Neurophysiological basis of rapid eye movement sleep behavior disorder:Informing future drug development

Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by a history of recurrent nocturnal dream enactment behavior and loss of skeletal muscle atonia and increased phasic muscle activity during REM sleep: REM sleep without atonia. RBD and associated comorbidities have recently been identified as one of the most specific and potentially sensitive risk factors for later development of any of the alpha-synucleinopathies: Parkinson’s disease, dementia with Lewy bodies, and other atypical parkinsonian syndromes. Several other sleep-related abnormalities have recently been identified in patients with RBD/Parkinson’s disease who experience abnormalities in sleep electroencephalographic frequencies, sleep–wake transitions, wake and sleep stability, occurrence and morphology of sleep spindles, and electrooculography measures. These findings suggest a gradual involvement of the brainstem and other structures, which is in line with the gradual involvement known in these disorders. We propose that these findings may help identify biomarkers of individuals at high risk of subsequent conversion to parkinsonism

Sleep spindle alterations in patients with Parkinson's disease

The aim of this study was to identify changes of sleep spindles (SS) in the EEG of patients with Parkinson's disease (PD). Five sleep experts manually identified SS at a central scalp location (C3-A2) in 15 PD and 15 age- and sex-matched control subjects. Each SS was given a confidence score, and by using a group consensus rule, 901 SS were identified and characterized by their (1) duration, (2) oscillation frequency, (3) maximum peak-to-peak amplitude, (4) percent-to-peak amplitude, and (5) density. Between-group comparisons were made for all SS characteristics computed, and significant changes for PD patients vs. control subjects were found for duration, oscillation frequency, maximum peak-to-peak amplitude and density. Specifically, SS density was lower, duration was longer, oscillation frequency slower and maximum peak-to-peak amplitude higher in patients vs. controls. We also computed inter-expert reliability in SS scoring and found a significantly lower reliability in scoring definite SS in patients when compared to controls. How neurodegeneration in PD could influence SS characteristics is discussed. We also note that the SS morphological changes observed here may affect automatic detection of SS in patients with PD or other neurodegenerative disorders (NDDs)

Increased Motor Activity During REM Sleep Is Linked with Dopamine Function in Idiopathic REM Sleep Behavior Disorder and Parkinson Disease

STUDY OBJECTIVES: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia characterized by impaired motor inhibition during REM sleep, and dream-enacting behavior. RBD is especially associated with α-synucleinopathies, such as Parkinson disease (PD). Follow-up studies have shown that patients with idiopathic RBD (iRBD) have an increased risk of developing an α-synucleinopathy in later life. Although abundant studies have shown that degeneration of the nigrostriatal dopaminergic system is associated with daytime motor function in Parkinson disease, only few studies have investigated the relation between this system and electromyographic (EMG) activity during sleep. The objective of this study was to investigate the relationship between the nigrostriatal dopamine system and muscle activity during sleep in iRBD and PD. METHODS: 10 iRBD patients, 10 PD patients with PD, 10 PD patients without RBD, and 10 healthy controls were included and assessed with (123)I-N-omega-fluoropropyl-2-beta-carboxymethoxy-3beta-(4-iodophenyl) nortropane ((123)I-FP-CIT) Single-photon emission computed tomography (SPECT) scanning ((123)I-FP-CIT SPECT), neurological examination, and polysomnography. RESULTS: iRBD patients and PD patients with RBD had increased EMG-activity compared to healthy controls. (123)I-FP-CIT uptake in the putamen-region was highest in controls, followed by iRBD patients, and lowest in PD patients. In iRBD patients, EMG-activity in the mentalis muscle was correlated to (123)I-FP-CIT uptake in the putamen. In PD patients, EMG-activity was correlated to anti-Parkinson medication. CONCLUSIONS: Our results support the hypothesis that increased EMG-activity during REM sleep is at least partly linked to the nigrostriatal dopamine system in iRBD, and with dopamine function in PD. CITATION: Zoetmulder M, Nikolic M, Biernat H, Korbo L, Friberg L, Jennum P. Increased motor activity during rem sleep is linked with dopamine function in idiopathic REM sleep behavior disorder and Parkinson disease. J Clin Sleep Med 2016;12(6):895–903