National Sleep Disorders Research Plan
 
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Section 5 Content:
Sleep in Psychiatric, Alcohol and Substance Use Disorders
Immunomodulation, Neuroendocrinology and Sleep    
Sleep-Disordered Breathing
Insomnia  
Narcolepsy and Other Hypersomnias
Restless Legs Syndrome/Periodic Limb Movement Disorders
Sleep in Other Neurological Disorders
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 








SECTION 5 - SLEEP DISORDERS

Parasomnias


Adult

Background

Parasomnias are undesirable behavioral, autonomic nervous system, or experiential phenomena during sleep, usually characterized by increased motor and/or autonomic activity, sleep-wake state dissociation, altered responsiveness to the environment, and retrograde amnesia. Specific parasomnias arise during sleep-wake transitions, NREM sleep, or REM sleep and are often divided into two groups. Primary parasomnias are disorders of sleep states per se, and secondary parasomnias are disorders of other organ systems that arise during sleep. Virtually all primary parasomnias represent an admixture or simultaneous occurrence of elements of both wakefulness and sleep

The most common primary parasomnias are disorders of arousal and REM sleep disorders. Disorders of arousal include confusional arousals, sleepwalking, and sleep terrors, all characterized by partial arousals from NREM sleep. REM sleep parasomnias include nightmares, characterized by frightening dreams and autonomic arousal, and REM behavior disorder (RBD), characterized by absence of the muscle atonia normally present during REM sleep. The behaviors associated with primary parasomnias may lead to injury of the patient or bed partner, and may have forensic implications.

Numerous secondary parasomnias, such as sleep-related expiratory groaning, or esophageal spasm, have been reported. Typically, descriptions have been provided for single cases or very small case series, making scientific evaluation difficult. These phenomena are likely to be quite common, but are often unrecognized, misdiagnosed, or ignored in clinical practice. The pathophysiology, morbidity, and functional consequences of secondary parasomnias are unknown.

Progress In The Last 5 Years

- Epidemiological studies have shown that disorders of arousal occur in about 10% of adults, and are usually not associated with significant underlying psychiatric or psychological disorders. These disorders are very common in children, but may begin during adulthood or persist into adulthood or. There is growing evidence for genetic determinants of these disorders of arousal.

- Exogenous triggers have been identified for disorders of arousal in predisposed individuals. These include sleep deprivation, alcohol ingestion, and medications.

- The basic sleep architecture and sleep macrostructure is normal in patients with disorders of arousal. "Hypersynchronous delta" activity has not been substantiated as an EEG marker for disorders of arousal. However, quantitative EEG analyses in patients with disorders of arousal indicate instability of slow wave sleep, particularly during the first slow-wave sleep period of the night. This instability may be related to cyclic alternating pattern.

- RBD, which may have a prevalence as high as 0.5%, has two striking demographic features: 90% of affected individuals are male, and most cases begin after 50 years of age. Clonazepam is efficacious in 90% of cases.

- At least 50% of RBD cases are related to recognized neurologic conditions, particularly narcolepsy and the synucleinopathies (Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies). RBD may precede the appearance of other features of the underlying disease by as many as 10 years. RBD may also be iatrogenic, due primarily to medications such as selective serotonin reuptake inhibitors (SSRIs).

- Functional neuroimaging studies have documented reduced dopamine transporters and decreased dopaminergic innervation of the basal ganglia in patients with RBD.

- Other conditions characterized by sleep-wake state dissociations have been identified, and may be related to RBD. These include parasomnia overlap syndrome, agrypnia excitata, and status dissociatus.

Research Recommendations

- Better define the pathophysiology and neuroanatomic substrates of primary parasomnias in human and animal studies. In humans, specific methods could include functional neuroimaging and quantitative EEG studies (e.g., investigations of cyclic alternating pattern in disorders of arousal). Psychophysiological and neurophysiological studies could help to identify factors that trigger and maintain chronic parasomnias. A brain bank for RBD and other parasomnias would be particularly useful to study their structural and genetic origins. The identification of genetic and environmental factors involved in the etiology and pathogenesis of primary parasomnias may be facilitated by the presence of distinctive phenotypes for these disorders. Animal models for parasomnias could involve techniques such as genetic manipulations, brain lesions and brain stimulation, sleep deprivation and other behavioral provocation techniques, and pharmacologic manipulations. In particular, animal studies investigating motor control and sleep could help to further elucidate the pathophysiology of parasomnias.

- Investigate pharmacologic and behavioral treatments for primary and secondary parasomnias in clinical trials. Intervention studies could help to identify both common and distinctive mechanisms of action for different treatments in different disorders.

- Further define the relationships between the different parasomnias, and between parasomnias and other neurological disorders. For instance, the relationship between disorders of arousal and nocturnal seizures, particularly nocturnal frontal lobe epilepsy, should be further investigated. Relationships between RBD, neuropsychiatric disorders, and specific medications need to be better defined.

- Obtain clinical and physiological information regarding secondary parasomnias as a first step toward identifying the prevalence, etiology, and efficacious treatment of these disorders.

Pediatric

Background

Although parasomnias are among the most common clinical sleep disturbances experienced in childhood, little is known about the underlying neurophysiologic mechanisms and neurotransmitter systems responsible for their development and relative importance.

Although there is a genetic predisposition for many parasomnias, the specific genes involved have yet to be identified, and little is known about the interaction between genetic phenotype, other aspects of sleep physiology such as arousal threshold, and sleep inertia and environmental factors. Treatment strategies involving pharmacologic and behavioral interventions have been developed, but most outcome studies have included very small sample sizes and short-term follow-up.

Progress In The Last 5 Years

- Several studies have reported an association between partial arousal parasomnias and both migraine headaches and Tourette's syndrome in children, raising the possibility that serotonergic pathways may be involved. Case reports of novel treatment strategies for partial arousal parasomnias have suggested that behavioral interventions such as scheduled awakenings and hypnotherapy may be effective non-pharmacologic treatment options, but little is known about the underlying mechanism responsible for the clinical response.

Research Recommendations

- Examine interactions between the developing central nervous system, genetics, other aspects of sleep physiology, and environmental factors in determining phenotypic expression of partial arousal parasomnias in childhood.

- Examine the role of various neurotransmitter systems in the neurophysiology of partial arousal parasomnias.

- Evaluate the efficacy of, and underlying mechanisms for, pharmacologic and non-pharmacologic treatment strategies for partial arousal parasomnias and rhythmic movement disorders in childhood.

 
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