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Patients With Disordered Sleep
Overview
Scholars have long sought the cause and nature of sleep and sleep disorders, yet theories have far exceeded clear facts. Plato, for example, believed that sleep was caused by vapors arising from the stomach and condensing in the head, and Hippocrates believed that sleep was the result of blood and its warmth retreating into the body. Both 16th- and 17th-century scholars debated whether sleep was induced by oxygen deprivation, accumulated toxins, or the daily thickening of blood that impaired spirits from entering the nerves. Despite these age-old theories, only in recent years have the mysteries of sleep been slowly unraveled. Indeed, we now know that sleep is an active biochemical process complete with various physiologic markers, stages, and patterns that, like vital signs, provide a basic indication of overall well-being. This chapter examines the biological and psychiatric aspects of normal and disordered sleep, followed by a brief discussion of the diagnosis and treatment of common sleep disorders.
Sleep Stages and Normal Sleep
Aserinsky and Kleitman (1953) were the first to investigate rapid eye movements during sleep. Kleitman postulated that depth of sleep could be assessed through eye motility, and he and Aserinsky began testing this hypothesis through direct observation of eye movements of infants during sleep. They noted slow rolling eye movements during the early stages of sleep that disappeared as sleep progressed, and they saw periods of rapid eye movements associated with irregular breathing and increased heart rate. They coined the terms non-rapid eye movement (NREM) to indicate the slow rolling rhythmic eye movements and rapid eye movement (REM) to indicate the fast erratic eye movements. In 1957, Kleitman and Dement discovered that REM and NREM sleep occurred cyclically throughout the night and named this overall NREM–REM pattern sleep architecture .
Polysomnography
Polysomnography is the “gold standard” method for evaluating sleep physiology and many clinical sleep disorders. It involves simultaneously recording multiple physiologic variables in a standardized fashion known as the polysomnogram (PSG). The parameters recorded by the PSG include, but are not limited to, the following:
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Electroencephalogram (EEG) : A recording of the electrical activity of cortical neurons via scalp electrodes that are placed in standardized positions, usually bilateral frontal, central, and occipital positions.
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Electro-oculogram (EOG) : A recording of eye movements bilaterally.
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Electrocardiogram (ECG) : A recording of heart rate and rhythm.
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Electromyogram (EMG) : A recording of the activity of the bilateral tibialis anterior muscles, and the submental (chin) muscles.
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Respiration : Recordings of nasal and oral airflow by means of pressure and thermal sensors, and recordings of thoracic and abdominal movements by means of respiratory inductance plethysmography.
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Pulse oximetry : A recording of blood oxygen hemoglobin saturation.
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Snore monitor : A detection and recording of snoring by means of a vibration sensor placed on the neck.
Through analysis of EEG, EMG, and EOG signals, the different sleep–wake stages are scored, typically by manual visual inspection by skilled technologists. From the epoch-by-epoch scoring, various metrics are presented in typical PSG reports, such as sleep onset, NREM sleep, REM sleep, and awakenings that occur throughout the night.
The waking state is defined by the PSG in the following manner: the EEG reveals low amplitude and mixed high frequencies with eyes open, and an occipital predominant 8 to 13 Hz wave pattern known as alpha waves when eyes are closed; the EMG reveals muscle tone and activity; and the EOG demonstrates variable eye movements, including blinking. Sleep onset is defined as the time elapsed from lights-out to the first epoch of NREM stage 1 sleep (N1). The transition to N1 involves replacement of alpha waves with mixed theta frequency waves, slow rolling eye movements, and the EMG may register a modest decrease in muscle activity. Some patients at the transition to sleep may engage in automatic behavior , a phenomenon in which very complex cognitive and behavioral tasks are performed outside of awareness.
Sleep is normally entered through NREM sleep. NREM sleep is divided into three stages identified by specific EEG criteria; REM is identified by a combination of findings on the EEG, EOG, and EMG.
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Stage N1 : Alpha waves, present during the waking state, account for less than 50% of an epoch (a 30-second interval on the PSG). The EEG frequencies are mixed but lower than those seen during wakefulness, usually with emergence of theta waves (4 to 7 Hz).
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Stage N2 : Theta activity continues in this stage, while two hallmark waveforms emerge: sleep spindles (rhythmic 12 to 14 Hz waves that last 0.5 seconds or more) and K-complexes (high-amplitude negative waves that are followed by a positive deflection, lasting 0.5 seconds or more).
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Stage N3 : Delta waves (high-amplitude, slow-frequency 0.5 to 2.0 Hz waves) occur in at least 20% of an epoch. This stage is commonly called delta sleep or slow-wave sleep.
REM sleep, also known as paradoxical sleep owing to its similarity to wakefulness, is defined by three principal features. First, the EEG demonstrates low-amplitude high-frequency waves that may resemble those of wake or NREM stage 1. Second, the chin EMG reveals an absence of, or a marked decrease in, muscle activity. Finally, conjugate rapid eye movements become evident, often in bursts (phasic REM) separated by quiescent periods (tonic REM), on the EOG.
Perception of sleep state, as well as sleep quality, is not as straightforward as it might seem. For example, the subjective experience of sleep-onset latency, of awakenings during the night, or total sleep time, often differ from objective measures. Healthy individuals, for example, who may feel that their sleep is consolidated, actually have multiple brief awakenings throughout the night when measured by EEG. Thus, they may over-estimate their total sleep time by 20 minutes or more. In contrast, patients with insomnia often have the opposite trend: under-estimating their total sleep, and over-estimating the time spent awake. Another example of dissociation of physiology and symptoms may occur in patients with sleep apnea (discussed below), who may not have symptoms of sleepiness or disturbed sleep, even when their apnea is severe by objective measurements.
Case 1
Mr. A, a 52-year-old man with chronic depression, managed with a stable dose of an SSRI, noted gradually worsening fatigue over the past year. Upon questioning about associated changes in his mood, he reported that he was concerned about the fatigue and could not be certain whether it was from worsening mood, or if the mild worsening in mood was from the fatigue. He had gained 10 pounds. Although he denied snoring and his wife has not noticed any breathing problems, he had an elevated body mass index and hypertension. You correctly surmised that he was at elevated risk of obstructive sleep apnea (OSA) and you recommended a polysomnogram (PSG). The test indeed revealed moderate OSA, and Mr. A agreed to a trial of continuous positive airway pressure (CPAP), but he found that he could not tolerate the mask. After consultation with a sleep physician to discuss alternatives, Mr. A was referred to a dental specialist who fitted an oral appliance. He returned to report that his mood and fatigue were substantially improved.
Sleep Cycle and Architecture
NREM and REM sleep do not occur randomly throughout the night; instead, they alternate in a rhythmic fashion known as the NREM–REM cycle every approximately 90 to 120 minutes. N3 is most prominent in the first half of the night and diminishes thereafter. REM sleep shows the opposite pattern, with longer blocks as the night progresses. The time from sleep onset to the first REM is known as REM latency , which is usually 90 to 100 minutes. Sleep efficiency is the actual amount of sleep per total time in bed multiplied by 100, and is typically 85% or greater when measured by PSG in normal individuals. The average amount of sleep per night for adults is between 6 and 9 hours. The proportion of total sleep consisting of each sleep–wake stage in an average night are as follows: N1, 2% to 5%; N2, 45% to 55%; N3, 15% to 25%; and REM sleep, 20% to 25%.
Sleep Across the Life Span
Sleep quantity and sleep quality change across the life span. Infants spend about two-thirds of the day sleeping, whereas in adulthood, this amount decreases to less than one-third. Sleep architecture becomes altered as people age. These changes include increases in sleep latency, nocturnal awakenings, time spent in N1 sleep, and decreases in N3 sleep, REM sleep, and overall sleep efficiency.
Neuroanatomic Basis for Sleep
The actual neuroanatomic basis for the sleep–wake cycle remains uncertain, but current research reveals that specific regions of the brain are critical for wakefulness and for sleep. These neuronal systems are located in the brainstem, hypothalamus, and basal forebrain, and they project diffusely throughout the neocortex. The major wake-promoting centers include the tuberomammillary nucleus (TMN; histamine), the reticular activating system (serotonin), the locus ceruleus (norepinephrine), the basal forebrain (acetylcholine), and the hypothalamus (orexin). The major NREM sleep-promoting nucleus is known as the ventrolateral preoptic nucleus (VLPO; GABA). The pedunculopontine and laterodorsal tegmental (PPT/LDT) nuclei of the brainstem, both cholinergic with projections mainly to the thalamus, play an important role in REM sleep circuitry.
The timing of sleep and of wakefulness is largely determined by an internal biological cycle known as the circadian rhythm . This biological clock is an endogenous rhythm of bodily functions that is influenced by environmental cues, or zeitgebers , of which the main one is daylight. The average cycle is slightly longer than 24 hours for most people. The suprachiasmatic nuclei (SCN), in the anterior hypothalamus, is the brain region that controls human circadian rhythms. The SCN receives input from the eyes via the retino–hypothalamic tract, and it sends output to the hypothalamus and the pineal gland. Melatonin, a hormone secreted by the pineal gland during darkness (and production is suppressed by light), is associated with suppression of the SCN; it facilitates sleep in diurnal mammals.
Sleep disorders related to the circadian rhythm emerge when a person's circadian rhythm clashes with environmental and societal expectations.
A second kind of “clock” exists, independent of the circadian rhythm discussed above that is controlled by the SCN. This homeostatic sleep system tracks how much sleep has occurred recently, such that over time spent awake, homeostatic pressure accumulates to increase the probability of sleep. The biological basis for this system is thought to reside in adenosine levels, which build during wakefulness and wane during sleep. Caffeine is thought to improve wakefulness by blocking adenosine signaling.
Sleep Disorders
Although several classification systems for sleep disorders exist, the Diagnostic and Statistical Manual of Mental Disorders , 5th edition (DSM-5) and the International Classification of Sleep Disorders , 3rd edition (ICSD-3) are the most widely used.
Insomnia
Insomnia is a repeated difficulty with sleep initiation, duration, consolidation, or quality, despite adequate opportunity for sleep, which produces daytime impairment. Patients complain of deficient, inadequate, or unrefreshing sleep; malaise; and fatigue. Sufferers often experience hyperarousal and anxiety at bedtime and have decreased daytime function with mild to moderate impairment in concentration and psychomotor function.
Diagnosis
The diagnosis of insomnia is made exclusively based on the clinical history, which includes difficulty falling asleep or staying asleep, associated with non-refreshing sleep or some other daytime sequelae. The etiology of insomnia is often multi-factorial, but the final common pathway is postulated to be a state of increased arousal. There is evidence of increased arousal during sleep as well as during wakefulness in neuroimaging studies of patients with insomnia. A PSG is not typically recommended for evaluation of patients with chronic insomnia, unless another sleep disorder, such as periodic limb movements of sleep (PLMS) or OSA, is suspected.
Psychophysiologic insomnia is caused by somatized tension and by learned sleep-preventing associations. Sufferers react to stress with increased physiologic arousal, such as increased muscle tension and vasoconstriction. Learned associations consist mainly of an over-concern with an inability to sleep, which results in a vicious cycle of over-concern, increased arousal, insomnia, and reinforcement of concern. Environmental cues also become associated with an inability to sleep, and sufferers often report sleeping better in unfamiliar surroundings, including sometimes even in the sleep laboratory.
Paradoxical insomnia , also known as sleep-state misperception, involves a dissociation between often severe complaints of inadequate sleep and objective findings on the PSG showing fairly normal duration and content of sleep. Patients with sleep-state misperception may under-estimate their total sleep time or over-estimate their sleep latency, or both. Theories to explain this discrepancy include excessive mentation during sleep and obsessiveness about sleep.
Idiopathic insomnia is a chronic primary insomnia that develops in childhood and is most likely the result of an innate abnormality in the sleep–wake cycle. Prolonged sleep latency and poor sleep efficiency may be seen on PSG. The presence of psychiatric or medical conditions that better account for the symptoms is called insomnia due to a medical condition or mental disorder .
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