high arched received the topical steroid in compari- palate and consequent narrowing of son to 32 subjects on the placebo arm.31 the nasal passages. This procedure For moderate (an apnea-hypopnea opens up the suture between the two index of 3 to 9 per hour) or severe edges of the hard palate, promotes OSA (an apnea-hypopnea index of local bone development, and flattens more than 10 per hour), the first step the shape of the palate, thus indirectly in management is usually adenoton- increasing the diameter of the nasal sillectomy, to which most patients passages.34,35 respond favorably. Children younger than 3 years of age, children who have RESTLESS LEGS SYNDROME craniofacial anomalies, or those with Based on a survey of 10,523 families severe OSA (eg, an apnea-hypopnea from western Europe and the United index of greater than 10 per hour) States, the prevalence of RLS (also

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Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINTS referred to as Willis-Ekbom disease) in repetitive leg kicking and rubbing one h 36 39 Child-appropriate childhood is estimated at about 2%. legagainsttheother. Nocturnal language should be Between 25% and 40% of adult sub- polysomnography may be required in used when inquiring jects with RLS report onset of symp- nonverbal children for the documen- about symptoms of toms in childhood or adolescence. tation of PLMs, a finding that is restless legs syndrome. Although, among adults, the disorder present in approximately 80% of chil- h An overlap between is more common in women, the child- dren and adults with RLS. PLMs con- attention deficit hood form of RLS is equally common in stitute an important endophenotype hyperactivity disorder 40 boys and girls and occurs worldwide. for RLS. They are defined as a series and restless legs of four or more electromyographically syndrome exists. Clinical Features identified limb movements that last The current diagnostic criteria for RLS 0.5 to 5 seconds and occur at intervals are summarized in Table 11-5.37 RLS of 5 to 90 seconds, typically in non- is a sensorimotor disorder character- REM sleep. The physiologic PLM index ized by a discomfort in the extremities (movements per hour of sleep) is less that appears in the afternoon or late than 5 per hour. The partial arousals evening. RLS is worsened by keeping triggered by PLMs may activate non- the limbs still and relieved momentar- REM parasomnias such as confusional ily by movement. Children commonly arousals or sleepwalking. Frequent describe this uncomfortable sensation arousals from the accompanying sen- as a feeling of ‘‘bugs crawling,’’ sory discomfort or motor disturbance ‘‘owies,’’ ‘‘ouchies,’’ or ‘‘tickles’’ in may lead to daytime fatigue and the legs (Case 11-2). inattentiveness. An overlap occurs be- When inquiring about RLS in a tween attention deficit hyperactivity child, it is important to use child- disorder and RLS.25 appropriate terms. Children may de- The term growing pains refers to a scribe a ‘‘need to move’’ or ‘‘need to set of etiologically heterogeneous kick the legs.’’ Encouraging children symptoms of discomfort in the lower to depict their leg discomfort in extremities in children that may in- drawings also enables diagnosis.38 In clude musculoskeletal, arthritic, and preschool-age children, home video RLS symptoms. A subset of children observations may reveal a pattern of with growing pains may indeed have

TABLE 11-5 Considerations in the Diagnosis of Childhood-Onset Restless Legs Syndromea

b Patient has an urge to move the limbs that may be accompanied by an uncomfortable or unpleasant sensation in the legsb b This urge is made worse during periods of rest or inactivity b The urge to move the limbs and the uncomfortable or unpleasant sensation accompanying it are relieved partially or totally by movementc b The urge to move the limbs and the accompanying uncomfortable sensation are worse in the eveningsd a Data from Picchietti D, et al. Sleep Med.37 sleep-journal.com/article/S1389-9457(13)01070-8/ fulltext. b For children, the description of discomfort must be in the child’s own words (eg, ‘‘owies’’). c Mimics of restless legs syndrome that should be considered include myalgia, leg edema, arthritis, and leg cramps. d When symptoms are severe, symptoms may not show worsening at night.

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KEY POINT h Children with restless Case 11-2 legs syndrome generally A 9-year-old boy presented with difficulty falling and staying asleep, a have a strong family problem he had experienced for 4 years. At his bedtime of 8:00 PM or 8:30 PM, history for restless the child would be sleepy, but was unable to fall asleep for up to an hour. legs syndrome. He indicated a discomfort in his legs around bedtime as well as an urge to stretch and move his legs; keeping his legs still was uncomfortable. The patient intermittently experienced periods of sleepwalking, which occurred 2 to 3 hours after initial sleep onset. He also had attention deficit hyperactivity disorder. His mother had experienced similar symptoms in her childhood. His general physical and neurologic examinations were normal. A nocturnal polysomnogram showed total recording time of 436 minutes, total sleep time of 401 minutes, the periodic limb movement index was elevated at 49 (reference value of less than 5 per hour), and the apnea-hypopnea index was normal at 1 per hour, as was oxygen saturation and end-tidal carbon dioxide. The relative percentages of various sleep stages were normal. The hemoglobin was 11.8 g/dL, hematocrit was 34%, mean corpuscular volume was 77 2m3, and serum ferritin was 18 ng/mL. The boy had iron deficiency that was treated with ferrous sulfate tablets 325 mg/d. Gabapentin 100 mg at bedtime was added to provide symptomatic relief from the sensory discomfort of restless legs syndrome (RLS). Concurrent with a rise in the serum ferritin level to 39 ng/mL, the sleep quality improved over the next 2 to 3 months. Comment. Childhood-onset RLS may manifest as sleep initiation difficulty. Children of this age have limited ability to articulate their RLS symptoms. Polysomnography may be needed for documentation of elevated PLMs in sleep. Also, the use of child-appropriate terms in eliciting RLS history is recommended. For instance, asking about ‘‘owies’’ or ‘‘ouchies’’ in the legs will better elicit the sensory disturbance of RLS in children. A history of RLS is present in close to 75% of family members; hence, it is important to inquire about this. Systemic iron deficiency is the most common etiology for childhood RLS, so iron replacement therapy may need to be considered when children have iron insufficiency. The symptomatic improvement with oral iron may take several months. The target value of serum ferritin is about 50 ng/mL to 60 ng/mL. Gabapentin is a useful ‘‘bridge’’ during this period for providing symptomatic relief from the sensory discomfort. Finally, one should recognize the occurrence of attention deficit hyperactivity disorder in 30% to 40% of children with RLS.

RLS based on detailed clinical and Pathophysiology polysomnogram assessment for in- Genetic susceptibility, autosomal dom- creased PLMs.41 Polysomnography is inant mode of transmission, central needed as an aid for diagnosis in nervous system iron deficiency, and nonverbal children as they may not dysregulation of dopaminergic neuro- be able to clearly articulate the nature transmission all seem to play a role in of their symptoms. One historical clue causation of RLS. Children with RLS to clinically distinguish possible causes generally have a strong family history of growing pains is that rest and of the disorder in close to 75% of first- immobility will worsen RLS but relieve degree relatives.42 An element of antic- musculoskeletal causes. ipation may exist, consistent with the

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Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINT dominant mode of inheritance. In during a systemic infection, as the h Systemic iron deficiency contrast, the inheritance pattern in level may be falsely elevated. Medica- is a common predisposing 43 adults with RLS is likely polygenic. A tion history should also be sought, factor for restless legs study of linkage and genotype analysis especially for those that tend to exac- syndrome and periodic done exclusively in 23 German chil- erbate RLS such as risperidone, SSRIs, limb movements dren with RLS using 38 microsatellite diphenhydramine, and antiemetics in children. markers found an association of RLS such as metoclopramide. When pos- with susceptibility loci on MEIS1, SKOR1, sible, medications that may worsen and MAP2K5 genes, but not BTBD9.44 RLS should be either discontinued or The results of this study are difficult to changed to a drug less likely to aggra- compare with those of genome-wide vate symptoms. association studies in adults because of Systematic studies on the treatment the small number of subjects and of RLS in children are lacking. Evi- limited number of markers studied. dence about the efficacy of certain Systemic iron deficiency is a com- pharmacologic agents is based on mon predisposing factor for RLS and anecdotal observations. The first step PLMs in children. A probable associa- in treating childhood RLS is generally tion exists between reduction in the the correction of systemic iron defi- serum ferritin and frequency of PLMs ciency.46 Oral iron tablets or solutions per hour of sleep; patients with serum of ferrous sulfate or ferrous gluconate ferritin levels of less than 50 ng/mL are commonly used. The recom- showed a significantly higher PLM in- mended dose of the oral iron supple- dex as compared to those with levels ment is 3 mg/kg/d to 6 mg/kg/d. Side greater than 50 ng/mL.44,45 The PLM effects of oral iron include constipa- index decreased following oral iron tion, dark stools, and abdominal dis- replacement therapy. Iron is a cofactor comfort. Correction of iron deficiency for tyrosine hydroxylase, a rate-limiting may take weeks or months; hence, it step in the conversion of tyrosine to is important to counsel family mem- dopamine. Further support for the bers to be patient for improvement role of dopaminergic neurotransmis- of levels, which should be reassessed sion in the pathogenesis of RLS is that to ensure satisfactory recovery. In dopamine receptor agonists such as case of intolerance to oral iron, IV ropinirole or pramipexole alleviate iron sucrose can be administered in symptoms of RLS in adults. Secondary a bolus of 3 mg/kg to 6 mg/kg, with RLS from conditions such as periph- the dose not exceeding 120 mg to eral neuropathy, diabetes mellitus, 150 mg,47 which leads to a prompt chronic renal disease, and spinal cord rise in the serum ferritin level. In the lesionsislesscommoninchildren interim, symptomatic relief from the than in adults. discomfort of RLS can be provided by a low dose of an agent such as Management gabapentin(50mgto100mgat Assessment of serum ferritin is indi- bedtime). Light exercise in the eve- cated in initial assessment of chil- ning is helpful in some subjects with dren with RLS. Levels of ferritin below RLS, but firm evidence from clinical 30 ng/mL to 35 ng/mL may be associ- studies is lacking. Little available evi- ated with RLS. Serum ferritin is an dence exists for dopaminergic agents acute phase reactant, so caution must like ropinirole or pramipexole in be exercised in interpreting the result older teens, and their use is on an if the blood sample has been drawn empiric basis.

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KEY POINTS PARASOMNIAS h NonYrapid eye parents. On the following morning, movement arousal Parasomnias are episodic phenomena however, the child may have no parasomnias, such as that interrupt sleep. Aside from affect- recollection of the event at all. confusional arousals ing the child’s health, the events can Sleep terrors (night terrors) also and sleepwalking, often also disrupt the sleep of other family occur within 2 to 3 hours of sleep onset, occur during the first members. They may develop at the out of N3 sleep. Abrupt crying, scream- third of the night. transition from wakefulness to sleep, ing, sweating, piloerection, and agita- h Obstructive sleep during REM sleep, or during non-REM tion can occur. The patient becomes apnea, restless legs sleep. Parasomnias are most common extremely agitated for several minutes, syndrome, and anxiety in preschool-age children and gradu- once again with amnesia for the event are common precipitating ally decrease in incidence over the in the morning. factors for nonYrapid eye first decade. Sleepwalking is another non-REM movement sleep In a large prospective study, ap- sleep parasomnia; the patient may parasomnias. proximately 1000 children between simply sit up in bed or climb out of the ages of 2.5 and 6 years were bed and wander about the room or followed longitudinally.48 The overall house and carry out nonpurposeful prevalence rate was 39.8% for sleep activities with no recollection of the terrors, 25% for sleep enuresis, and events the following morning. 14.5% for sleepwalking. The occur- These three non-REM sleep para- rence of parasomnias in preschool- somnias show a genetic predisposition. age children was ubiquitous; 88% of OSA, RLS, gastroesophageal reflux, and the cohort manifested at least one anxiety may also act as precipitating parasomnia during the study period. factors by activating partial arousals Non-REM sleep parasomnias in- from sleep. clude confusional arousals, sleep ter- Non-REM sleep parasomnias most rors, and sleepwalking.49 They are also frequently arise during N3 sleep, but termed disorders of arousal, as they can sometimes be mistaken for noc- result from incomplete arousal from turnal frontal lobe seizures, which are non-REM sleep. Typically, these events instead most frequent during N1 or occur at the transition from deep non- N2 sleep. Seizures are typically much REM (sleep stage N3) sleep into the briefer in duration (seconds) and lighter stages of non-REM sleep (sleep occur randomly through the night stages N2 or N1) or wakefulness. Most duringN1orN2sleep.Nocturnal are likely to occur during the first polysomnography with a 16-channel third of night, as N3 sleep is most EEG montage may sometimes be prevalent at this time. required to confirm the diagnosis of Confusional arousals are more likely non-REM sleep parasomnias and ex- to occur in children between 2 and clude nocturnal epilepsy. 5 years of age. The child will abruptly The management of non-REM sleep awaken within 2 to 3 hours of sleep parasomnias includes treating any un- onset, sit up in bed, and moan or cry derlying triggering factors for additional out while appearing confused and arousal, such as OSA or RLS. Trouble- only partially responsive to verbal some, recurrent non-REM sleep para- commands. Autonomic dysfunction in somnias may require prophylaxis with the form of sweating, flushed face, or clonazepam for 4 to 6 months as it piloerection is minimal. The duration seems to decrease the tendency for of the events is 5 to 20 minutes, dur- partial arousals from sleep. Environmen- ing which the child remains inconsol- tal safety measures such as dead bolts able, much to the distress of the and motion sensors may be necessary

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Copyright © American Academy of Neurology. Unauthorized reproduction of this article is prohibited. KEY POINT in severe cases of sleepwalking to motor dream enactment accompanied h Rapid eye movement prevent injury. by REM sleep without atonia seen on sleep behavior disorder polysomnography. RBD is infrequent is infrequent during Nightmare Disorder during childhood, but may be seen as childhood, but may The ICSD-3 defines nightmares as an ancillary manifestation accompany- be seen as an ‘‘recurrent episodes of awakening ing narcolepsy or in association with ancillary manifestation from sleep with recall of intensely various neurodevelopmental disor- accompanying disturbing dream mentation, usually ders, brainstem lesions, or following narcolepsy or in involving fear or anxiety, but also administration of SSRIs in younger association with various anger, sadness, disgust, and other individuals, including children and ad- neurodevelopmental dysphoric emotions.’’49 Generally, full olescents.52,53 As in adults, the patient disorders, brainstem lesions, or following alertness occurs immediately upon will show motor dream enactment in administration of awakening after a nightmare with sleep and may yell out, kick, or flail selective serotonin intact recall of the dream experience. the extremities. A cosleeping adult or reuptake inhibitors in Additionally, the patient may have a sibling may be the target of the younger individuals, delayedreturntosleepafterthe aggressive motor behavior. Unlike in including children episode. The description of dreams adults, however, no recognized asso- and adolescents. in preschool-age children may be ciation exists with degenerative disor- simple and, in older children, may be ders such as synucleinopathies. The more elaborate. Posttraumatic stress nocturnal polysomnogram shows pre- disorder is associated with dream served muscle tone in REM sleep at content that may be distressing, with baseline, with episodic tendencies for themes of inflicted violence, death, or motor dream enactment. Melatonin in separation from close family mem- a dose of 1 mg to 3 mg at bedtime, bers.50 As muscle tone and mobility clonazepam 0.25 mg to 0.5 mg at are actively inhibited during REM sleep, bedtime, or discontinuation of predis- bodily movement is rare. Physical, emo- posing medications such as antidepres- tional, or sexual abuse may underlie sants are common management ap- recurrent nightmares in children. Sepa- proaches. For more information, refer ration anxiety or generalized anxiety to the article ‘‘Rapid Eye Movement disorder are other predisposing factors. Sleep Behavior Disorder and Other Recurrent nightmares require psycho- Rapid Eye Movement Sleep Para- logical evaluation to assess for anxiety, somnias’’ by Birgit HPgl, MD, and Alex stress, and other potential underlying Iranzo, MD,54 in this issue of Continuum. factors. Actigraphy and sleep logs may reveal prolonged initial sleep latency, CONCLUSION increased nocturnal activity, and sleep While pediatric sleep disorders share fragmentation.51 Cognitive-behavioral some common features with those of therapy is indicated in cases of intense, adults, the constantly changing age- disturbing nightmares. Reassurance and related normal values of sleep archi- rescripting the content of dreams to a tecture and sleep-related breathing more pleasant ending (so-called dream physiology, as well as continuous ongo- image rehearsal therapy) may also be ing brain development, make the field helpful. challenging. Concepts of pediatric sleep medicine can be easily integrated into Rapid Eye Movement Sleep the practice of child neurology. Patients Behavior Disorder with epilepsy, headache, neurodevel- REM sleep behavior disorder (RBD) is opmental disabilities, and learning characterized by aggressive or violent disabilities are especially likely to

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