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

Abstract

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-omegafluoropropyl-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. I NTRO DUCTI O NREM sleep behavior disorder (RBD) is a parasomnia characterized by REM sleep without atonia , dream enactment behavior, and vivid (and/or) violent dreams. Longitudinal studies have shown that patients with idiopathic RBD (iRBD) have an increased risk for developing an α-synucleinopathy, such as Parkinson disease (PD).1,2 The high proportion of iRBD patients developing PD may indicate a link between nigrostriatal degeneration and increased night-time motor activity. It is increasingly recognized that the dopaminergic system is associated with sleep-wake disturbances.3,4 Previous studies have shown that basal ganglia structures, such as the substantia nigra pars reticulata and the internal segment of the globus pallidus, have caudal connections to regions that modulate REM sleep atonia. 5 Imaging studies in iRBD patients have shown microstructural changes in substantia nigra, 6 reduced volume of the putamen, 7 as well as reduced density of the striatal dopamine transporter, which decreases in the course of disease progression. 8 In addition monkeys treated sub-chronic with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), a neurotoxin which specifically targets dopaminergic neurons of the substantia nigra...

Physical activity measured with wrist and ankle accelerometers: Age, gender, and BMI effects

“…The difference in intra-subject PA variability between the wrist and ankle as a function of time of day suggests differential diurnal control of movement in upper and lower extremities. Indeed, differential involvement of the lower and upper limbs has been reported in movement disorders at nighttime [ 58 , 59 ]. Future studies are needed to evaluate the relationship between brain function and differences of PA variability between wrist and ankle at daytime and nighttime.…”

Rapid eye movement sleep without atonia constitutes increased risk for neurodegenerative disorders

“…Current understanding of RBD—in regard to data coming from autopsy studies—revealed that degeneration of nuclei in pontine tegmentum and medial medulla oblongata are responsible for the loss of muscular atonia during REM sleep with concurrent dream enactment . In another study, loss of atonia in REM sleep was at least partly linked to nigrostriatal dopaminergic system in iRBD . It has been suggested that tonic or phasic EMG activity in REM sleep might reflect pathologies in separate brainstem structures .…”

Neuroimaging of Sleep Disturbances in Movement Disorders

“…A [ 123 I]FP-CIT-SPECT study by Eisensehr observed that muscle activity during REM sleep lasting persistently longer than 0.5 s was independently associated with reduced striatal [ 123 I]IPT uptake in iRBD patients ( 39 ). Although these results were not reproduced by Kim and colleagues, who found that electromyography (EMG) activities during REM sleep were not associated with striatal DAT density ( 36 ), they were partially replicated by Zoetmulder and colleagues who illustrated that EMG-activity in the mentalis muscle correlated with putaminal [ 123 I]FP-CIT uptake in iRBD patients, ( 42 ). Although these findings suggest that amplified muscle activity during REM sleep is associated to nigrostriatal dopaminergic system in RBD and dopaminergic function in PD, it may not be essential for the development of RBD, thus not directly associated with the severity of RBD symptomology in PD.…”