A data-driven system to identify REM sleep behavior disorder and to predict its progression from the prodromal stage in Parkinson's disease

Cesari, Matteo; Christensen, J. H.; Muntean, Maria Lucia; Mollenhauer, Brit; Sixel‐Döring, Friederike; Sørensen, Helge Bjarup Dissing; Trenkwalder, Claudia; Jennum, Poul

doi:10.1016/j.sleep.2020.04.010

Cited by 36 publications

(26 citation statements)

References 49 publications

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“…First, we used the manual sleep stage scoring to compute the EM coverages. Specifically, the scoring of REM sleep might be more challenging for the PD and iRBD groups as alterations are observed in the EEG (EEG slowing (Iranzo et al, 2010), abnormal morphology or lack of sleep spindles (Christensen, Kempfner, & Zoetmulder, 2014;Christensen et al, 2015), reduced sleep stability (Christensen, Jennum, & Koch, 2016) and increased microsleep instability (Cesari et al, 2020)), the EOG (Christensen et al, 2012(Christensen et al, , 2013 and the EMG (lack of atonia). Although we limited this potential bias by including only data obtained from stable sleep stages in the analyses, future studies investigating the degree and impact of the mixed sleep stages seen in these patient groups are yet to be performed.…”

Section: Discussionmentioning

confidence: 99%

Nocturnal eye movements in patients with idiopathic rapid eye movement sleep behaviour disorder and patients with Parkinson’s disease

Christensen

Cesari

Pizza

et al. 2020

Journal of Sleep Research

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Section: Discussionmentioning

confidence: 99%

Nocturnal eye movements in patients with idiopathic rapid eye movement sleep behaviour disorder and patients with Parkinson’s disease

Christensen

Cesari

Pizza

et al. 2020

Journal of Sleep Research

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“…A recent microsleep analysis demonstrated a significant increase in micro-sleep instability in those RBE-positive PD patients who were about to convert to RBD. 21 These findings imply that RBE, RBD, and RWA appear as the result of an ongoing underlying pathological process with degeneration of nucleus subcoeruleus circuits projecting to the medullary reticular formation and spinal ventral interneurons. 2 The malfunction of gamma-aminobutyric acid (GABA)/glycine neurotransmission in the ventromedial medulla facilitates the occurrence of abnormal motor enactments.…”

Section: Discussionmentioning

confidence: 86%

“…In addition, we confirmed that RBE at baseline converts into full‐blown RBD, which is consistent with previous results, 10 because the 7 of 31 patients diagnosed with RBE at baseline all converted into full‐blown RBD after 6 years. A recent micro‐sleep analysis demonstrated a significant increase in micro‐sleep instability in those RBE‐positive PD patients who were about to convert to RBD 21 …”

Section: Discussionmentioning

confidence: 99%

Incidence and Progression of Rapid Eye Movement Behavior Disorder in Early Parkinson's Disease

Zimansky

Muntean

Leha

et al. 2021

Movement Disord Clin Pract

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BackgroundBackground: Rapid eye movement (REM) sleep behavior disorder (RBD) is associated with neurodegenerative diseases; however, few longitudinal studies assess the individual evolution of RBD and REM sleep without atonia (RWA) in Parkinson's disease (PD). Objectives Objectives: We aimed to evaluate RBD and RWA changes over time as well as potentially influential factors. Methods Methods: RBD and RWA were analyzed using video-supported polysomnography (vPSG) in initially de novo PD patients at baseline and every 2 years for a total of 6 years. The influence of time, age, sex, levodopa equivalent daily dose (LEDD), unified Parkinson's disease rating scale (UPDRS) sum scores, benzodiazepine intake, Mini-Mental State Examination (MMSE) total scores, and dyskinesia on RWA were investigated using mixed-effect models to account for intra-individual correlations. Results Results: After 6 years, vPSG data were available from 98 of the initial 159 de novo PD patients. RBD prevalence increased from 25% at baseline to 52%. Of the 31 PD patients with RBD and valid vPSGs at all time-points, RWA increased from an average of 19% at baseline to 41% at 6-year follow-up modeled to grow by 29.7% every 2 years (P < 0.001). Time was an independent factor (P < 0.001) for RWA increase. Age was an independent factor influencing RWA increase (P = 0.04). Sex, LEDD, UPDRS sum scores, benzodiazepines, MMSE total scores, and dyskinesia did not have any significant influence. Conclusions Conclusions: RBD and RWA increased significantly over time in PD; time and age were independent factors in a prospective cohort. RBD and RWA can be considered PD progression markers.Rapid eye movement (REM) sleep behavior disorder (RBD), a parasomnia characterized by dream-enacting motor behaviors and/or vocalizations, 1,2 is a precursor to neurodegenerative diseases associated with the misprocessing of α-synuclein. 3,4 A recent meta-analysis calculated an annual conversion rate of 6.3% of patients with isolated RBD (iRBD) into any neurodegenerative disease. 5 Data from functional imaging studies 6 highlighted the role of RBD as a premotor manifestation of Parkinson's disease (PD) and as a diagnostic marker for α-synuclein aggregation disorders. A recent study using the REM sleep behavior screening questionnaire tried to identify "probable RBD" and an association was found between motor and cognitive decline in probable RBD patients. 7 In manifest PD, a recent meta-analysis (n = 2462) calculated an overall mean prevalence of RBD of 23.6% in newly diagnosed PD, with a wide range (4.3%-69.4%) most likely because of the lack of polysomnographic validation in all but 1 of the 8 studies. 8 This 1 study comprised the baseline report of our de novo Parkinson (DeNoPa) sleep cohort and identified polysomnographically validated RBD in 25% of newly diagnosed, drug-naïve PD patients. 9 RBD prevalence increased to 43% at 2-year follow-up. 10 In a large cohort of PD patients at various

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“…Cesari et al recently proposed an automated system that may be able to estimate the probability of RBD development using electroencephalographic (EEG) and electrooculographic (EOG) signaling. The most important finding of the study was that micro-sleep instability is a relevant characteristic occurring even in prodromal stages of RBD and therefore it may be considered a possible biomarker to identify RBD in PD patients (18).…”

Section: Biomarkers and Clinical Correlationsmentioning

confidence: 97%

REM sleep behaviour disorder in Parkinson's disease (Review)

et al. 2021

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Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia defined by simple or complex abnormal movements occurring in REM state, instead of the physiological muscular atonia. RBD may be idiopathic, or secondary as in the case of Parkinson's disease (PD). Several studies have confirmed that idiopathic RBD may precede with several years the onset of the specific motor characteristics of PD. The high prevalence of RBD in PD (19-70%) may be explained by several common pathophysiological pathways, mainly related to the dopaminergic cell loss. RBD is also associated with several comorbidities, including cognitive impairment, hallucinations, dysautonomia, or daytime sleepiness. The gold standard investigation for the diagnosis and assessment of RBD is video polysomnography, but in clinical practice, the use of clinical scales and questionnaires is reasonable for the screening of this complex parasomnia. Management options include ensuring a safe environment for the patient and pharmacological treatment, incuding clonazepam, melatonin or certain antiparkinsonian drugs. Contents 1. Introduction 2. Pathophysiology 3. Biomarkers and clinical correlations 4. Assessment 5. Treatment 6. Conclusions

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A data-driven system to identify REM sleep behavior disorder and to predict its progression from the prodromal stage in Parkinson's disease

Cited by 36 publications

References 49 publications

Nocturnal eye movements in patients with idiopathic rapid eye movement sleep behaviour disorder and patients with Parkinson’s disease

Nocturnal eye movements in patients with idiopathic rapid eye movement sleep behaviour disorder and patients with Parkinson’s disease

Incidence and Progression of Rapid Eye Movement Behavior Disorder in Early Parkinson's Disease

REM sleep behaviour disorder in Parkinson's disease (Review)

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