Rapid eye movement sleep behavior disorder

Rapid eye movement sleep behavior disorder, or REM sleep behavior disorder (RBD), is a sleep disorder in which people act out their dreams. It involves abnormal behavior during the sleep phase with rapid eye movement (REM) sleep. The major feature of RBD is loss of muscle atonia (i.e., the loss of paralysis) during otherwise intact REM sleep (during which paralysis is not only normal but necessary). The loss of motor inhibition leads to sleep behaviors ranging from simple limb twitches to more complex integrated movements that can be violent or result in injury to either the individual or their bedmates.

RBD is a very strong predictor of progression to a synucleinopathy (usually Parkinson's disease or dementia with Lewy bodies). Idiopathic RBD is the term used when RBD is not associated with another ongoing neurological condition.

Dream enactment behaviour is a core feature of RBD but is not an exclusive marker of the disorder; therefore, a history of recurrent dream enacting behaviour is only enough to receive a diagnosis of clinically probable RBD and the diagnosis of definite RBD is only given when there is polysomnography confirmation of complex motor behaviour during REM sleep. When RBD occurs in the absence of any known aetiology of the disorder it is referred to as idiopathic, however when RBD arises in relation to another neurological disorder or neurodegenerative disease, it is referred to as secondary or symptomatic RBD.

Symptomatic RBD can also be associated with narcolepsy, Guillain–Barré syndrome, limbic encephalitis, and Morvan's syndrome.

Other symptoms found in patients with RBD are reduced motor abilities, posture and gait changes, mild cognitive impairment, alterations in the sense of smell, impairments in color vision, autonomic dysfunction (orthostatic hypotension, constipation, urinary problems and sexual dysfunction), and depression. including those in the pontomedullary brainstem.

Neuropathology of RBD in PD

There are a number of proposed explanations put forth by researchers to try and explain the cognitively impaired phenotype of PD that is linked to RBD. The first is that RBD affects sleep quality/content, which in turn could lead to cognitive dysfunction through various neuronal mechanisms. However, there is not much research support for this idea and there is a lack of association between different sleep disorders, such as insomnia, and cognitive decline in PD.

Another proposed explanation for the increased cognitive decline seen in PDRBD, is due to alterations in neurotransmitter systems. In particular, greater cholinergic denervation in PD patients with RBD compared to those without. This difference is seen particularly in brain structures like the basal forebrain, an area implicated in both cognition and the regulation of REM sleep and muscle tone through interactions with brainstem nuclei. The increased cholinergic denervation is proposed to appear in the third phase of Braak staging, in which Lewy body pathology in a PD brain appears in the basal forebrain and is thought to cause the reduction in cholinergic neurotransmitters. Thus, cholinergic reduction could play a key role in the pathogenesis of RBD in PD and the cognitive impairment found in these patients, making this a potential marker for a specific cognitive subset of PD. This hypothesis is supported by the amelioration of RBD symptoms through the use of acetylcholinesterase inhibitors, drugs which lead to an increase in cholinergic neurotransmitters in the brain. However, there are a lot of inconsistent results within the literature surrounding differences in grey matter volume, and so alterations in brain matter volume are seen as a less reliable neurological marker.

Diagnosis

There are two ways to diagnose RBD: by documenting a history of complex, dream-enactment sleep behaviors, or by polysomnography recording of these behaviors along with REM sleep atonia loss.

RBD may be established from clinical interview as well as several validated questionnaires, when sleep studies cannot be performed.</blockquote>

Diagnostic criteria for RBD from the International Classification of Sleep Disorders (ICSD-3) are:

Repetition of vocalizations and/or complex motor behaviors during sleep
Polysomnography (PSG) show that these behaviors occur during REM sleep
If documentation of these behaviors by PSG is not possible, they must at least be assumed to take place during REM sleep based on records of dream enactment
REM sleep without atonia (RWA) can be seen in polysomnographic recordings
Episodes cannot be explained by another mental disorder, sleep disorder, substance abuse or medication

Differential

Other conditions are similar to RBD in that individuals exhibit excessive sleep movement and potentially violent behavior. Such disorders include non-REM parasomnias (sleepwalking, sleep terrors), periodic limb movement disorder, severe obstructive sleep apnea, and dissociative disorders.

When observing both cross-sectional and longitudinal data regarding RBD and PD, deficits in global cognitive functioning, attention/working memory, language, executive functions, and visuospatial abilities can be seen in patients with RBD and PD (PDRBD); especially in comparison to PD patients without RBD (PD non-RBD). PDRBD show significantly greater annual rates of decline on established cognitive tests such as the MoCA test,

The difference in overall cognitive decline between PDRBD and PD non-RBD is replicated in studies conducted in many different cultures and remains strong regardless of whether participants are drug naïve or taking some form of dopaminergic treatment to aid with their PD. However, the existence of a unique and specific cognitively impaired profile among PD patients with RBD is still deemed controversial. This is mainly due to methodological limitations among the literature; such as the absence of polysomnography in the diagnosis of RBD, the use of tests with poor sensitivity when measuring cognition and testing for cognitive deficits, as well as small sample sizes. but melatonin offers a safer alternative, because clonazepam can produce undesirable side effects.

Medications that may worsen RBD and should be stopped if possible are tramadol, mirtazapine, antidepressants, and beta blockers.

Patients are advised to maintain a normal sleep schedule, avoid sleep deprivation, and keep track of any sleepiness they may have. Treatment includes regulating neurologic symptoms and treating any other sleep disorders that might interfere with sleep. Sleep deprivation, alcohol, certain medications, and other sleep disorders can all increase RBD and should be avoided if possible.

Prognosis

Patients with RBD are at risk for sleep-related injury.

Epidemiology

Synucleinopathies are associated with RBD. RBD prevalence as of 2017 is estimated to be 0.5–2% overall, and 5–13% of those aged 60 to 99. On autopsy, up to 98% of individuals with polysomnography-confirmed RBD are found to have a synucleinopathy. The diagnosis and symptom onset of RBD typically precedes the onset of motor or cognitive symptoms of PD by a number of years, typically ranging anywhere from 2 to 15 years prior. Hence, this link could provide an important window of opportunity in the implementation of therapies and treatments, that could prevent or slow the onset of PD.

History

In the 1960s and 1970s, Michel Jouvet described brain lesions in cats that led to loss of atonia in REM sleep. Carlos Schenck and Mark Mahowald and their team in Minnesota first described RBD in 1986.

In animals

RBD has also been diagnosed in animals, specifically dogs.