Update on REM sleep behaviour disorder

This is a great review of the latest understanding about REM sleep behaviour disorder (RBD), which has been closely associated with risk for Parkinson's disease. The condition was first described in cats with damage to the midbrain, the area in the brainstem above the substantia nigra, where the cells damaged in Parkinson's disease reside. The hallmark of the condition is loss of normal muscle paralysis during REM sleep, the state in which most dreams occur, so that dreams are acted out.

In itself the condition can be more or less benign, with some patients hardly noticing any issues and others harming themselves badly at night. But importantly, it is now clearly linked with Parkinson's disease - many patients with Parkinson's go on to get the disorder and patients with RBD are at higher risk of going on to get Parkinson's. Increasing evidence shows a common underlying disease process, with build up of the protein alpha-synuclein. As a risk factor, unlike age or smell loss, it is highly specific for Parkinson's, or the related condition lewy body dementia. In patients with RBD, many have similarities to people with Parkinson's, without yet having developed movement problems - for example, there are imaging changes, autonomic changes and cognitive changes.

In the search for disease-modifying treatment, this group is likely to be very valuable - with the high rate of conversion to Parkinson's, the benefits of treatment are more likely to outweigh risks than for the general population. Continuing to characterise these patients and find the measures most sensitive to progression will ultimately enable us to recruit for clinical trials for preventative medications.

http://www.nature.com/articles/nrneurol.2017.157

Nat Rev Neurol. 2017 Nov 24. doi: 10.1038/nrneurol.2017.157. [Epub ahead of print]

Idiopathic REM sleep behaviour disorder and neurodegeneration - an update.

Högl B, Stefani A, Videnovic A

Abstract

So-called idiopathic rapid eye movement (REM) sleep behaviour disorder (RBD), formerly seen as a rare parasomnia, is now recognized as the prodromal stage of an α-synucleinopathy. Given the very high risk that patients with idiopathic RBD have of developing α-synucleinopathies, such as Parkinson disease (PD), PD dementia, dementia with Lewy bodies or multiple system atrophy, and the outstandingly high specificity and very long interval between the onset of idiopathic RBD and the clinical manifestations of α-synucleinopathies, the prodromal phase of this disorder represents a unique opportunity for potentially disease-modifying intervention. This Review provides an update on classic and novel biomarkers of α-synuclein-related neurodegeneration in patients with idiopathic RBD, focusing on advances in imaging and neurophysiological, cognitive, autonomic, tissue-specific and other biomarkers. We discuss the strengths, potential weaknesses and suitability of these biomarkers for identifying RBD and neurodegeneration, with an emphasis on predicting progression to overt α-synucleinopathy. The role of video polysomnography in providing quantifiable and potentially treatment-responsive biomarkers of neurodegeneration is highlighted. In light of all these advances, and the now understood role of idiopathic RBD as an early manifestation of α-synuclein disease, we call for idiopathic RBD to be reconceptualized as isolated RBD.

Key points

• Clinically isolated rapid eye movement (REM) sleep behavioural disorder (RBD) is considered to be an early stage of α-synucleinopathy that can provide a window into the future health of the brain
  
  
• Elementary, minor and major body and limb jerks on surface electromyography (REM sleep without atonia) or video polysomnography are the main hallmarks of RBD
  
  
• Accurate diagnosis of isolated RBD is critical in clinical trials and should be confirmed by polysomnography rather than implied by subjective tools such as questionnaires
  
  
• In patients with isolated RBD, conversion to α-synucleinopathy often results in Parkinson disease dementia or dementia with Lewy bodies; the highest risk of conversion has been calculated for polysomnography-confirmed isolated RBD
  
  
• The term 'prodromal RBD' should be used (in analogy to prodromal Parkinson disease) to define recognizable precursory disease states before the full diagnostic criteria for isolated RBD are met
  
  
• This prodromal stage might enable the identification of individuals at risk of neurodegeneration even before the development of isolated RBD