In 1817, James Parkinson wrote “An Essay on the Shaking Palsy” [1]. This first comprehensive description of the disorder that would later bear his name noted that “sleep becomes much disturbed” in patients and hinted at a disorder of agitated dream enactment.

His (Case VI) attendants observed, that of late the trembling would sometimes begin in his sleep, and increase until it awakened him: when he always was in a state of agitation and alarm.

…when exhausted nature seizes a small portion of sleep, the motion becomes so violent as not only to shake the bed-hangings, but even the floor and sashes of the room.

Prior to Parkinson’s monograph, episodes of dream enactment suggestive of RBD were reported as early by Hippocrates (circa 460–370 BCE), Aristotle (384–322 BCE), and Galen (circa 129–200) and later by Cervantes (1547–1616). By the Renaissance, dream enactment was considered a window into subconscious psychological conflict. In William Shakespeare’s Macbeth, the sleepwalking Lady Macbeth admits to being a coconspirator in murder and reveals her subsequent internal torment.

Out damned spot! Out, I say! …What, will these hands never be clean?

Soon after Aserinsky and Kleitman discovered regularly occurring periods of eye motility during sleep in 1953 [2], investigators began to explore the brainstem mechanisms of REM sleep, including those leading to skeletal muscle paralysis. In 1965, experimental lesions of pontine regions by Jouvet adjacent to the locus coeruleus in cats caused an absence of the expected atonia. These cats demonstrated prominent motor behaviors during REM sleep suspected to be dream mentation (“oneirism”) [3].

In 1982, Schenck and Mahowald evaluated a 67-year-old man who presented with a history of violent dream-enactment behavior (DEB). A subsequent polysomnogram demonstrated REM sleep without atonia along with vigorous DEB. In 1986, they published a series of patients and named the condition “REM sleep behavior disorder.” By 1996, 38 % of their original series of patients had developed a parkinsonian syndrome and by 2013 the conversion rate reached 81 % [4].

Prior to developing bradykinesia, cogwheel rigidity, and tremor, many Parkinson’s disease (PD) patients will describe a parasomnia or abnormal nocturnal behavior emanating from sleep. The sleep-related movements appear purposeful as if the patient is acting out some internal dream plot and when awoken, vivid dreams are described. The condition typically presents in a middle-aged individual without a history of sleepwalking or other parasomnia. The frequency of incidents ranges from once every few months to multiple nightly episodes. Often, there is a prolonged prodrome lasting years with progressively more prominent nocturnal behaviors occurring over time [5, 6].

The spectrum of dream-enactment behavior (DEB) in RBD varies from small hand movements to violent activities such as punching, kicking, or leaping out of bed. Examples of sleep-related injuries include subdural hematoma, shoulder dislocation, cervical fracture, as well as lacerations severing tendons, arteries, and nerves. As bed partners are frequently the target of violent dream enactment, RBD may have forensic implications, with patients wrongly in the criminal justice system [5, 6].

Patients manifest DEB more often during the second half of the night and sleep-related injury (SRI) is more likely to occur in later REM periods. This is related to the progressive increase in phasic activity, frequency, and duration of REM sleep normally seen throughout a night of sleep.

Importantly, RBD patients may not have more violent dreams than normal individuals. Instead, they merely act them out. Sleep-related vocalizations may be loud and frequently laden with expletives. This is most often discordant from waking personality, and RBD patients do not demonstrate greater daytime aggressiveness.

Patients and families may adopt extraordinary measures to prevent SRI: placing obstacles to hinder exiting the bed or sleeping on a floor mattress in a room devoid of furniture. Prolonged diagnostic delay is common and some families deal with these behaviors for decades prior to seeking medical attention.

Prior to the onset, and early in the course of PD, DEB progresses in frequency and intensity. Then late in the disease state a moderation of RBD occurs, likely secondary to diffuse motor circuit impairment [6].

Surveys have revealed that some DEB is nearly universal with 98 % of college-aged students reporting at least one episode of DEB [7]. The vast majority of these cases, however, are transient and nondistressing. Various reports have suggested that the prevalence of RBD is approximately 0.5 % in the general population [5], with higher prevalence among patients with neurodegenerative disease, other sleep disorders, or on antidepressant medications [5, 8]. Thus, there are approximately 35 million patients worldwide; however, the clinical symptoms are frequently dismissed and thus vast majority of cases remain undiagnosed for a long time.

As noted above, RBD is often a heralding manifestation of PD and is common among other alpha-synuclein disorders. According to several studies, approximately one-third to one-half of patients with PD have RBD [6, 9, 10]. Among similar pathologies the frequency is even higher, with 50–80 % of patients with DLB and 80–95 % of patients with MSA [6, 11].

Similar to PD, RBD is associated with various environmental and behavioral risk factors. In particular, RBD patients are more likely to smoke, have a history of traumatic brain injury, farming, pesticide exposure, and fewer years of education [12].

The majority of reported cases are males; however, female RBD is likely underreported. Women present with less injurious dream enactment and thus are less likely to receive medical attention. Further, due to the gender difference in life expectancy, elderly women are less likely to have bed partners than elderly men, and thus less likely to have witnessed parasomnia behaviors [13, 14].

Patients with RBD demonstrate clinical and subclinical phenomena suggestive of an impending alpha-synuclein CNS pathology. When fully developed, these disorders manifest as either PD, MSA, DLB or rarely pure autonomic failure.

Motor testing in RBD demonstrates slight, often imperceptible parkinsonian abnormalities. In particular, subtle changes are noted on the Purdue Peg Board, alternate tap test, the Unified Parkinson’s Disease Rating Scale (UPDRS), and timed evaluation of standing and walking [15]. Further, in a survey of normal elderly individuals, the presence of RBD symptoms was associated with at least mild parkinsonian exam findings [6].

Patients with RBD also have subtle cognitive dysfunction. Studies have demonstrated impairments in visuospatial skills as well as in color and facial expression identification [15, 16]. Other investigations have revealed deficits in attention and executive function [6]. Prospectively, the presence of RBD symptoms confers a greater than twofold risk of developing mild cognitive impairment (MCI) over 4 years [17]. Conversely, among patients with MCI or dementia the presence of RBD helps distinguish DLB from Alzheimer’s disease [6, 18].

As in PD, hyposmia/anosmia is frequently noted in RBD. Over half of RBD patients have impairments in smell identification, compared to 10–15 % in age-matched controls [15, 19]. The most common deficit is an inability to identify paint thinner [19]. RBD and hyposmia in combination with impaired color identification place the patient at very high risk of impending PD [16].

In RBD, autonomic dysfunction is consistent with an evolving neurodegenerative disorder. Comorbid enteric neuron pathology manifests as constipation [15] and similar to hyposmia, when combined with impaired color vision predicts progression to PD [20]. Heart rate responses to both orthostasis and arousal are blunted compared to controls and intermediate compared to PD [21]. Cardiac scintigraphy has been used to predict a parkinsonian syndrome. Among RBD patients, reduced uptake of (123) I-metaiodobenzylguanidine, indicating sympathetic denervation, has been demonstrated in PD and DLB but not in MSA [6, 22].

Prior to the hallmark destruction of dopamine-producing neurons in the substantia nigra (SN), early alpha-synuclein degeneration occurs in the brainstem nuclei that control REM sleep. Under physiological circumstances the suppression of motor activity during REM is the cumulative result of multiple pathways that ultimately terminate on spinal motor neurons, most notably via the magnocellular reticular formation in the medulla. Multiple areas of the brainstem may influence muscle tone including pontine REM-on (precoeruleus and sublateral dorsal) and REM-off (ventral lateral portion of the periaqueductal gray matter and lateral pontine tegmentum) nuclei [6]. Decreased neuronal fiber integrity is seen in these REM-regulating regions among patients with RBD [29].

By the time PD motor abnormalities develop, the majority of dopaminergic cells in the substantial nigra (SN) are dysfunctional. However, in RBD patients who have not yet manifested parkinsonism, neuroimaging reveals a coincident and progressive reduction in dopamine transporters and innervation [30, 31]. Further, transcranial ultrasound hyperechogenicity of substantial nigra in RBD resembles abnormalities seen in PD [32].

Cholinergic function is impaired in RBD and correlates with cognitive decline. Among PD subjects with RBD compared to PD subjects without RBD positron emission tomography reveals cholinergic denervation [33]. These findings are similar to those seen in transcranial magnetic stimulation studies that demonstrate reduced short latency inhibition, indicating impaired cholinergic activity, in RBD. These cholinergic deficits are linked with deficiencies in episodic verbal memory, executive function, and visuospatial cognitive domains [27].

Cortical abnormalities, similar to those seen in PD and related disorders, are noted in patients with RBD. Voxel-based morphology studies demonstrate gray matter reductions that correlate with decreased regional cerebral blood flow (rCBF) in the parieto-occipital and hippocampal regions [34, 35]. Also, an increase in hippocampal rCBF is noted in RBD patients with MCI and predicts those who will ultimately progress to either PD or DLB [36].

RBD is not associated only with alpha-synuclein neurodegenerative disorders. Other etiologies include other forms of neurodegeneration, side effects of medications, structural CNS lesions, and narcolepsy linked to the orexin dysfunction. RBD has been reported in tauopathy-related parkinsonian syndromes (progressive supranuclear palsy, Guadeloupean parkinsonism, corticobasal degeneration), TDP-43opathies (frontotemporal dementia, amyotrophic lateral sclerosis), trinucleotide repeat disorders (SCA-3, Huntington’s disease), and rarely amyloidopathies (Alzheimer’s disease) [6]. However, these disorders are not typically preceded by RBD, but instead RBD develops after the onset of other neurological deficits. Medications such as tricyclic antidepressants and serotonin-specific reuptake inhibitors can precipitate or exacerbate RBD [6, 37]. It is uncertain whether these medications cause a de-novo RBD or, unmask latent RBD. Occasionally, various vascular, demyelinating, and traumatic etiologies are linked to development of RBD [38]. In these cases, cranial imaging typically demonstrates pontine tegmentum pathology. Finally, impaired orexin function can precipitate DEB, with up to 50 % of narcolepsy patients having RBD symptoms. This association is strongest among narcolepsy patients with cataplexy [39].