It was a ferocious fight–all tangled fur, flailing limbs, and the glide of wet, snarling teeth–as he hooked his arm over the animal’s shoulders and got it into a chokehold. For a few sweet, disbelief-filled seconds, it seemed as though the man had saved himself. Then, he heard the scream: “Ah! I can’t breathe–stop it–let me go!”

What had seemed, moments ago, like a vicious fight for his life soon revealed itself to be a violent episode of REM Sleep Behavior Disorder (RBD). The man opened his eyes to his red-faced wife, from whom he learned that he had not been outdoors, or near a bear. The whole time, he had been lying in the soft, dark comfort of his bedroom. His nemesis had, in truth, been his own wife. This man’s experience reflects that of roughly one percent of the population: people living with RBD, whose dreams are just as real as their reality [1].

Counting Electric Sheep

To better understand REM Sleep Behavior Disorder, we will begin by examining the function of REM sleep under “normal” circumstances. An average person’s night of sleep consists of approximately four to five cycles of five main stages: wake, three stages of non-REM sleep (abbrev. NREM; divided into N1, N2, and N3), and REM [Figure 1,2].

REM stands for “rapid eye movements” and is the key feature of this stage of sleep [3]. The other stages of sleep are, intuitively, known as NREM stages because rapid eye movements are not observed in them. Some sleep scientists split NREM into 4 stages, while others consolidate stages 3 and 4 into a single ‘N3’. A complete cycle of sleep takes approximately 90 to 110 minutes. As the night progresses, time spent in deep NREM sleep decreases in duration while time spent in REM sleep increases. This trend may be why most episodes of RBD occur toward the end of the sleep period, typically after 3:00 AM [1].

REM sleep is also notable for being the stage of sleep where we dream [2]. For many people, dreaming is mostly limited to the inner boundaries of the mind. Almost all skeletal muscles are atonic, or limp and paralyzed, during REM sleep [1]. This prevents us from physically acting out the contents of our dreams. From the outside, we can observe that a person is in REM sleep through the use of tools like electroencephalography (EEG), which measures electrical activity in the brain; electrooculography (EOG), which measures activity in the eyes; and electromyography (EMG), which measures activity in body muscles, usually the chin and calves for sleep studies. These tools are often used in conjunction to study sleep, in a testing bundle known as polysomnography (PSG) [4,5].

PSG helps sleep researchers observe objective differences between the stages of NREM and REM sleep [5]. The data collected through PSG can be depicted on a hypnogram, where the stages of wake and sleep can be observed as a function of time [Figure 1]. On a hypnogram, we can observe that a person’s progression through the different levels of sleep is akin to traversing a set of narrow peaks and valleys [Figure 1]. The wakeful state is represented by the highest peak, followed by a descent into sleep. First, consciousness skis downhill on a steep slide to N1, followed by progression into N2, and, finally, the deepest stage: N3/N4 [2].

After the deepest stage of sleep comes a climb back to N2, followed by a brief period of REM sleep, during which brain activity most resembles wakefulness. In REM sleep, the EEG recording looks similar to both that of N1, the ‘lightest’ stage of sleep, and wakefulness [Figure 2,5]. Key attributes of REM sleep include high EOG activity, courtesy of the stage’s namesake, while EMG recordings during REM sleep tend to display the lowest activity, as a result of the muscle atonia keeping the body still as the mind embarks upon dreams [3].

The A-B-C’s of R-B-D

For some people, the everyday processes of falling into sleep, staying asleep, or waking up from their slumber can become compromised. Interruptions in any of these events may introduce a “parasomnia.” This broad term, covering myriad conditions, has Greco-Latin roots; the prefix para- sprouts from Greek and means ‘alongside,’ while the Latin noun Somnus means ‘sleep’ [6].

Some well-known parasomnias include sleepwalking or sleep terrors, which mostly occur in younger individuals and often involve the NREM stages of sleep and waking [6]. RBD, on the other hand, primarily implicates REM sleep and is most common in older adults. Where the muscles of the body should be atonic, except for rapid movements of the eye muscles, we instead see patients’ bodies acting on the choreography of their dreams [6].

Individuals with RBD may fail to notice their symptoms on their own because they are asleep. Frequently, the person experiencing RBD is clued into their condition only when a bed partner is awakened by and grows concerned over disturbing dream enactments [7]. A person experiencing RBD may exhibit a range of nighttime behaviors, from simple to complex, during REM sleep. Some common examples include: “talking, laughing, shouting, gesturing, grabbing, flailing arms, punching, kicking, and sitting up or leaping from bed” [8].

The American Academy of Neurology published an interview conducted with a patient experiencing RBD and his bed partner, in which the bed partner describes observing the patient running vigorously under the covers and throwing himself out of bed, past furniture and electronics [7]. He remains asleep throughout all of these actions until he hurts or shocks himself after landing on the floor. This dynamic brings insight into the nosology, or classification, of RBD as a disorder: it may be an even more distressing condition to the bed partner than to the patient [9]. The patient is sound asleep when their disease manifests and may remember unpleasant dreams and notice unusual injuries upon awakening. The bed partner, on the other hand, may be awakened by or lose sleep over multiple nights, as they anticipate the patient’s injurious behaviors [7].

Clinicians make the diagnosis of RBD through clinical interview, taking an in-depth history of the patient’s sleep disturbances and dream enactments, followed by video polysomnography (VPSG) to confirm [Figure 3,4]. VPSG entails a video-EEG–which couples the EEG data with a videotape recording of the patient’s sleep behaviors in the clinic–and cardiorespiratory measurements, EMG, and EOG [10]. Once a VPSG has been conducted, it is scored and charted, allowing the clinician to determine abnormalities from video evidence, physiological recordings, and the patient’s hypnogram [Figure 1, Figure 2]. PSG is a standard test used in the diagnosis of most sleep disorders, not only RBD [10].

RBD: TBD

To date, the treatment recommendations for RBD focus on creating a safer sleeping environment for the patient and making pharmacological adjustments that may reduce dangerous dream enactments [8]. Patients are counseled to remove sharp or fragile furniture and objects from the sleeping environment. Additional protections that may prevent injuries include padded bed rails, or a sleeping bag [8].

The preferred pharmacotherapy for RBD patients is melatonin because it is an endogenous (originating from within the body) hormone [1,8,11]. Melatonin production in the body peaks in darkness, at night, and promotes the drive to sleep [12]. This hormone has been observed to resynchronize the body’s circadian rhythms and improve RBD symptoms and REM sleep atonia through an unknown mechanism [11].

In more extreme cases of RBD, low-dose clonazepam (traditionally used to treat seizures), is prescribed to ease symptoms and decrease the rate of injury [1,8]. However, while clonazepam may appear more effective than melatonin in controlling RBD, the cost of its negative side effects (e.g., sedation, confusion, memory issues) may outweigh its benefits, especially in cognitively impaired populations [1].

While there are multiple theories attempting to explain clonazepam’s mechanism of action with regard to managing RBD, it is also yet unknown [8]. Furthermore, a 2013 retrospective study comparing melatonin and clonazepam treatment for RBD found the two pharmacological solutions comparably effective [13]. This study provides additional support for the prescription of melatonin over clonazepam to treat RBD symptoms, when possible.

The added risk that prescribing clonazepam to treat RBD brings for cognitively impaired patients is especially important to beware of in the context of the link between RBD and the development of alpha-synuclein neurodegenerative disorders (i.e, Parkinson’s disease, dementia with Lewy body, or multiple system atrophy) [14]. Between 35% and 91.9% of patients initially diagnosed with idiopathic (without other known causes) RBD later develops a neurodegenerative disease [14,15]. These patients are usually in their sixth or seventh decade of life, male, and the overall conversion rate of RBD to neurodegenerative disease per year is 6.25%, with the median time to convert being 8 years [15].

Individuals may also develop RBD for reasons unlinked to neurodegenerative disease [14]. In RBD patients with less than fifty years of age, factors such as narcolepsy, autoimmune disorders, brain lesions, or antidepressant use have been observed to indicate an increased risk for RBD [14,16].

In spite of the large number of unknowns at play in the diagnosis and management of RBD, numerous therapies and preventative measures are in development [17]. These include the exploration of additional drug therapies, as well as non-pharmacological therapies, such as custom bed alarms and protective exercise regimens [17]. The existence of RBD as a possible prodromal, or pre-disease state, for neurodegenerative diseases also represents a promising opportunity to develop and enact neuroprotective therapies that may serve to prevent alpha-synucleinopathies [14]. In this light, RBD bodes not only nightmares but brilliant dreams for the future of sleep medicine and neurology.

References

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