Novel biomarker signatures for idiopathic REM sleep behavior disorder

Neurology ◽  
2018 ◽  
Vol 91 (18) ◽  
pp. e1710-e1715 ◽  
Author(s):  
Stefania Mondello ◽  
Firas Kobeissy ◽  
Yehia Mechref ◽  
Jingfu Zhao ◽  
Farid R. Talih ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Clinical Decision Making ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Clinical Decision ◽  
Serum Levels ◽  
Serum Samples ◽  
Proteomics Analysis ◽  
Sleep Behavior ◽  
Altered Expression

ObjectiveTo perform a rigorous in-depth proteomics analysis to identify circulating biomarker signatures for idiopathic REM sleep behavior disorder (RBD), capable of providing new insights into the underlying pathogenic mechanisms and putative α-synuclein-related neurodegenerative processes.MethodsSerum samples from patients with idiopathic RBD (n = 9) and healthy controls (n = 10) were subjected to a thorough liquid chromatography–mass spectrometry (MS)/MS proteomics analysis using ultimate 3,000 nanoLC interfaced to an ESI-orbitrap velos. Data were analyzed with a systems biology approach to identify altered pathways in RBD.ResultsWe identified 259 proteins, 11 of which displayed significantly altered expression level in patients with RBD as compared to controls. Significant reduction in serum levels of dopamine β-hydroxylase (DBH) and vitamin D binding protein (GC) were consistent with alterations in the norepinephrinergic (NErgic) and dopaminergic systems, respectively. Additional altered protein profiles indicated that immunity, inflammation, complement, and coagulation also play a role in RBD pathophysiology.ConclusionsOur results shed light on the protein signature profile, molecular pathways, and mechanisms involved in the pathogenesis of RBD and its clinical manifestation. This knowledge opens a new avenue towards more accurate and timely diagnosis and characterization of RBD, which might ultimately translate into new therapeutic strategies with disease-modifying effects. Further evaluation of the identified markers is required to confirm their diagnostic value and potential to guide clinical decision-making.

Patients with REM sleep behavior disorder have higher serum levels of allantoin

2021 ◽  
Author(s):  
Lenka Hasíková ◽  
Jakub Závada ◽  
Tereza Serranová ◽  
Lenka Kotačková ◽  
Petr Kozlík ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Serum Levels ◽  
Sleep Behavior

scholarly journals Serum metabolic biomarkers for synucleinopathy conversion in isolated REM sleep behavior disorder

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Ariadna Laguna ◽  
Helena Xicoy ◽  
Eduardo Tolosa ◽  
Mònica Serradell ◽  
Dolores Vilas ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Predictive Models ◽  
Lewy Bodies ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Protein Glycosylation ◽  
Serum Samples ◽  
Sleep Behavior ◽  
Control Serum ◽  
Metabolic Biomarkers

AbstractIsolated rapid eye movement (REM) sleep behavior disorder (iRBD) is a prodromal stage of Lewy-type synucleinopathies (LTS), which can present either with an initial predominant parkinsonism (Parkinson’s disease (PD)) or dementia (dementia with Lewy bodies (DLB)). To provide insights into the underlying pathogenic mechanisms, the lipoprotein and protein glycosylation profile of 82 iRBD patients, collected before and/or after their conversion to an overt LTS, and 29 matched control serum samples were assessed by nuclear magnetic resonance (NMR) spectroscopy. Data were statistically analyzed to identify altered metabolites and construct predictive models. Univariant analysis detected no differences between iRBD patients with an LTS compared to controls. However, significant differences were found when the analysis distinguished between iRBD patients that manifested initially predominant parkinsonism (pre-PD) or dementia (pre-DLB). Significant differences were also found in the analysis of paired iRBD samples pre- and post-LTS diagnosis. Predictive models were built and distinguished between controls and pre-DLB patients, and between pre-DLB and pre-PD patients. This allowed a prediction of the possible future clinical outcome of iRBD patients. We provide evidence of altered lipoprotein and glycosylation profiles in subgroups of iRBD patients. Our results indicate that metabolic alterations and inflammation are involved in iRBD pathophysiology, and suggest biological differences underlying the progression of LTS in iRBD patients. Our data also indicate that profiling of serum samples by NMR may be a useful tool for identifying short-term high-risk iRBD patients for conversion to parkinsonism or dementia.

scholarly journals Sweet or Bland Dreams? Taste Loss in Isolated REM ‐Sleep Behavior Disorder and Parkinson's Disease

2021 ◽  
Author(s):  
Milan Nigam ◽  
Ines Ayadi ◽  
Camille Noiray ◽  
Ana Catarina Branquino‐Bras ◽  
Erika Herraez Sanchez ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rem Sleep ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Sleep Behavior

scholarly journals Motor Dysfunction in REM Sleep Behavior Disorder: A Rehabilitation Framework for Prodromal Synucleinopathy

2021 ◽  
pp. 154596832110112
Author(s):  
Rebekah L. S. Summers ◽  
Miriam R. Rafferty ◽  
Michael J. Howell ◽  
Colum D. MacKinnon
Keyword(s):  
Rem Sleep ◽  
Motor System ◽  
Clinical Care ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Motor Dysfunction ◽  
Motor Deficits ◽  
Sleep Behavior ◽  
Early Exercise ◽  
Extrapyramidal Signs

Parkinson disease (PD) and other related diseases with α-synuclein pathology are associated with a long prodromal or preclinical stage of disease. Predictive models based on diagnosis of idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) make it possible to identify people in the prodromal stage of synucleinopathy who have a high probability of future disease and provide an opportunity to implement neuroprotective therapies. However, rehabilitation providers may be unaware of iRBD and the motor abnormalities that indicate early motor system dysfunction related to α-synuclein pathology. Furthermore, there is no existing rehabilitation framework to guide early interventions for people with iRBD. The purpose of this work is to (1) review extrapyramidal signs of motor system dysfunction in people with iRBD and (2) propose a framework for early protective or preventive therapies in prodromal synucleinopathy using iRBD as a predictive marker. Longitudinal and cross-sectional studies indicate that the earliest emerging motor deficits in iRBD are bradykinesia, deficits performing activities of daily living, and abnormalities in speech, gait, and posture. These deficits may emerge up to 12 years before a diagnosis of synucleinopathy. The proposed rehabilitation framework for iRBD includes early exercise-based interventions of aerobic exercise, progressive resistance training, and multimodal exercise with rehabilitation consultations to address exercise prescription, progression, and monitoring. This rehabilitation framework may be used to implement neuroprotective, multidisciplinary, and proactive clinical care in people with a high likelihood of conversion to PD, dementia with Lewy bodies, or multiple systems atrophy.

scholarly journals Probable REM sleep behavior disorder is associated with longitudinal cortical thinning in Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Eun Jin Yoon ◽  
Oury Monchi
Keyword(s):  
Parkinson’S Disease ◽  
Caudate Nucleus ◽  
Rem Sleep ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Volume Changes ◽  
Sleep Behavior ◽  
Left Caudate ◽  
Left Insula ◽  
Subcortical Volume

AbstractREM sleep behavior disorder (RBD) has a poor prognostic implication in both motor and non-motor functions in Parkinson’s disease (PD) patients. However, to the best of our knowledge no study to date investigated the longitudinal cerebral changes underlying RBD symptoms in PD. We performed the longitudinal study to investigate the association between probable RBD and cortical and subcortical changes in early, de novo PD patients. We studied 78 participants from the Parkinson’s Progression Marker Initiative who underwent structural MRI at baseline and after 2 years. The presence of probable RBD (pRBD) was evaluated using the RBD screening questionnaire. We compared the cross-sectional and longitudinal cortical thickness and subcortical volume changes, between PD patients with and without pRBD. At baseline, we found bilateral inferior temporal cortex thinning in the PD-pRBD group compared with the PD-noRBD group. Longitudinally, the PD-pRBD group revealed a significant increase in the rate of thinning in the left insula compared with the PD-noRBD group, and the increased thinning correlated with decreased cognitive performance. In subcortical volume analyses, the presence of pRBD was linked with volume decrease over time in the left caudate nucleus, pallidum and amygdala. The volume changes in the left caudate nucleus revealed correlations with global cognition. These results support the idea that RBD is an important marker of rapid progression in PD motor and non-motor symptoms and suggest that the atrophy in the left insula and caudate nucleus might be the underlying neurobiological mechanisms of the poorer prognosis in PD patients with RBD.

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