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Top 10 Articles

Top Article: Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder

December 1, 2012

Abstract

Objective: Idiopathic REM sleep behavior disorder (RBD) is a potential preclinical marker for the development of neurodegenerative diseases, particularly Parkinson disease (PD) and Lewy body dementia. However, the long-term risk of developing neurodegeneration in patients with idiopathic RBD has not been established. Obtaining an accurate picture of this risk is essential for counseling patients and for development of potential neuroprotective therapies.
Methods: We conducted a follow-up study of all patients seen at the sleep disorders laboratory at the Hôpital du Sacré Coeur with a diagnosis of idiopathic RBD. Diagnoses of parkinsonism and dementia were defined according to standard criteria. Survival curves were constructed to estimate the 5-, 10-, and 12-year risk of developing neurodegenerative disease.
Results: Of 113 patients, 93 (82%) met inclusion criteria. The mean age of participants was 65.4 years and 75 patients (80.4%) were men. Over the follow-up period, 26/93 patients developed a neurodegenerative disorder. A total of 14 patients developed PD, 7 developed Lewy body dementia, 4 developed dementia that met clinical criteria for AD, and 1 developed multiple system atrophy. The estimated 5-year risk of neurodegenerative disease was 17.7%, the 10-year risk was 40.6%, and the 12-year risk was 52.4%.
Conclusions: Although we have found a slightly lower risk than other reports, the risk of developing neurodegenerative disease in idiopathic REM sleep behavior disorder is substantial, with the majority of patients developing Parkinson disease and Lewy body dementia.

Postuma RB, Gagnon JF, Vendette M, Fantini ML, Massicotte-Marquez J, Montpaisir J. Neurology 2009;72, April:1296–1300

Comment by Samson Khachatryan

Rapid eye movement sleep behaviour disorder (RBD) is a parasomnia originating from rapid eye movement (REM) sleep with a hallmark sign of atonia loss in REM-sleep and motor enactment of dream content in the form of fighting, punching, kicking, talking, crying, escaping, avoiding animals, etc. It exists in two clinical forms: idiopathic and secondary. Most of the cases of secondary RBD are found in parkinsonian disorders. Moreover, recent evidence places RBD on a new level of importance, as it has been suggested to be a premotor sign and a predictor of neurodegenerative disease, the strongest association being for synucleinopathies (Parkinson disease, Lewy body dementia, and multiple system atrophy). A few studies exist which demonstrate obvious high transformation rates from idiopathic RBD to any type of parkinsonian disorder. First, Schenk et al. (1996), then Iranzo et al. (2006), demonstrated their case series with differing but substantial rates of transformation after a median of 5 years of follow-up (38% and 45% correspondingly). This raised awareness of RBD, supported by the idea of developing any possible neuroprotective agents in future able to stop the progression. Identification of idiopathic RBD could help for initiating this treatment at the earliest stages of neurodegenerative disease.
In this study, Postuma et al. were able to show that an essential proportion of their patients initially diagnosed as idiopathic RBD finally developed neurodegenerative disease being predominantly parkinsonian disorders. Of the general database, a total of 113 patients with idiopathic RBD who attended sleep disorders laboratory from 1989 to 2006 were considered for the study. Of these patients, 93 (82.3%) met inclusion criteria. The authors performed a profound assessment of most of the patients utilizing standardized criteria for clinical and laboratory diagnosis of RBD and direct patient visits with full clinical assessment (n=78). A small number of patients were also enrolled who were not able to attend full in-person evaluation with follow-ups and passed thorough telephone assessment conducted by a neurologist (n=15). Diagnoses of parkinsonian disorders were clinical and not confirmed by autopsy. The authors found a slightly lower proportion of idiopathic RBD converting to parkinsonian disorder than previous reports did. Still a significant number of patients (n=26, 27.9%) in this study developed neurodegenerative disease over a mean of 5.2 years follow-up. Of these patients, 15 developed parkinsonism (Parkinson disease – 14, Multiple system atrophy – 1), and 11 developed dementia. Interestingly, in the latter group mostly representing probable Lewy body dementia (LBD) cases (7), 4 cases of clinical Alzheimer disease were diagnosed. However, according to the authors, later evaluations raised a possibility these cases could also meet the criteria for LBD. Using survival curves, Postuma et al. estimated a 5-year risk of developing neurodegenerative disease at 17.7%. The estimated 10-year risk was 40.6% and the 12-year risk was 52.4%. Importantly, these risks remained constant over the follow-up period. The authors compared the group which met strict inclusion criteria with data from all included patients and found similar results for estimated risks. This study has an important advantage of using a new approach in assessing the risk of developing parkinsonian disorder using a life table analysis. The latter method utilizes censored data which helps to estimate risk at later time points (10 or 12 years).
Of note, this was the largest case series of idiopathic RBD follow-up, also utilizing a method of survival curve construction to better assess the risk of neurodegenerative disease, definitely increasing the value of this study. The results of this and other similar studies help neurologists and other involved specialists to better understand the role of idiopathic RBD in development of synucleinopathies. It is also important to use this knowledge for adequate counselling of the patients at risk. Finally, it is desirable, that every neurologist becomes familiar with RBD and is able to identify this important premotor sign of neurodegenerative disease as soon as possible.

Samson Khachatryan is a member of EFNS Scientist panel on sleep disorders, and working at the Department of Neurology, Yerevan State Medical University and director at Somnus Sleep and Movement Disorders Clinic, Yerevan, Armenia

 

Top Article: Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder was last modified: November 28th, 2012 by Editor
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All content from January 2012 - June 2013 was published by EFNS; content from July 2013 - June 2014 by EFNS and ENS.

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