Background
Rapid eye movement (REM) sleep behavior disorder (RBD) is a sleep disorder characterized by the loss of normal voluntary muscle atonia during REM sleep, in association with complex motor behavior while dreaming. [1, 2, 3, 4]
Diagnostic Criteria (DSM-5 and ICSD-2)
The specific DSM-5 criteria for rapid eye movement sleep behavior disorder are as follows: [5]
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Recurrent episodes of arousal during sleep associated with vocalization and/or complex motor behaviors that arise during rapid eye movement (REM) sleep
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On waking from these episodes, the individual is not confused or disoriented and is completely alert
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Either of the following is present: REM sleep without atonia on polysomnographic recordings; or a history suggestive of REM sleep behavior disorder and an established synucleinopathy diagnosis (e.g., Parkinson’s disease, multiple system atrophy)
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The episodes cause significant distress or impairment in social, occupational or other areas of functioning which may include serious injury to self or the bed partner
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The disturbance cannot be explained by the effects of a drug of abuse or medication
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The episodes cannot be attributed to another mental disorder or medical condition
The International Classification of Sleep Disorders requires the following criteria for the clinical diagnosis of RBD: [6]
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Presence of REM sleep without atonia (RSWA) on polysomnography (PSG)
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The presence of at least one of the following conditions: (1) sleep-related behaviors, by history, that have been injurious, potentially injurious, or disruptive (e.g., dream enactment behavior); (2) abnormal REM sleep behavior documented during PSG monitoring
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Absence of epileptiform activity on electroencephalogram (EEG) during REM sleep (unless RBD can be clearly distinguished from any concurrent REM sleep-related seizure disorder)
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Sleep disorder not better explained by another sleep disorder, a medical or neurologic disorder, a mental disorder, medication use, or a substance use disorder
Etiology
The precise etiology and neural structures involved in RBD are unknown. Based on animal (cats, rats), lesional, and neuropathologic studies, sleep-regulating nuclei, particularly the pontine tegmentum, are thought to be involved in the pathogenesis of RBD. Also, a complex interplay of various neurochemical systems, such as the noradrenergic, cholinergic, and serotonergic systems, seems to exist in the pathogenesis of the condition. [1, 7]
Normally, generalized atonia of skeletal muscles occurs during REM sleep. This atonia results from active inhibition of the final common pathway of spinal motor neurons by way of the medullary magnocellular reticular formation (MCRF); this suppresses anterior horn cell activity via projections of the ventral lateral reticulospinal tract.
Various pontine nuclei are known to influence the REM and non-REM sleep circuits, including the locus coeruleus(LC), pedunculopontine nucleus (PPN), and laterodorsal tegmental nucleus (LDTN). [8] In addition, forebrain cortical and subcortical structures and the substantia nigra, thalamus, hypothalamus, basal forebrain, and frontal cortex are also involved. However, their precise roles are unknown.
Idiopathic RBD
RBD may be idiopathic. However, several studies have suggested that idiopathic RBD is a potential marker for the later development of neurodegenerative disorders characterized by alpha-synuclein deposition. These include Parkinson disease, multiple system atrophy, dementia with Lewy bodies, and pure autonomic failure, with the risk varying among different studies. (RBD is less frequently associated with nonsynucleinopathies.) [1, 2, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18]
In fact, studies have suggested that RBD may be associated with alpha-synuclein–mediated degeneration of sleep-regulating nuclei in the brainstem, particularly the pontine tegmentum.
In essence, RBD may be the prodrome of neurodegenerative disease, such as diffuse Lew body (DLB) disease or Parkinson disease. [1, 19] In experimental studies in cats, bilateral pontine lesions resulted in a persistent absence of REM atonia associated with prominent motor activity during REM sleep similar to that observed in RBD in humans.
Studies by Eisensehr et al using iodine 123 (123 I) immunoperoxidase technique (IPT) single photon-emission computed tomography (SPECT) scanning demonstrated that striatal presynaptic dopamine transporters are reduced in idiopathic RBD. [20]
Studies by Fantini et al demonstrated impairment of cortical activity in idiopathic RBD, particularly in the occipital region during both wakefulness and REM sleep, compared with controls. [21] Results were similar to those of functional studies, such as of the perfusion and metabolic impairment pattern, observed in DLB disease and in Parkinson disease. Similar cortical activity in the frontal and temporal regions was impaired only during wakefulness.
Research evidence suggests, therefore, that many cases of idiopathic RBD may not be truly idiopathic, leading some to suggest the term cryptogenic rather than idiopathic. [22]
Secondary RBD
In addition, RBD may occur in association with various neurologic conditions (ie, secondary RBD), including vascular lesions, brainstem neoplasms, demyelinating disease, autoimmune/inflammatory disorders, and neurodegenerative disorders.
Genetics
Nightingale et al suggested in a study that 36% of persons with narcolepsy experience symptoms of RBD. [23] This link led to the identification of a strong association of RBD with HLA class II genes. [24, 25, 26]
Epidemiology
According to DSM-5, the prevalence of REM sleep behavior disorder is approximately 0.38%–0.5% in the general population. Prevalence in patients with psychiatric disorders is greater, possibly related to medications prescribed for psychiatric disorders. [5]
RBD occurs predominantly in males. [27] In a report by Olson et al involving 93 patients with RBD, only 12 patients (13%) were female. [4]
Typically, RBD is a disease of elderly persons. [9] The risk increases after the sixth decade, although the disease may occur at any age, including in childhood. [27]
Prognosis
The prognosis of RBD depends on its etiology. In idiopathic cases, the symptoms are controlled with medications. In secondary cases, the prognosis depends on the underlying primary disease.
No deaths have been reported in idiopathic cases of RBD; however, patients and bed partners may experience serious injury. [28] In the reported cases, 32% of patients had injured themselves and 64% had assaulted their spouse. [4] Subdural hematomas occurred in two patients. [4] In secondary cases, the morbidity and mortality rates depend on the underlying disease itself.
Mortality/morbidity
REM sleep disorder is present concurrently in approximately 30% of patients with narcolepsy. When comorbid with narcolepsy, RBD presents in younger patients with equal frequency in males and females. [5] Based on findings from sleep studies, most individuals (50%) with initially “idiopathic” RBD will eventually develop a neurodegenerative disease, most notably, one of the synucleinopathies (e.g., Parkinson disease, multiple system atrophy, dementia with Lewy bodies). REM sleep behavior disorder often predates any other sign of these disorders by many years (often more than a decade).
Patient Education
Educate the patient and his or her bed partner for environmental safety. Potentially dangerous objects should be removed from the bedroom, and the mattress should be placed on the floor or a cushion placed around the bed. (See Treatment.)
For patient education information, see the Sleep Disorders Center, as well as REM Sleep Behavior Disorder, Disorders That Disrupt Sleep (Parasomnias), and Sleep Disorders and Aging.
