The Persistent Paradox of Rapid Eye Movement Sleep (REMS): Brain Waves and Dreaming.

The original conceptualization of REM sleep as paradoxical sleep was based on its EEG resembling wakefulness and its association with dreaming. Over time, the concept of paradox was expanded to include various associations with REM sleep, such as dream exclusivity, high recall, and pathophysiology. However, none of these associations are unique to REM sleep; they can also occur in other sleep states. Today, after more than fifty years of focused research, two aspects of REMS clearly retain paradoxical exclusivity. Despite the persistent contention that the EEG of human REMS consists of wake-like, low-voltage, non-synchronous electrical discharges, REMS is based on and defined by the intracranial electrical presence of 5-8 Hz. theta, which has always been the marker of REMS in other animals. The wake-like EEG used to define REMS on human polysomnography is secondary to a generalized absence of electrophysiological waveforms because the strong waves of intracranial theta do not propagate to scalp electrodes placed outside the skull. It is a persistent paradox that the theta frequency is restricted to a cyclical intracranial dynamic that does not extend beyond the lining of the brain. REMS has a persistent association with narratively long and salient dream reports. However, the extension of this finding to equate REMS with dreaming led to a foundational error in neuroscientific logic. Major theories and clinical approaches were built upon this belief despite clear evidence that dreaming is reported throughout sleep in definingly different physiologic and phenomenological forms. Few studies have addressed the differences between the dreams reported from the different stages of sleep so that today, the most paradoxical aspect of REMS dreaming may be how little the state has actually been studied. An assessment of the differences in dreaming between sleep stages could provide valuable insights into how dreaming relates to the underlying brain activity and physiological processes occurring during each stage. The brain waves and dreams of REMS persist as being paradoxically unique and different from waking and the other states of sleep consciousness.

Drug-Induced Hypersomnolence.

Daytime somnolence is among the most commonly reported drug side effects. The United States has the highest rate of motor vehicular accident (MVA) deaths with sedating drug use a factor in more than 30%. Sedating drug use extends beyond drugs of abuse to sedating medications. This paper presents pharmacodynamics, performance and driving tests, and MVAs for somnolence inducing agents classified as hypnotics, sedatives, and/or sedation as a side effect. This classification, based on the drug tendency to induce next-day sedation after nighttime use, can be cogently used by prescribers, pharmacists, regulatory agencies, and in direct to consumer marketing.

The effects of altitude associated central apnea on the diagnosis and treatment of obstructive sleep apnea: comparative data from three different altitude locations in the mountain west.

STUDY OBJECTIVES: This study documents both the incidence and effects of central apnea on diagnosis and treatment of OSA at different altitudes in the Mountain West and substantiates the clinical impression that individuals living at altitude with moderate to severe OSA are significantly more difficult to treat with PAP. METHODS: Split-night polysomnography was compared between sites for patients with a diagnostic AHI > 15 living at 1421 meters (Site 1; N = 150), at 1808 m (Site 2; N = 150) and at 2165 m (Site 3; N = 142). The quality of PAP titration obtained was rated, based on AASM clinical guidelines, from 1 = optimal to 4 = unacceptable. Patients developing central apneas during PAP therapy (CAI > 5.0) were titrated with an alternative O(2) > CPAP/Bilevel PAP protocol. RESULTS: The mean number of central apneas in the diagnostic portion of studies was significantly higher (p < 0.01) at Sites 2 (19.26) and 3 (12.36) than at Site 1 (3.11). Mean numbers of central apneas/h developing on treatment with PAP varied from 4.8/h at Site 1, to 9.79/h at Site 2, to 19.25/h at Site 3 (p < 0.001). At Site 1, 10.6% had a central apnea index (CAI) > 5.0, while 22% met this criterion at Site 2 and 38.7% at Site 3 (Site 3 vs Site 1, p = 0.01; Site 2 vs Site 1, p = 0.02). Rated titration quality varied significantly between sites. At Site 1, mean titration quality was 1.437 (SD 0.821); for Site 2, 1.569 (SD 0.96), and for Site 3, 1.772 (SD 1.025). Titration quality at Site 3 was significantly worse than at Site 1 (t = 3.22, p < 0.01) and at Site 2 (t = 2.55, p < 0.02). Repeat titration requirement differed significantly (p = 0.025). Analysis of covariance comparing titration across 3 altitude levels, controlling for age, was significant for the effect of altitude (p = 0.017). Utilizing the alternative O(2) > C-PAP/Bi-PAP protocol in patients with CAI > 5.0 developing on PAP treatment, an overall optimal or good titration (AASM criteria) was attained in 75/79 (95%) of titrated patients. CONCLUSIONS: This study demonstrates that central apnea becomes significantly more common at increasing altitude in both diagnostic and treatment portions of split-night polysomnography in patients with significant OSA. An apparent exponential increase in the percentage of OSA patients with a CAI > 5.0 occurs with increasing altitude. Altitude associated central apnea has a significant negative effect on the quality of OSA treatment obtained during PAP titration for patients living at the altitudes addressed in this study.

The nightmares of sleep apnea: nightmare frequency declines with increasing apnea hypopnea index.

OBJECTIVE: To clarify the association of reported nightmare recall with polysomnographically defined obstructive sleep apnea (OSA) in a sleep laboratory population. METHODS: This study included 393 individuals undergoing clinical polysomnography including a general intake questionnaire with questions on dream and nightmare recall frequency. Mean age was 50.5 and a range of 13 to 82 years, with 33% of the sample female and 67% male. Reported dream and nightmare recall were classified as infrequent when reported at less than once a month, or frequent when reported at a frequency greater than once per week. RESULTS: Mean Apnea-hypopnea Index AHI was 34.9 (std. 32.0) indicating a high frequency of severe (AHI > 30) OSA in this clinical study population. Both AHI and Apnea Index (AI) were significantly higher (p = 0.000) for the grouping reporting infrequent nightmare recall. As the AHI score increased, the percent of participants with frequent nightmare recall decreased linearly. CONCLUSION: Patients with higher AHI report a lower nightmare frequency, indicating that significant OSA suppresses the cognitive experience of nightmare recall. Depressed nightmare recall may occur secondary to the REMS suppression know to occur in patients with significant OSA.

Excessive daytime sleepiness.

Excessive daytime sleepiness is one of the most common sleep-related patient symptoms, and it affects an estimated 20 percent of the population. Persons with excessive daytime sleepiness are at risk of motor vehicle and work-related incidents, and have poorer health than comparable adults. The most common causes of excessive daytime sleepiness are sleep deprivation, obstructive sleep apnea, and sedating medications. Other potential causes of excessive daytime sleepiness include certain medical and psychiatric conditions and sleep disorders, such as narcolepsy. Obstructive sleep apnea is a particularly significant cause of excessive daytime sleepiness. An estimated 26 to 32 percent of adults are at risk of or have obstructive sleep apnea, and the prevalence is expected to increase. The evaluation and management of excessive daytime sleepiness is based on the identification and treatment of underlying conditions (particularly obstructive sleep apnea), and the appropriate use of activating medications.

Obstructive sleep apnea (OSA) in primary care: evidence-based practice.

This paper presents data evidence supporting the value of diagnosing and treating obstructive sleep apnea (OSA) in reducing morbidity and mortality, improving comorbid disease processes, and improving patient quality of life. These data are derived from a PubMed-based meta-analysis of recent cost effectiveness, standards of practice, and epidemiological studies of OSA, which are ranked using a hierarchical strength of recommendation taxonomy. Cost and health care utilization data have been calculated for OSA and hypersomnolence as well as for diagnostic testing. Strong evidence (which is indicated by a strength of recommendation rating of "A") exists for the association of adult OSA with obesity, daytime sleepiness, hypertension, and motor vehicular accidents. Strong evidence also exists for requiring full-night or split-night attended polysomnography (PSG) for the diagnosis and treatment of adult OSA and for patients with systolic or diastolic heart failure not responding to optimal medical management. Good evidence (B) exists for the association of adult OSA with congestive heart failure, coronary artery disease, cerebral vascular accidents, metabolic syndrome, and increased mortality. Good evidence also exists to indicate that the nonattended PSG can be used to diagnose sleep breathing disorders, that autotitration systems can be used to titrate continuous positive airway pressure (CPAP) therapy, and that the multiple sleep latency test can be used in the assessment of daytime sleepiness.

Medications and their effects on sleep.

Only a few years ago, if patients complained of difficulty sleeping,medications that were often dangerous and addictive were prescribed to induce sleep, and the basis of the patient's complaint was not addressed. Now sleeping pills are safer, and our understanding of the sleep state has increased exponentially. Insomnia and daytime sleepiness are no longer diagnoses; they are complaints needing to be addressed-symptoms of a spectrum of sleep disorders with specific diagnostic criteria and appropriate treatments.

Obstructive sleep apnea in sleepy pediatric psychiatry clinic patients: polysomnographic and clinical correlates.

STUDY OBJECTIVES: To assess the incidence of polysomnographically defined obstructive sleep apnea (OSA) in pediatric psychiatric clinic patients reporting daytime sleepiness on questionnaire, and to identify diagnostic correlates for OSA in this grouping. DESIGN: Prospective and observational. SETTING: Outpatient pediatric psychiatry clinic, outpatient sleep medicine clinic, AASM-accredited hospital-based sleep laboratory. SUBJECTS: Children aged 3 to 16 years, reporting daytime sleepiness on questionnaire (N = 74); exclusions: adenotonsillectomy and trisomy 21. INTERVENTIONS: Parents and children completed a questionnaire designed and validated for identifying pediatric patients with OSA at the pediatric psychiatry clinic. Patients with at least one positive response as to daytime sleepiness (N = 74) were referred for a history and physical by a board-certified sleep medicine physician before in-hospital polysomnography utilizing a routine apnea montage with parent or legal guardian sleeping in room. RESULTS: Mean apnea-hypopnea index (AHI) for this pediatric psychiatry clinic grouping was 5.5. Of these patients, 39.2% had an AHI > 5.0. Mean AHI for patients with attention deficit/hyperactivity disorder (AD/HD) was 7.1; without AD/HD it was 4.5 (p < 0.05). Mean AHI for patients with tonsillar hypertrophy was 6.5 compared with 4.4 for those without tonsillar hypertrophy (p < 0.05). CONCLUSION: In a clinical grouping of pediatric psychiatry patients reporting daytime sleepiness by questionnaire, polysomnographically defined OSA is common. Both AD/HD as diagnosed using DSM-IV criteria and tonsillar hypertrophy based on clinical exam by a sleep medicine physician are diagnostic correlates for polysomnographically defined OSA in this pediatric psychiatry clinic grouping of patients.

Non-dreamers.

OBJECTIVE: Assess incidence and clarify whether diagnostic correlates exist for sleep laboratory patients reporting a lack of dream recall. To awaken, during polysomnographically defined sleep including rapid eye movement (REM) sleep, individuals reporting never having experienced a dream, and determine whether they report dreaming. METHODS: Study # 1 - Incidence and polysomnographic correlates of sleep lab patients responding on questionnaire that they had never experienced dreaming. Study # 2 - Phone interviews with those individuals reporting non-dreaming on questionnaire to reassess incidence. Study # 3 - After reassessment, individuals (non-dreamers - # 16) are awakened during polysomnographic defined sleep (including REM sleep) and queried about dream recall. This group is compared statistically to a group (rare-dreamers - # 12) that reported dreaming as an extremely rare occurrence (mean dream recall latency - 13.5 years). RESULTS: Study # 1: Incidence of questionnaire reported non-dreaming in this sleep laboratory population is 6.5% (N=534) and is associated with the diagnosis of obstructive sleep apnea (specificity 95.6% for respiratory disturbance index >15). Study # 2 - Individuals who report after interview to have never experienced dreaming are more unusual (0.38% of this sleep laboratory population). Study # 3 - None of the non-dreamers (# 16) reported dream recall after waking in the sleep laboratory (36 awakenings in total for this group). This group does not differ, based on polysomnographic, clinical, or demographic variables, from the rare-dreaming group that occasionally reported dreams when awakened (3/12 patients, 3/32 awakenings) - a finding consistent with the reports of previous studies. CONCLUSION: The experience of dreaming may not be as ubiquitous as generally accepted. The group of non-dreamers evaluated in this study reports never having recalled a dream and reports no dreams when awakened during polysomnographicly defined sleep. These individuals might not experience dreaming.

Drug induced nightmares--an etiology based review.

OBJECTIVE: Recent clinical trials have included patient complaints of nightmares as a category of reportable medication side effects. This study integrates that data into current experimental and theoretical research of drug effects that may alter dreaming and nightmares. The objective is to provide a clinical and theoretical framework useful in categorizing the potential and reported drug effects on nightmares. METHODOLOGY: This study reviews case reports and clinical trials that have reported nightmares or alterations in dreaming occurring secondary to medication usage. These data are analysed as to the probability of the drug/nightmare association, and integrated into current electrophysiological and neurochemical theories of dreaming and nightmares. RESULTS: Pharmacological agents affecting the neurotransmitters norepinephrine, serotonin and dopamine are clearly associated with patient reports of nightmares. Agents affecting immunological response to infectious disease are likely to induce nightmares in some patients. A possible association exists between reports of nightmares and agents affecting the neurotransmitters acetylcholine, GABA and histamine, as well as for some anesthetics, antipsychotics and antiepileptic agents. CONCLUSION: By utilizing our current experimental and theoretical knowledge base, the potential etiology of a majority of reported drug effects on nightmares can be classified. These data support current neurochemical theories of dreaming, as well as suggesting that the biochemical basis for dreaming and nightmare induction may be more complex than generally suggested.

Medication effects on sleep.

Each person spends one third of his or her life asleep. It is not surprising that such a complex and pervasive cognitive state should be affected by drugs in many different ways. A philosophy that remains cogent for the CNS is that new research almost always shows this system to be more complex than previously thought. Only a few years ago, if patients complained of difficulty sleeping, they were given pills, often dangerous and addictive pills, to induce sleep no matter what the basis of the complaint might be. Sleeping pills may be safer now, and the understanding of the sleep state itself has increased rapidly. Diagnoses are still diffuse, however, and treatments are often poorly directed. Depression is the offspring of the phlegmatic disposition and the melancholia of another era. Clinically, diagnosis is based on a global assessment of symptoms. It is likely that a diagnosis of depression may include a spectrum of underlying diseases that cannot now be clinically differentiated. Medications have multiple effects on sleep and have many side effects. Progress has, however, been made beyond mother's little pills. Insomnia is no longer a diagnosis but a complaint to be addressed--a symptom of 1 of 60 potential sleep disorders. Each of these disorders has specific and appropriate treatments.

Medications for the Treatment of Sleep Disorders: An Overview.

Sleep disorders can be divided into those producing insomnia, those causing daytime sleepiness, and those disrupting sleep. Transient insomnia is extremely common, afflicting up to 80% of the population. Chronic insomnia affects 15% of the population. Benzodiazepines are frequently used to treat insomnia; however, there may be a withdrawal syndrome with rapid eye movement (REM) rebound. Two newer benzodiazepine-like agents, zolpidem and zaleplon, have fewer side effects, yet good efficacy. Other agents for insomnia include sedating antidepressants and over-the-counter sleep products (sedating antihistamines). Nonpharmacologic behavioral methods may also have therapeutic benefit. An understanding of the electrophysiologic and neurochemical correlates of the stages of sleep is useful in defining and understanding sleep disorders. Excessive daytime sleepiness is often associated with obstructive sleep apnea or depression. Medications, including amphetamines, may be used to induce daytime alertness. Parasomnias include disorders of arousal and of REM sleep. Chronic medical illnesses can become symptomatic during specific sleep stages. Many medications affect sleep stages and can thus cause sleep disorders or exacerbate the effect of chronic illnesses on sleep. Conversely, medications may be used therapeutically for specific sleep disorders. For example, restless legs syndrome and periodic limb movement disorder may be treated with dopamine agonists. An understanding of the disorders of sleep and the effects of medications is required for the appropriate use of medications affecting sleep.

Nightmares and disorders of dreaming.

Dreams occur during all stages of sleep. Nightmares are common. They can be associated with poor sleep and diminished daytime performance. Frequent nightmares are not related to underlying psychopathology in most children and in some "creative" adults. However, recurrent nightmares are the most defining symptom of post-traumatic stress disorder and may be associated with other psychiatric illnesses. Night terrors are arousal disorders that occur most often in children and usually occur early in the sleep period. Patients with rapid-eye-movement behavior disorder often present with nocturnal injury resulting from the acting out of dreams. Dream disorders may respond to medication, but behavioral treatment approaches have shown excellent results, particularly in patients with post-traumatic stress disorder and recurrent nightmares.

Treatment of insomnia.

Recent research in sleep disorders has led to a better understanding of the causes and treatment of insomnia. A clearer understanding of the actions and side effects of sedative-hypnotic medications has led to a decrease in their use. Treatment of insomnia should be based on the following principles: (1) referral of individuals who are dangerous to themselves or others, (2) active treatment of psychiatric illness, (3) treatment of underlying disease, (4) use of nondrug treatment modalities and (5) restriction of the use of hypnotics to the treatment of transient insomnia.

Cross-cultural dream use in Hawaii.

Cultural variations in the narrative content of dreams have been reported in many studies. This basic cultural difference in dream language and representations has been used to support psychoanalytic theories of dreaming, especially that of the Jungian-based schools. Others have postulated that such variations reflect the cultural differences that each individual experiences during waking life. This "continuity" hypothesis proposes that a high correlation exists between an individual's waking life and his or her dream content. The biologic framework of dreams, sleep/dream-state physiology, is cross-culturally consistent, and the incidence of dream related pathology also is remarkedly similar between differing cultures.

Nightmares.

Although sporadic nightmares may be normal responses to stress, chronic nightmares can be troublesome. Nightmare syndrome involves dreams during REM sleep and is associated with abnormal psychologic tests and psychiatric disorders. Night terrors are most common in childhood, occur during deep sleep and rarely reflect underlying pathology. Post-traumatic stress disorder produces recurrent and repetitive nightmares. The onset of nightmares in an adult is often associated with medication or illness.

Diagnosis and treatment of insomnia.

Insomnia is a disorder of initiation and maintenance of sleep that results in daytime somnolence. The differential diagnosis of the various forms of insomnia is based primarily on the history, including information from the sleeping partner. The possibility of underlying depression or sleep apnea must be given consideration in every patient with insomnia, because inappropriate therapy may be dangerous in these instances. In general, the benzodiazepines have supplanted the traditional hypnotics in the treatment of insomnia.

Sleep disorders and insomnia.

Primary sleep disorders include narcolepsy, the Pickwickian syndrome, sleep apnea in infants and other rare conditions. Secondary sleep disorders occur in depression, alcoholism, endocrinopathies, heart failure and pregnancy. Medical symptomatology often increases during rapid-eye-movement (REM) sleep, when physiologic activity is high. Insomnia, the most common sleep disorder, requires careful work-up, attempts at environmental manipulation and judicious short-term pharmacotherapy. Pharmacologic manipulation of sleep is beset with complications. A basic understanding of properties and side effects of the sleep-inducing drugs is needed in order to select the optimal agent.