Combinations of Markers Provide Clues to the Underlying Neurodegenerative Disorder in REM Sleep Behavior Disorder

Introduction: The underlying pathophysiology of idiopathic REM sleep behavior disorder (iRBD) is not fully understood, although the condition is currently recognized as an early-stage alpha-synuclein disorder. We evaluated the morbidity, mortality, and rate of conversion to a neurodegenerative disorder in a national group of patients. Methods: All patients in Denmark with a diagnosis of RBD between 2006 and 2013 were identified from the Danish National Patient Registry (NPR) records. We excluded patients who had received a diagnosis of narcolepsy or any of the following neurodegenerative diseases before their diagnosis of RBD: Parkinson’s disease, multiple system atrophy, progressive supranuclear paralysis, Alzheimer’s, and Lewy body dementia. We used randomly chosen controls matched for age, gender, and municipality. Results: In total, 246 iRBD patients and 982 matched controls were analyzed. The mortality rate was the same in both groups. The morbidity rate was significantly higher in the years before and after an RBD diagnosis, due to a wide variety of disorders in the following major disease groups: mental/behavioral disorders; endocrine/metabolic diseases; diseases of the eye; diseases of the nervous, digestive, musculoskeletal, circulatory, and respiratory systems; abnormal findings not classified elsewhere; external causes; and factors influencing health status. The conversion rate from RBD to a neurodegenerative disease was 13% over the 8 years after a diagnosis of RBD. Conclusions: A diagnosis of RBD is associated with increased morbidity several years before and after a diagnosis is made. Patients have a higher risk of converting to a neurodegenerative disorder than matched controls. Mortality rates are unchanged.

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123I-MIBG Cardiac Scintigraphy Provides Clues to the Underlying Neurodegenerative Disorder in Idiopathic REM Sleep Behavior Disorder

SLEEP ◽

10.1093/sleep/31.5.717 ◽

2008 ◽

Vol 31 (5) ◽

pp. 717-723 ◽

Cited By ~ 85

Author(s):

Tomoyuki Miyamoto ◽

Masayuki Miyamoto ◽

Keisuke Suzuki ◽

Momoka Nishibayashi ◽

Masaoki Iwanami ◽

...

Keyword(s):

Rem Sleep ◽

Neurodegenerative Disorder ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Sleep Behavior

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Faculty Opinions recommendation of Neurodegenerative disorder risk in idiopathic REM sleep behavior disorder: study in 174 patients.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718294332.793529097 ◽

2017 ◽

Author(s):

Wolfgang Oertel

Keyword(s):

Rem Sleep ◽

Neurodegenerative Disorder ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Sleep Behavior ◽

Disorder Risk

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REM Sleep without atonia correlates with abnormal vestibular-evoked myogenic potentials in isolated REM sleep behavior disorder

SLEEP ◽

10.1093/sleep/zsz128 ◽

2019 ◽

Vol 42 (9) ◽

Cited By ~ 1

Author(s):

Monica Puligheddu ◽

Michela Figorilli ◽

Alessandra Serra ◽

Ilaria Laccu ◽

Patrizia Congiu ◽

...

Keyword(s):

Rem Sleep ◽

Neurodegenerative Disorder ◽

Statistical Significance ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Vestibular Evoked Myogenic Potentials ◽

Sleep Behavior ◽

Automated Method ◽

Rem Sleep Without Atonia ◽

Dat Scan

Abstract Study Objectives The neurophysiological hallmark of REM sleep behavior disorder (RBD) is loss of atonia during REM sleep. Indeed, signs and symptoms of neurodegeneration can occur after years, even decades, from its beginning. This study aimed to measure neurophysiological alterations of the brainstem that potentially correlate with the severity of atonia loss, and determining whether a prodromal neurodegenerative disorder underlines this condition when it occurs as an isolated condition (iRBD). Methods Subjects with iRBD and matched healthy controls were recruited. The study included the recording of one-night polysomnography, vestibular-evoked myogenic potentials (VEMPs), and a [123I]-FP-CIT dopamine transporter (DAT) scan. The quantification of REM sleep without atonia (RSWA) was made according to two previously published manual methods and one automated method. Results The rate of alteration of VEMPs and VEMP score were significantly higher in iRBD patients than controls. Moreover, VEMP score was negatively correlated with the automated REM atonia index; a marginal statistical significance was also reached for the positive correlation with the visual tonic electromyographic parameter, while the other correlations, including that with DAT-scan score were not statistically significant. Conclusions Brainstem neurophysiology in iRBD can be assessed by VEMPs and their alterations may possibly indicate an early expression of the neurodegenerative process underlying this disorder at the brainstem level, which awaits future longitudinal confirmation. The correlation between RSWA and VEMP alteration might also represent a prodromal aspect anticipating the possible evolution from iRBD to neurodegeneration, whereas DAT-scan abnormalities might represent a later step in this evolution.

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Facilitatory/inhibitory intracortical imbalance in REM sleep behavior disorder: early electrophysiological marker of neurodegeneration?

SLEEP ◽

10.1093/sleep/zsz242 ◽

2019 ◽

Cited By ~ 4

Author(s):

Giuseppe Lanza ◽

Debora Aricò ◽

Bartolo Lanuzza ◽

Filomena Irene Ilaria Cosentino ◽

Mariangela Tripodi ◽

...

Keyword(s):

Rem Sleep ◽

Neurodegenerative Disorder ◽

Motor Evoked Potentials ◽

Short Interval ◽

Rem Sleep Behavior Disorder ◽

Behavior Disorder ◽

Silent Period ◽

Sleep Behavior ◽

Asymptomatic Patients ◽

Resting Motor Threshold

Abstract Study Objectives Previous studies found an early impairment of the short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) to transcranial magnetic stimulation (TMS) in Parkinson’s disease. However, very little is known on the TMS correlates of rapid eye movement (REM) sleep behavior disorder (RBD), which can precede the onset of a α-synucleinopathy. Methods The following TMS measures were obtained from 14 de novo patients with isolated RBD and 14 age-matched healthy controls: resting motor threshold, cortical silent period, latency and amplitude of the motor evoked potentials, SICI, and ICF. A cognitive screening and a quantification of subjective sleepiness (Epworth Sleepiness Scale [ESS]) and depressive symptoms were also performed. Results Neurological examination, global cognitive functioning, and mood status were normal in all participants. ESS score was higher in patients, although not suggestive of diurnal sleepiness. Compared to controls, patients exhibited a significant decrease of ICF (median 0.8, range 0.5–1.4 vs. 1.9, range 1.4–2.3; p < 0.01) and a clear trend, though not significant, towards a reduction of SICI (median 0.55, range 0.1–1.4 vs. 0.25, range 0.1–0.3), with a large effect size (Cohen’s d: −0.848). REM Sleep Atonia Index significantly correlated with SICI. Conclusions In still asymptomatic patients for a parkinsonian syndrome or neurodegenerative disorder, changes of ICF and, to a lesser extent, SICI (which are largely mediated by glutamatergic and GABAergic transmission, respectively) might precede the onset of a future neurodegeneration. SICI was correlated with the muscle tone alteration, possibly supporting the proposed RBD model of retrograde influence on the cortex from the brainstem.

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