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Childhood sleep disorders: diagnostic and therapeutic approaches.

Pediatric sleep physiology begins with development of the sleep/wake cycle, and the origins of active versus quiet sleep. The 24-hour circadian cycle becomes established at 3 to 6 months. Sleep disorders are rationally approached in pediatrics as age-related. Disorders during infancy commonly include mild, usually self-limited conditions such as sleep-onset association disorder, excessive nighttime feedings, and poor limit-setting. These require behavioral management to avoid long-term deleterious sleep habits. In contrast, other sleep disorders are more ominous, including sudden infant death syndrome (SIDS), central congenital hypoventilation syndrome, and sleep apnea. Childhood is generally the golden age of sleep, with brief latency, high efficiency, and easy awakening. Parasomnias, sometimes stage specific, are manifest here. Adolescents have sleep requirements similar to preteens, posing a challenge for them to adapt to school schedules and lifestyles. Narcolepsy, usually diagnosed in adolescence or early adulthood, is a lifelong sleep disorder that has led to the identification of the hypocretin/orexin neurotransmitter system. This will lead to enhanced understanding of what regulates stage rapid eye movement, and to novel therapeutic advances for hypersomnolence.

Adolescent↗

Sleep-related violence.

We hypothesized that sleep-related violent behavior associated with parasomnias occurs as the result of a diathesis and is precipitated by stressors and mediated by disturbed nonrapid eye movement (NREM) sleep physiology. Sixty-four consecutive adult patients (mean age 30 years) who were investigated for sleepwalking or sleep terrors were categorized according to clinical history into three groups: serious violence during sleep to other people or to property or self (n = 26); harmful, but not destructive behavior (n = 12); and nonviolent behavior (n = 26). Log linear analysis showed that a diathesis (childhood parasomnia and/or family history of parasomnia) and a stressor (psychologic distress, substance abuse and sleep schedule disorder) predicted the presence of sleepwalking or night terror. Serious violent acts were more likely to occur with males (p < 0.004) who showed sleep schedule disorder (p < 0.03). Both harmful and serious violent sleep behavior occurred with drug abuse (p < 0.009). In comparison to all other groups, those who were violent to other people were males who experienced more stressors (p < 0.02), drank excessive caffeinated beverages, abused drugs (p < 0.03) and showed less stage 4 sleep (p < 0.02) and less alpha (7.5-11 Hz) electroencephalogram NREM sleep (p < 0.02) on polysomnography. Being male and having < 2% stage 4 sleep provided 89% sensitivity, 80% specificity and 81% diagnostic accuracy for individuals who were violent to others. The forensic implications of these findings are discussed.

Adolescent↗

Sleep and EEG disturbances in a rat neurological mutant (taiep) with immobility episodes: a model of narcolepsy-cataplexy.

The electroencephalographic sleep patterns recorded during short periods of time (3 h) of a neurological mutant rat (taiep) were studied. This rat exhibits, among other signs, immobility episodes that are similar to those observed in narcolepsy-cataplexy. We describe findings of long term (6 months) electroencephalographic studies done in 9 mutant and 5 control rats. The mutant rats present electroencephalographic and behavioral disorders consisting of: (a) bursts of cortical waxing and waning waves occurring during the drowsy state; in some animals this activity represents up to 25% of the total drowsiness time; (b) shortened sleep time; (c) fragmented paradoxical sleep; (d) immobility episodes when the animals are subjected to an emotional excitement; and (e) electrographic activity of paradoxical sleep without atonia during the immobility episodes. These findings show that the taiep mutant shows several aspects of narcolepsy-cataplexy and it may represent an experimental model for the study of this pathology.

Animals↗

Clinical neuropharmacology of sleep disorders.

Within the context of the comprehensive treatment of sleep disorders, which includes medical, neurologic, psychiatric, and social interventions, use of medication is often indicated. Among the three benzodiazepine hypnotics that are available in the United States for the treatment of insomnia, flurazepam is effective for both sleep induction and maintenance, and it retains most of its efficacy over a 4-week period of nightly administration; temazepam is effective only for sleep maintenance, and triazolam improves both sleep induction and maintenance with initial but not with continued administration. Rebound phenomena are more frequent and intense with the more rapidly eliminated drug, triazolam, and to a lesser degree with temazepam. Also, with triazolam, certain behavioral side effects, such as amnesia and psychotic-like symptoms, have been reported. With flurazepam, which is a slowly eliminated benzodiazepine, daytime sedation is more frequent than with the other two drugs. When insomnia is secondary to major depression, antidepressant medication should be administered. Methylphenidate, amphetamines, or other stimulant medications are used for the symptomatic treatment of the sleepiness and sleep attacks of narcolepsy and hypersomnia. For cataplexy and the other two auxiliary symptoms of narcolepsy, imipramine or other tricyclics are the drugs of choice. Protriptyline and medroxyprogesterone have been used in treating mild cases of obstructive sleep apnea, but their efficacy is limited. Similarly, for the treatment of central sleep apnea, medroxyprogesterone and acetazolamide have shown only limited effects. Medication for patients with sleepwalking, night terrors, or nightmares should be prescribed judiciously, and primarily when treatment of an underlying psychiatric condition is desired. The neuropharmacology of sleep should also consider drugs that may cause sleep disorders. Medications with sleep disturbing effects include various antihypertensives, bronchodilators, and the energizing antidepressants. Withdrawal of REM-suppressant drugs, such as the barbiturates, may cause nightmares in association with a REM rebound. Occasionally, a drug or a combination of drugs may produce somnambulistic-like activity in some patients.

Antidepressive Agents↗

Development of diagnostic criteria for defining sleep disturbance in Alzheimer's disease.

This article proposes new standards for identifying, defining, and naming sleep/wake cycle disturbances associated with Alzheimer's disease (AD) to aid in more effective research, including the development and testing of potential treatments. Many AD patients develop sleep/wake cycle disturbances associated with distress, depression, and sleep disturbances in the caregiver, as well as early nursing home placement for the patient. The Food and Drug Administration Psychopharmacological Drugs Advisory Committee has emphasized the need for a comprehensive diagnostic system. A key point made by the committee was that behavioral problems associated with dementia (including sleep and chronobiological disturbances) are scientifically and clinically valid targets of pharmacologic treatment. However, current diagnostic criteria preclude development of FDA-acceptable studies of pharmacological interventions because they do not include the required specific indications for treatment. This article attempts to develop better-defined provisional criteria with the goal of promoting epidemiological, physiological, and, especially, pharmacological research on sleep/wake disturbances.

Aged↗

Naps and depression.

In healthy subjects, napping has often been seen as an "abnormal" form of sleep, while sleep has been considered as a necessary feature of life. Social and cultural biases influence the occurrence of napping behavior. However, several observations indicate the presence in man of a two per day modulation of sleep propensity. On the other hand, alterations of nocturnal sleep have been widely described in affective disorders, but little is known about the presence of daytime sleep in depressed patients and the possible effect of daytime sleep episodes on nocturnal sleep. Some attempts to characterize daytime sleep in depression are reviewed. A recent study based on continuous polygraphic recordings indicate that napping occurrence appears to be similar in depressed patients than in control subjects. However, naps structure and organization were different in depressed patients in comparison to controls. Napping seems thus to be more prevalent in depressed patients than previously assumed. Possible effects of naps on mood, alertness in depressed patients remains to be explored.

Depression↗

Forebrain activation in REM sleep: an FDG PET study.

Rapid eye movement (REM) sleep is a behavioral state characterized by cerebral cortical activation with dreaming as an associated behavior. The brainstem mechanisms involved in the generation of REM sleep are well-known, but the forebrain mechanisms that might distinguish it from waking are not well understood. We report here a positron emission tomography (PET) study of regional cerebral glucose utilization in the human forebrain during REM sleep in comparison to waking in six healthy adult females using the 18F-deoxyglucose method. In REM sleep, there is relative activation, shown by increased glucose utilization, in phylogenetically old limbic and paralimbic regions which include the lateral hypothalamic area, amygdaloid complex, septal-ventral striatal areas, and infralimbic, prelimbic, orbitofrontal, cingulate, entorhinal and insular cortices. The largest area of activation is a bilateral, confluent paramedian zone which extends from the septal area into ventral striatum, infralimbic, prelimbic, orbitofrontal and anterior cingulate cortex. There are only small and scattered areas of apparent deactivation. These data suggest that an important function of REM sleep is the integration of neocortical function with basal forebrain-hypothalamic motivational and reward mechanisms. This is in accordance with views that alterations in REM sleep in psychiatric disorders, such as depression, may reflect dysregulation in limbic and paralimbic structures.

Adult↗

A method for the assessment of the functional neuroanatomy of human sleep using FDG PET.

Although sleep is characterized by relative behavioral inactivity, cortical activity is known to cycle in well-defined periods across this state. Cognitive function during sleep has been difficult to define, although disturbances in sleep are known to result from, and to cause, various human pathologies, including neuropsychiatric disorders. Assessment of brain function in humans (related to cognitive operations) during sleep has been limited, until recently, to surface electrophysiologic recordings that limit analysis of regional function, particularly in deep structures. The current report describes one method of assessing human forebrain activation during sleep using the [18F]2-fluoro-2-deoxy-d-glucose ([18F]FDG) method and positron emission tomography (PET) measures of regional cerebral glucose utilization. In comparison with other functional brain imaging techniques (e.g., assessment of blood flow or functional magnetic resonance imaging), this method offers the advantage of a more naturalistic study of sleep since subjects do not have to sleep in a scanning device. This leads to a higher rate of successful completion of studies. The primary disadvantage of this method is the decreased temporal resolution necessitating assessments of global sleep states (e.g., REM or NREM) as opposed to assessing events within a sleep state (e.g., sleep spindles or rapid eye movements).

Electroencephalography↗

Do diagnostic patterns exist in the sleep behaviors of normal children?

We investigated the factor structure of the Children's Sleep Behavior Scale in an unselected sample of children (N = 838), ages 6 to 12.5 years, drawn from an elementary school population. Although no factor emerged that corresponded exactly to the parasomnias, as described by the Association of Sleep Disorders Centers (1979), all of the variables that loaded on Factor 1 were behaviors characteristic of the parasomnias, with the exception of recalled nightmares. Variables that were expected to load on this factor, but did not, were sleeptalking, teeth grinding, and enuresis. Enuresis was not related to any of the sleep behaviors assessed, and teeth grinding shared less than 9% of the variance with any of the other variables. Many of the variables loaded on more than one factor. The second factor, which was labeled bedtime resistance, was the only clearly unambiguous factor. Of the five factors that emerged, the third reflected positive affect, the fourth was a motor factor, and the fifth was an anxiety factor. Nightmares loaded on the anxiety factor as well as the first factor. The results of the study offered no support for the category of Disorders of Initiating and Maintaining sleep (DIMS), which has a childhood onset.

Arousal↗

Randomized clinical trial of supervised tapering and cognitive behavior therapy to facilitate benzodiazepine discontinuation in older adults with chronic insomnia.

OBJECTIVE: This study evaluated the effectiveness of a supervised benzodiazepine taper, singly and combined with cognitive behavior therapy, for benzodiazepine discontinuation in older adults with chronic insomnia. METHOD: Seventy-six older adult outpatients (38 women, 38 men; mean age of 62.5 years) with chronic insomnia and prolonged use (mean duration of 19.3 years) of benzodiazepine medication for sleep were randomly assigned for a 10-week intervention consisting of a supervised benzodiazepine withdrawal program (N=25), cognitive behavior therapy for insomnia (N=24), or supervised withdrawal plus cognitive behavior therapy (N=27). Follow-up assessments were conducted at 3 and 12 months. The main outcome measures were benzodiazepine use, sleep parameters, and anxiety and depressive symptoms. RESULTS: All three interventions produced significant reductions in both the quantity (90% reduction) and frequency (80% reduction) of benzodiazepine use, and 63% of the patients were drug-free within an average of 7 weeks. More patients who received medication taper plus cognitive behavior therapy (85%) were benzodiazepine-free after the initial intervention, compared to those who received medication taper alone (48%) and cognitive behavior therapy alone (54%). The patients in the two groups that received cognitive behavior therapy perceived greater subjective sleep improvements than those who received medication taper alone. Polysomnographic data showed an increase in the amount of time spent in stages 3 and 4 sleep and REM sleep and a decrease in total sleep time across all three conditions from baseline to posttreatment. Initial benzodiazepine reductions were well maintained up to the 12-month follow-up, and sleep improvements became more noticeable over this period. No significant withdrawal symptoms or adverse events were associated with benzodiazepine tapering. CONCLUSIONS: A structured, time-limited intervention is effective in assisting chronic users of benzodiazepine medication to discontinue or reduce their use of medication. The addition of cognitive behavior therapy alleviates insomnia, but sleep improvements may become noticeable only after several months of benzodiazepine abstinence.

Anti-Anxiety Agents↗

Homeostatic, circadian, and emotional regulation of sleep.

A good night's sleep is one of life's most satisfying experiences, while sleeplessness is stressful and causes cognitive impairment. Yet the mechanisms that regulate the ability to sleep have only recently been subjected to detailed investigation. New studies show that the control of wake and sleep emerges from the interaction of cell groups that cause arousal with other nuclei that induce sleep such as the ventrolateral preoptic nucleus (VLPO). The VLPO inhibits the ascending arousal regions and is in turn inhibited by them, thus forming a mutually inhibitory system resembling what electrical engineers call a "flip-flop switch." This switch may help produce sharp transitions between discrete behavioral states, but it is not necessarily stable. The orexin neurons in the lateral hypothalamus may help stabilize this system by exciting arousal regions during wakefulness, preventing unwanted transitions between wakefulness and sleep. The importance of this stabilizing role is apparent in narcolepsy, in which an absence of the orexin neurons causes numerous, unintended transitions in and out of sleep and allows fragments of REM sleep to intrude into wakefulness. These influences on the sleep/wake system by homeostatic and circadian drives, as well as emotional inputs, are reviewed. Understanding the pathways that underlie the regulation of sleep and wakefulness may provide important insights into how the cognitive and emotional systems interact with basic homeostatic and circadian drives for sleep.

Animals↗

The ultimate resignation: suicide and search activity.

This paper presents an integrative approach to suicidal behavior in terms of search activity concept. Search activity concept displays a broad and holistic approach to behavior, adaptation to environment, body resistance, brain amine metabolism, and REM-sleep functions. Search activity is defined as activity that is oriented to change the situation (or at least the subject's attitude to it) in the absence of a precise prediction of the outcome of such activity, but taking into consideration outcomes at all previous stages of activity. According to the proposed hypothesis, renunciation of search (a state opposed to search activity) leads to a feeling of helplessness, problem-solution deficits, inefficient coping, dreams that represent renunciation of search, and a drop in the activity of amines. All these factors further exacerbate the state of renunciation of search and elevate suicidal risk. In addition, the remnants of search activity are misdirected to self-defeating behaviors that increase mental pain and contribute to renunciation of search. This hypothesis integrates findings from a number of fields of study of suicidal behavior, resolves some paradoxes, suggests new lines of research, and raises suggestions for assessment and treatment of suicidal behavior.

Brain Chemistry↗

The association between nocturnal hot flashes and sleep in breast cancer survivors.

This study examined the relationship between objectively measured nocturnal hot flashes and objectively measured sleep in breast cancer survivors with insomnia. Twenty-four women who had completed treatment for non-metastatic breast cancer participated. All were enrolled in a study of cognitive-behavioral treatment for chronic insomnia. Nocturnal hot flashes and sleep were measured by skin conductance and polysomnography, respectively. The 10-minute periods around hot flashes were found to have significantly more wake time, and more stage changes to lighter sleep, than other 10-minute periods during the night. Nights with hot flashes had a significantly higher percentage of wake time, a lower percentage of Stage 2 sleep, and a longer REM latency compared to nights without hot flashes. Overall, hot flashes were found to be associated with less efficient, more disrupted sleep. Nocturnal hot flashes, or their underlying mechanisms, should be considered as potential contributors to sleep disruption in women with breast cancer who report poor sleep.

Adult↗

Pathophysiology and management of insomnia during depression.

Depressed patients often report problems sleeping, and epidemiologic evidence suggests that insomnia may precede the onset of depression. Insomnia is associated with marked impairment in quality of life and ability to function effectively. Many studies have indicated that patients with chronic sleep problems have impaired mood and that effective management of insomnia in depressed patients can markedly improve their depression. Diagnosis of insomnia is challenging because there can be many different causes and the clinical picture can be blurred by the presence of other psychiatric illnesses. Pharmacotherapy provides reliable and rapid relief from insomnia, whereas behavioral therapies help produce long-term improvement. For many years, benzodiazepines have been the mainstay of drug treatment for insomnia. However, these drugs have significant side effects, and tolerance and dependence have discouraged use. Many doctors use sedating antidepressants in low doses to treat chronic insomnia. However, there is little evidence supporting the efficacy of these agents, and many have adverse side effects, including impairment of sleep. The newer selective hypnotic drugs, including the imidazopyridines, may offer patients a better short-term alternative to benzodiazepines or sedating antidepressants.

Anti-Anxiety Agents↗

Effects of intravenous corticotropin-releasing hormone upon sleep-related growth hormone surge and sleep EEG in man.

Corticotropin-releasing hormone (CRH) plays a key role in coordinating neuroendocrine, metabolic and behavioral responses in stress and affective disorders. To further investigate the effects of enhanced pituitary-adrenocortical activity upon sleep-related phenomena we administered four intravenous injections of 50 micrograms human (h)-CRH or saline to 11 normal males at 10 p.m., 11 p.m., 12 p.m. and 1 a.m. and measured plasma levels of cortisol and growth hormone (GH) as well as sleep EEG recordings throughout the night. Treatment with h-CRH resulted in a significant increase of mean (+/- SEM) cortisol secretion between 11 p.m. and 3 a.m. (h-CRH: 100.6 +/- 9.5 ng/ml; saline: 39.0 +/- 1.5 ng/ml; p less than 0.01). This initial cortisol increase after repeated h-CRH stimulations was followed by a period of attenuated plasma cortisol between 3 and 7 a.m. (h-CRH: 70.3 +/- 7.0 ng/ml; saline: 115.5 +/- 8.0 ng/ml; p less than 0.01). Cortisol surges after h-CRH were associated with a significant blunting of sleep-related GH release expressed as areas under concentration curves (h-CRH: 1.245 +/- 0.32 ng/ml/min.10(3); saline: 2.462 +/- 0.92 ng/ml/min.10(3), p less than 0.01). In addition to these hormonal effects, h-CRH induced a decrease of REM and slow wave sleep (stages III and IV) while the amount of more shallow sleep (stages I and II) increased. These effects upon sleep structure were more pronounced during the second part of the night.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Correlation of nocturnal penile tumescence and daytime affect intensity in depressed men.

Although depressed patients have been shown to have diminished nocturnal penile tumescence (NPT), there remains considerable variability of NPT in depression. We hypothesized that affective experience during the day accounts for some of this variability. Forty-five depressed men had assessments of affect intensity and affect balance, NPT, and daytime sexual function, both before and after treatment with Beck's cognitive behavior therapy (CBT). Forty-three normal control subjects were studied for comparison. Daytime affect intensity in depressed men, but not in control subjects, correlated significantly and positively with measures of NPT duration and rigidity both before and after treatment, regardless of the adequacy of daytime sexual function. When the effect of daytime affect on REM activity was controlled, the observed correlations became nonsignificant at pretreatment, but remained significant at posttreatment. Neuropharmacologically mediated changes in arousal responsivity associated with depression may underlie the observed relation between daytime affect intensity, rapid eye movement activity, and NPT.

Adult↗

A clinical picture of child and adolescent narcolepsy.

Although narcolepsy is rarely diagnosed before adulthood, symptoms often begin much earlier and can easily mimic psychiatric disorders in children and adolescents. Clinical experience from a pediatric sleep center is reviewed in 16 consecutive cases of polysomnographically proven narcolepsy with onset of symptoms by age 13 years. Only 1 of the 16 patients presented with the classic clinical tetrad of symptoms (sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis). Behavioral and emotional disturbances were present in 12 of 16 cases, with four patients appearing to have been misdiagnosed with a psychiatric disorder before recognition of the narcolepsy. Obesity appeared as an unexpected association in this case series, with 11 of the 16 narcoleptic patients found to be overweight at the time of diagnosis. The varied clinical presentations, polysomnographic findings, family history, and associated psychiatric symptoms are described. The importance of considering narcolepsy in the differential diagnosis of any child or adolescent with excessive sleepiness is emphasized.

Adolescent↗

Daytime sleepiness in insomnia: behavioral, biological and subjective indices.

We compared three measures of daytime sleepiness, sleep behavior (as measured by the multiple sleep latency test), a biological index of sleepiness (pupillometry) and subjective sleepiness (as measured by the Stanford Sleepiness Scale), in evaluating middle-aged individuals with psychophysiological insomnia (n = 20) or no sleep problem (n = 20). Subjects underwent polysomnography (PSG) and four multiple sleep latency test/pupillometry trials the following day. The results determined that neither behavioral, biological nor subjective indices distinguished these two groups. Differentiating the insomniacs into true insomniac (n = 14) and normal sleeping insomniac (insomniacs with sleep efficiency greater than 90%, n = 6) subgroups based upon PSG did not improve daytime discriminations. Furthermore, nighttime sleep experience, measured by either PSG or self-report, was not a strong predictor of these daytime indices among either insomniacs or noninsomniacs. The results of this study support the conclusions that insomniacs do not exhibit heightened levels of daytime sleepiness and that routine fluctuations in sleep exert minimal influence on daytime sleepiness among insomniacs and noninsomniacs. The former finding is likely due either to insomniacs satisfying their biological sleep need despite poor sleep or chronic physiological hyperarousal preventing both sleep and sleepiness.

Adult↗