Sleep Medicine

Basics of Sleep and Chronobiology

Sleep, with its counterpart of wakefulness, is a highly complex and intricately regulated neurobiologic system that both influences and is influenced by all physiologic systems in the body, as well as by the environment and sociocultural practices. The concept of sleep regulation is based on what is usually referred to as the “2-process model” because it requires the simultaneous operation of 2 basic, highly coupled processes that govern sleep and wakefulness. The homeostatic process (“Process S”), regulates the length and depth of sleep and is thought to be related to the accumulation of adenosine and other sleep-promoting chemicals (“somnogens”), such as cytokines, during prolonged periods of wakefulness. This sleep pressure appears to build more quickly in infants and young children, thus limiting the duration that wakefulness can be sustained during the day and necessitating periods of daytime sleep (i.e., naps). The endogenous circadian rhythms (“Process C”) influence the internal organization of sleep and the timing and duration of daily sleep–wake cycles and govern predictable patterns of alertness throughout the 24 hr day.

The “master circadian clock” that controls sleep–wake patterns, of which melatonin secretion is the principal biomarker, is located in the suprachiasmatic nucleus in the ventral hypothalamus. In addition, “circadian clocks” are present in virtually every cell in the body, which in turn govern the timing of multiple other physiologic systems (e.g., cardiovascular reactivity, hormone levels, renal and pulmonary functions). Because the human circadian clock is slightly longer than 24 hr, intrinsic circadian rhythms must be synchronized or “entrained” to the 24 hr day cycle by environmental cues called zeitgebers. The dark–light cycle is the most powerful of the zeitgebers; light signals are transmitted to the suprachiasmatic nucleus via the circadian photoreceptor system within the retina (functionally and anatomically separate from the visual system), which switch the pineal gland's production of the hormone melatonin off (light) or on (dark). Circadian rhythms are also synchronized by other external time cues, such as timing of meals and alarm clocks.

Sleep propensity, the relative level of sleepiness or alertness experienced at any given time during a 24 hr period, is partially determined by the homeostatic sleep drive , which in turn depends on the duration and quality of previous sleep and the amount of time awake since the last sleep period. Interacting with this sleep homeostat is the 24 hr cyclic pattern or rhythm characterized by clock-dependent periods of maximum sleepiness ( circadian troughs ) and maximum alertness ( circadian nadirs ). There are two periods of maximum sleepiness, one in the late afternoon (approximately 3:00-5:00 pm ) and one toward the end of the night (around 3:00-5:00 am ), and two periods of maximum alertness, one in mid-morning and one in the evening just before the onset of natural sleep, the so-called forbidden zone or second-wind phenomenon, which allows for the maintenance of wakefulness in the face of accumulated sleep drive.

There are significant health, safety, and performance consequences of failure to meet basic sleep needs, termed insufficient/inadequate sleep or sleep loss . Sufficient sleep is a biologic imperative, necessary for optimal brain and body functioning. Slow-wave sleep (SWS) (i.e., N3, delta, or deep sleep) appears to be the most restorative form of sleep; it is entered relatively quickly after sleep onset, is preserved in the face of reduced total sleep time, and increases (rebounds) after a night of restricted sleep. These restorative properties of sleep may be linked to the “glymphatic system,” which increases clearance of metabolic waste products, including β-amyloid, produced by neural activity in the awake brain. Rapid eye movement (REM) sleep (stage R or “dream” sleep) appears to be involved in numerous important brain processes, including completion of vital cognitive functions (e.g., consolidation of memory), promoting the plasticity of the central nervous system (CNS), and protecting the brain from injury. Sufficient amounts of these sleep stages are necessary for optimal cognitive functioning and emotional and behavioral self-regulation.

Partial sleep loss (i.e., sleep restriction) on a chronic basis accumulates in a sleep debt and over several days produces deficits equivalent to those seen under conditions of 1 night of total sleep deprivation. If the sleep debt becomes large enough and is not voluntarily repaid by obtaining sufficient recovery sleep, the body may respond by overriding voluntary control of wakefulness. This results in periods of decreased alertness, dozing off, and unplanned napping, recognized as excessive daytime sleepiness. The sleep-restricted individual may also experience very brief (several seconds) repeated daytime microsleeps, of which the individual may be completely unaware, but which nonetheless may result in significant lapses in attention and vigilance. There is also a relationship between the amount of sleep restriction and performance on cognitive tasks, particularly those requiring sustained attention and higher-level cognitive skills ( executive functions ; see Chapter 48 ), with a decay in performance correlating with declines in sleep amounts.

It has also been increasingly recognized that what may be globally described as “deficient” sleep involves alterations in both amount and timing of sleep. Misalignment of intrinsic circadian rhythms with extrinsic societal demands, such a shift work and early school start times, is associated with deficits in cognitive function and self-regulation, increased emotional and behavioral problems and risk-taking behaviors, and negative impacts on health, such as increased risk of cardiovascular disease, obesity, and metabolic dysfunction.

Insufficient quantity of sleep, mistimed sleep, and poor-quality sleep in children and adolescents frequently result in excessive daytime sleepiness and decreased daytime alertness levels. Sleepiness in children may be recognizable as drowsiness, yawning, and other classic “sleepy behaviors,” but can also manifest as mood disturbance, including complaints of moodiness, irritability, emotional lability, depression, and anger; fatigue and daytime lethargy, including increased somatic complaints (headaches, muscle aches); cognitive impairment, including problems with memory, attention, concentration, decision-making, and problem solving; daytime behavior problems, including hyperactivity, impulsivity, and noncompliance; and academic problems, including chronic tardiness related to insufficient sleep and school failure resulting from chronic daytime sleepiness.

Developmental Changes in Sleep

Sleep disturbances, as well as many characteristics of sleep itself, have some distinctly different features in children from sleep and sleep disorders in adults. Changes in sleep architecture and the evolution of sleep patterns and behaviors reflect the physiologic/chronobiologic, developmental, and social/environmental changes that are occurring across childhood. These trends may be summarized as the gradual assumption of more adult sleep patterns as children mature:

• 1

  Sleep is the primary activity of the brain during early development; for example, by age 2 yr, the average child has spent 9500 hr (approximately 13 mo) asleep vs 8000 hr awake, and between 2 and 5 yr, the time asleep is equal to the time awake.

• 2

  There is a gradual decline in the average 24 hr sleep duration from infancy through adolescence, which involves a decrease in both diurnal and nocturnal sleep amounts. The decline in daytime sleep (scheduled napping) results in termination of naps typically by age 5 yr. There is also a gradual continued decrease in nocturnal sleep amounts into late adolescence; however, the typical adolescent still requires 8-10 hr of sleep per night.

• 3

  There is also a decline in the relative percentage of REM sleep from birth (50% of sleep) through early childhood into adulthood (25–30%), and a similar initial predominance of SWS that peaks in early childhood, drops off abruptly after puberty (40–60% decline), and then further decreases over the life span. This SWS preponderance in early life has clinical significance; for example, the high prevalence of partial arousal parasomnias (sleepwalking and sleep terrors) in preschool and early school-age children is related to the relative increased percentage of SWS in this age-group.

• 4

  The within-sleep ultradian cycle lengthens from about 50 min in the term infant to 90-110 min in the school-age child. This has clinical significance in that typically a brief arousal or awakening occurs during the night at the termination of each ultradian cycle. As the length of the cycles increase, there is a concomitant decrease in the number of these end-of-cycle arousals (night wakings).

• 5

  A gradual shift in the circadian sleep–wake rhythm to a delayed (later) sleep onset and offset time, linked to pubertal stage rather than chronological age, begins with pubertal onset in middle childhood and accelerates in early to mid-adolescence. This biologic phenomenon often coincides with environmental factors, which further delay bedtime and advance wake time and result in insufficient sleep duration, including exposure to electronic “screens” (television, computer) in the evening, social networking, academic and extracurricular demands, and early (before 8:30 am ) high school start times.

• 6

  Increasing irregularity of sleep–wake patterns is typically observed across childhood into adolescence; this is characterized by increasingly larger discrepancies between school night and non–school night bedtimes and wake times, and increased “weekend oversleep” in an attempt to compensate for chronic weekday sleep insufficiency. This phenomenon, often referred to as “social jet lag,” not only fails to adequately address performance deficits associated with insufficient sleep on school nights, but further exacerbates the normal adolescent phase delay and results in additional circadian disruption (analogous to that experienced by shift workers).

Table 31.1 lists normal developmental changes in children's sleep.

Common Sleep Disorders

Childhood sleep problems may be conceptualized as resulting from (1) inadequate duration of sleep for age and sleep needs (insufficient sleep quantity); (2) disruption and fragmentation of sleep (poor sleep quality) as a result of frequent, repetitive, and brief arousals during sleep; and (3) misalignment of sleep–wake timing with circadian rhythms or CNS-mediated hypersomnia (excessive daytime sleepiness and increased sleep needs). Insufficient sleep is usually the result of difficulty initiating ( delayed sleep onset ) or maintaining sleep ( prolonged night wakings ), but, especially in older children and adolescents, may also represent a conscious lifestyle decision to sacrifice sleep in favor of competing priorities, such as homework and social activities. The underlying causes of delayed sleep onset/prolonged night wakings or sleep fragmentation may in turn be related to primarily behavioral factors (e.g., bedtime resistance resulting in shortened sleep duration) or medical causes (e.g., obstructive sleep apnea causing frequent, brief arousals).

Certain pediatric populations are relatively more vulnerable to acute or chronic sleep problems. These include children with medical problems, such as chronic illnesses or pain conditions (e.g., cystic fibrosis, asthma, idiopathic juvenile arthritis) and acute illnesses (e.g., otitis media); children taking stimulants s (e.g., psychostimulants, caffeine), sleep-disrupting medications (e.g., corticosteroids), or daytime-sedating medications (some anticonvulsants, α-agonists); hospitalized children; and children with a variety of psychiatric disorders, including attention-deficit/hyperactivity disorder (ADHD), depression, bipolar disorder, and anxiety disorders. Children with neurodevelopmental disorders such as autism, intellectual disability, blindness, and some chromosomal syndromes (e.g., Smith-Magenis, fragile X) have especially high rates of sleep disturbances for a wide variety of reasons. They may have comorbid medical issues or may be taking sleep-disrupting medications, may be more prone to nocturnal seizures, may be less easily entrained by environmental cues and thus more vulnerable to circadian disruption, and are more likely to have psychiatric and behavioral comorbidities that further predispose them to disrupted sleep.

Insomnia of Childhood

Insomnia is defined as difficulty initiating and/or maintaining sleep that occurs despite age-appropriate time and opportunity for sleep and results in some degree of impairment in daytime functioning for the child and/or family (ranging from fatigue, irritability, lack of energy, and mild cognitive impairment to effects on mood, school performance, and quality of life). Insomnia may be of a short-term and transient nature (usually related to an acute event) or may be characterized as long-term and chronic. Insomnia is a set of symptoms with many possible etiologies (e.g., pain, medication, medical/psychiatric conditions, learned behaviors). As with many behavioral issues in children, insomnia is often primarily defined by parental concerns rather than by objective criteria, and therefore should be viewed in the context of family (maternal depression, stress), child (temperament, developmental level), and environmental (cultural practices, sleeping space) considerations.

While current terminology ( Diagnostic and Statistical Manual of Mental Disorders, 5th edition, 2015; International Classification of Sleep Disorders, 3rd edition, 2014) groups most types of insomnia in both children and adults under a single category of Chronic Insomnia Disorder, the descriptor of Behavioral Insomnia of Childhood and its subtypes (Sleep Onset Association and Limit Setting) remains a useful construct, particularly for young children (0-5 yr) in clinical practice. One of the most common presentations of insomnia found in infants and toddlers is the sleep-onset association type. In this situation the child learns to fall asleep only under certain conditions or associations, which typically require parental presence, such as being rocked or fed, and does not develop the ability to self-soothe. During the night, when the child experiences the type of brief arousal that normally occurs at the end of an ultradian sleep cycle or awakens for other reasons, the child is not able to get back to sleep without those same associations being present. The infant then “signals” the parent by crying (or coming into the parents' bedroom, if the child is ambulatory) until the necessary associations are provided. The presenting complaint is typically one of prolonged night waking requiring caregiver intervention and resulting in insufficient sleep (for both child and parent).

Management of night wakings should include establishment of a set sleep schedule and bedtime routine and implementation of a behavioral program. The treatment approach typically involves a program of rapid withdrawal (extinction) or more gradual withdrawal (graduated extinction) of parental assistance at sleep onset and during the night. Extinction (“cry it out”) involves putting the child to bed at a designated bedtime, “drowsy but awake,” to maximize sleep propensity and then systematically ignoring any protests by the child until a set time the next morning. Although it has considerable empirical support, extinction is often not an acceptable choice for families. Graduated extinction involves gradually weaning the child from dependence on parental presence; typically, the parent leaves the room at “lights out” and then returns or “checks” periodically at fixed or successively longer intervals during the sleep–wake transition to provide brief reassurance until the child falls asleep. The exact interval between checks is generally determined by the parents' tolerance for crying and the child's temperament. The goal is to allow the infant or child to develop skills in self-soothing during the night, as well as at bedtime. In older infants and young children, the introduction of more appropriate sleep associations that will be readily available to the child during the night (transitional objects, such as a blanket or toy), in addition to positive reinforcement (stickers for remaining in bed), is often beneficial. If the child has become habituated to awaken for nighttime feedings (learned hunger), these feedings should be slowly eliminated. Parents must be consistent in applying behavioral programs to avoid inadvertent, intermittent reinforcement of night wakings. They should also be forewarned that crying behavior often temporarily escalates at the beginning of treatment ( postextinction burst ).

Bedtime problems, including stalling and refusing to go to bed, are more common in preschool-age and older children. This type of insomnia is frequently related to inadequate limit setting and is often the result of parental difficulties in setting limits and managing behavior in general and the inability or unwillingness to set consistent bedtime rules and enforce a regular bedtime. The situation may be exacerbated by the child's oppositional behavior. In some cases the child's resistance at bedtime is the result of an underlying problem in falling asleep that is caused by other factors (medical conditions such as asthma or medication use; a sleep disorder such as restless legs syndrome; anxiety) or a mismatch between the child's intrinsic circadian rhythm (“night owl”) and parental expectations regarding an “appropriate” bedtime.

Successful treatment of limit-setting sleep problems generally involves a combination of parent education regarding appropriate limit setting, decreased parental attention for bedtime-delaying behavior, establishment of bedtime routines, and positive reinforcement (sticker charts) for appropriate behavior at bedtime. Other behavioral management strategies that have empirical support include bedtime fading , or temporarily setting the bedtime closer to the actual sleep-onset time and then gradually advancing the bedtime to an earlier target bedtime. Older children may benefit from being taught relaxation techniques to help themselves fall asleep more readily. Following the principles of healthy sleep practices for children is essential ( Table 31.2 ).

Table 31.2

Basic Principles of Healthy Sleep for Children

• 1

  Have a set bedtime and bedtime routine for your child.

• 2

  Bedtime and wake-up time should be about the same time on school nights and non–school nights. There should not be more than about 1 hr difference from one day to another.

• 3

  Make the hour before bed shared quiet time. Avoid high-energy activities, such as rough play, and stimulating activities, such as watching television or playing computer games, just before bed.

• 4

  Don ' t send your child to bed hungry. A light snack (e.g., milk and cookies) before bed is a good idea. Heavy meals within 1 hr or 2 of bedtime, however, may interfere with sleep.

• 5

  Avoid products containing caffeine for at least several hours before bedtime. These include caffeinated sodas, coffee, tea, and chocolate.

• 6

  Make sure your child spends time outside every day, whenever possible, and is involved in regular exercise.

• 7

  Keep your child 's bedroom quiet and dark. A low-level night light is acceptable for children who find completely dark rooms frightening.

• 8

  Keep your child 's bedroom at a comfortable temperature during the night (<24°C [75°F]).

• 9

  Don ' t use your child 's bedroom for time-out or punishment.

• 10

  Keep the television set out of your child 's bedroom. Children can easily develop the bad habit of “needing” the television to fall asleep. It is also much more difficult to control your child's viewing if the set is in the bedroom.

A 3rd type of childhood insomnia is related to a mismatch between parental expectations regarding time in bed and the child's intrinsic sleep needs. If, as illustrated in Fig. 31.1 , a child's typical sleep time is 10 hr but the “sleep window” is set for 12 hr (7 pm to 7 am ), the result is likely to be a prolonged sleep onset of 2 hr, an extended period of wakefulness during the night, or early morning waking (or a combination); these periods are usually characterized by “normal” wakefulness in the child that is not accompanied by excessive distress. This situation is important to recognize because the solution—reducing the time in bed to actual sleep time—is typically simple and effective.

Another form of insomnia that is more common in older children and adolescents is often referred to as psychophysiologic, primary, or learned insomnia. Primary insomnia occurs mainly in adolescents and is characterized by a combination of learned sleep-preventing associations and heightened physiologic arousal resulting in a complaint of sleeplessness and decreased daytime functioning. A hallmark of primary insomnia is excessive worry about sleep and an exaggerated concern of the potential daytime consequences. The physiologic arousal can be in the form of cognitive hypervigilance , such as “racing” thoughts; in many individuals with insomnia, an increased baseline level of arousal is further intensified by this secondary anxiety about sleeplessness. Treatment usually involves educating the adolescent about the principles of healthy sleep practices ( Table 31.3 ), institution of a consistent sleep–wake schedule, avoidance of daytime napping, instructions to use the bed for sleep only and to get out of bed if unable to fall asleep ( stimulus control ), restricting time in bed to the actual time asleep ( sleep restriction ), addressing maladaptive cognitions about sleep, and teaching relaxation techniques to reduce anxiety.

Table 31.3

Basic Principles of Healthy Sleep for Adolescents

• 1

  Wake up and go to bed at about the same time every night. Bedtime and wake-up time should not differ from school to non–school nights by more than approximately 1 hr.

• 2

  Avoid sleeping in on weekends to “catch up” on sleep. This makes it more likely that you will have problems falling asleep.

• 3

  If you take naps , they should be short (no more than 1 hr) and scheduled in the early to mid-afternoon . However, if you have a problem with falling asleep at night, napping during the day may make it worse and should be avoided.

• 4

  Spend time outside every day. Exposure to sunlight helps to keep your body's internal clock on track.

• 5

  Exercise regularly. Exercise may help you fall asleep and sleep more deeply.

• 6

  Use your bed for sleeping only. Don't study, read, listen to music, or watch television on your bed.

• 7

  Make the 30-60 minutes before bedtime a quiet or wind-down time . Relaxing, calm, enjoyable activities, such as reading a book or listening to calm music, help your body and mind slow down enough to let you get to sleep. Don't study, watch exciting/scary movies, exercise, or get involved in “energizing” activities just before bed.

• 8

  Eat regular meals, and don ' t go to bed hungry . A light snack before bed is a good idea; eating a full meal within 1 hr before bed is not.

• 9

  Avoid eating or drinking products containing caffeine from dinnertime to bedtime. These include caffeinated sodas, coffee, tea, and chocolate.

• 10

  Do not use alcohol. Alcohol disrupts sleep and may cause you to awaken throughout the night.

• 11

  Smoking (e.g., cigarettes) disturbs sleep. Although you should not smoke at all, if you do, do not smoke at least 2 hr before bed .

• 12

  Do not use sleeping pills, melatonin, or other nonprescription sleep aids to help you sleep unless specifically recommended by your doctor. These can be dangerous, and the sleep problems often return when you stop taking the medicine.

Behavioral treatments for insomnia, even in young children, appear to be highly effective and well tolerated. Several studies have failed to demonstrate long-term negative effects of behavioral strategies such as “sleep training” on parent–child relationships and attachment, psychosocial-emotional functioning, and chronic stress. In general, hypnotic medications or supplements such as melatonin are infrequently needed as an adjunct to behavioral therapy to treat insomnia in typically developing and healthy children.