Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study
Iranzo A, Molinuevo JL, Santamaria J, Serradell M, Marti MJ, Valldeoriola F, et al.;
Commented by , 24 Aug 2006
Background
Rapid-eye-movement (REM) sleep behaviour disorder (RBD) is characterized by dream-enacting behaviours such as shouting and punching, usually related to scary or unpleasent dreams and lack of muscle atonia which should normally occur during REM sleep. Although RBD can be idiopathic, it has been suggested that in some cases RBD may be the initial manifestation of neurodegenerative diseases, basically those associated with synuclein pathology.
Objectives
The objective of this study was to determine the frequency and nature of neurological disorders developing in patients diagnosed to have idiopathic RBD at a single sleep centre.
Methods
Fourty-four consecutive patients with at least 2 years of clinical follow-up after a diagnosis of idiopathic RBD were retrospectively assessed using a detailed clinical history, complete neurological examination, rating scales of parkinsonism and neuropscyhological testing. There were 39 men and five women with a mean age of 74 years (age range 61-86).
Results
Twenty (45%) patients developed a neurological disorder after a mean of 11.5 (range 6-23) years from the reported onset of RBD and a mean follow-up of 5.1 years from the diagnosis of idiopathic RBD. Age at the reported onset of RBD ranged from 50 to 70 years, age at the onset of neurological disease ranged from 60 to 79.
Emerging disorders included Parkinson’s disease in nine patients, dementia with Lewy Bodies in six, multiple system atrophy with predominant cerebellar syndrome in one, and mild cognitive impairment in four in whom visuospatial dysfunction was prominent.
Patients with longer clinical follow-up were more likely to develop a neurological disease (odds ratio 1.512, p=0.010). The authors concluded that RBD often antedates the development of a neurodegenerative disorder and close follow-up of patients with idiopathic RBD could enable early detection of neurodegenerative diseases.
Professor Emre's comments
Although the identification of RBD as a parasomnia has been made decades ago, the recognition of its association with certain neurodegenerative diseases has been made rather recent. A pathological survey of patients who developed RBD in the context of a neurodegenerative dementia had revealed that the underlying pathology was a synucleinopathy in the vast majority of patients (ref. 1).
The results of this study are quite comparable, all of those patients who developed a neurodegenerative disorder during their follow-up were diagnosed to have a synuclein (or Lewy body) related disorder. This may be because brainstem nuclei are a favorite predilection site for early accumulation of Lewy bodies, as the underlying pathophysiology for RBD is thought to be dysfunction of the lower brainstem nuclei that regulate REM sleep.
Another interesting observation which has been described before (ref. 2) and has been confirmed in this study is that RBD can antedate the development of a neurodegenerative disorder by many years. This may be due to the time course of pathology in disorders such as Parkinson disease which has been suggested to initiate in certain vulnerable brainstem nuclei and then follow an ascending course (ref. 3).
The results of this study along with others are important as they demonstrate that RBD can be harbinger of a neurodegenerative disorder in a large number of patients. It may be used as a marker for early diagnosis of such disorders along with other predictive factors and may enable early intervention when disease modifying strategies become available.
References
1. Boeve BF, Silber MH, Ferman TJ, Kokmen E, Smith GE, Ivnik RJ, et al. REM sleep behavior disorder and degenerative dementia: an association likely reflecting Lewy body disease. Neurology 1998; 51 (2); 363-370
2. Schenck CH, Bundlie SR, Mahowald MW. Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology 1996; 46 (2); 388-393
3. Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiology of Aging 2003; 24 (2); 197-211