Abstract
REM sleep behaviour disorder (RBD) is a parasomnia characterized by the loss of normal skeletal muscle atonia during REM sleep with prominent motor activity accompanying dreaming. The terminology relating to RBD, and mechanisms underlying REM sleep without atonia and RBD based on data in cat and rat are presented. Neuroimaging data from the few published human cases with RBD associated with structural lesions in the brainstem are presented, in which the dorsal midbrain and pons are implicated. Pharmacological manipulations which alter RBD frequency and severity are reviewed, and the data from human neuropathological studies are presented. An anatomic framework and new schema for the pathophysiology of RBD are proposed based on recent data in rat regarding the putative flip-flop switch for REM sleep control. The structure in man analogous to the subcoeruleus region in cat and sublaterodorsal nucleus in rat is proposed as the nucleus (and its associated efferent and afferent pathways) crucial to RBD pathophysiology. The association of RBD with neurological disease ('secondary RBD') is presented, with emphasis on RBD associated with neurodegenerative disease, particularly the synucleinopathies. The hypothesized pathophysiology of RBD is presented in relation to the Braak staging system for Parkinson's disease, in which the topography and temporal sequence of synuclein pathology in the brain could explain the evolution of parkinsonism and/or dementia well after the onset of RBD. These data suggest that many patients with 'idiopathic' RBD are actually exhibiting an early clinical manifestation of an evolving neurodegenerative disorder. Such patients may be appropriate for future drug therapies that affect synuclein pathophysiology, in which the development of parkinsonism and/or dementia could be delayed or prevented. We suggest that additional clinicopathological studies be performed in patients with dementia or parkinsonism, with and without RBD, as well as in patients with idiopathic RBD, to further elucidate the pathophysiology and also characterize the clinical and pathophysiological relevance of RBD in neurodegenerative disease. Furthermore, longitudinal studies in patients with idiopathic RBD are warranted to characterize the natural history of such patients and prepare for future therapeutic trials.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2770-2788 |
| Number of pages | 19 |
| Journal | Brain |
| Volume | 130 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 2007 |
Bibliographical note
Funding Information:We are indebted to our colleagues with whom we work on the RBD/neurodegenerative disease association, namely Ann M. Schmeichel, Robert J. Ivnik, PhD, Ronald C. Petersen, PhD, MD, Keith A. Josephs, MD, Daniel A. Drubach, MD, Josephs Y. Matsumoto, MD, David S. Knopman, MD and Neill R. Graff-Radford, MBChB. We thank our staff at the Mayo Sleep Disorders Center and Mayo Alzheimer’s Disease Research Center for their evaluation and education/counselling for many of the patients and families included in this report. We particularly extend our gratitude to the patients and their families for participating in research on neurodegenerative disease, ageing, and REM sleep behaviour disorder. Supported by grants P50 AG16574, P50 NS40256, U01 AG06786, RO1 AG15866, RO1 AG23195, and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation and by a grant from the German Research Council (DFG BR 317/17-2).
Keywords
- Dementia with Lewy bodies
- Multiple system atrophy
- Parasomnia
- Parkinson's disease
- REM sleep behaviour disorder
- Synuclein
- Synucleinopathy