Nigrostriatal degeneration and altered corticostriatal functional connectivity in REM sleep behavior disorder with subtle motor dysfunction

2017 ◽  
Vol 381 ◽  
pp. 1049
Author(s):  
G. Yamada ◽  
Y. Ueki ◽  
T. Oguri ◽  
N. Oishi ◽  
A. Fukui ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Rem Sleep ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Motor Dysfunction ◽  
Sleep Behavior ◽  
Nigrostriatal Degeneration

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 Reduced striatal vesicular monoamine transporter 2 in REM sleep behavior disorder: imaging prodromal parkinsonism

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Leah C. Beauchamp ◽  
Victor L. Villemagne ◽  
David I. Finkelstein ◽  
Vincent Doré ◽  
Ashley I. Bush ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Time Window ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Vesicular Monoamine Transporter ◽  
Motor Symptoms ◽  
Monoamine Transporter ◽  
Sleep Behavior ◽  
Nigrostriatal Degeneration ◽  
Non Motor Symptoms

Abstract Motor deficits in parkinsonism are caused by degeneration of dopaminergic nigral neurons. The success of disease-modifying therapies relies on early detection of the underlying pathological process, leading to early interventions in the disease phenotype. Healthy (n = 16), REM sleep behavior disorder (RBD) (n = 14), dementia with Lewy bodies (n = 10), and Parkinson’s disease (PD) (n = 20) participants underwent 18F-AV133 vesicular monoamine transporter type-2 (VMAT2) PET to determine the integrity of the nigrostriatal pathway. Clinical, neurophysiological and neuropsychological testing was conducted to assess parkinsonian symptoms. There was reduced VMAT2 levels in RBD participants in the caudate and putamen, indicating nigrostriatal degeneration. RBD patients also presented with hyposmia and anxiety, non-motor symptoms associated with parkinsonism. 18F-AV133 VMAT2 PET allows identification of underlying nigrostriatal degeneration in RBD patients. These findings align with observations of concurrent non-motor symptoms in PD and RBD participants of the Parkinson’s Progression Markers Initiative. Together, these findings suggest that RBD subjects have prodromal parkinsonism supporting the concept of conducting neuroprotective therapeutic trials in RBD-enriched cohorts. Ongoing longitudinal follow-up of these subjects will allow us to determine the time-window of clinical progression.

scholarly journals Alterations in striato-thalamo-pallidal intrinsic functional connectivity as a prodrome of Parkinson’s disease

2017 ◽  
Author(s):  
Eran Dayan ◽  
Nina Browner
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Functional Connectivity ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Motor Dysfunction ◽  
Prodromal Phase ◽  
Sleep Behavior ◽  
Functional Connections ◽  
Input And Output

AbstractAlthough the diagnosis of Parkinson’s disease (PD) remains anchored around the cardinal motor symptoms of bradykinesia, rest tremor, rigidity and postural instability, it is becoming increasingly clear that the clinical phase of the disease is preceded by a long period of neurodegeneration, which is not readily evident in terms of motor dysfunction. The neurobiological mechanisms that underpin this prodromal phase of PD remain poorly understood. Based on converging evidence of basal ganglia (BG) dysfunction in early PD, we set out to establish whether the prodromal phase of the disease is characterized by alterations in functional communication within the input and output structures of the BG. We analyzed resting-state functional MRI data collected from patients with REM sleep behavior disorder (RBD) and/or hyposmia, two of the strongest markers of prodromal PD, in comparison to age-matched controls. Relative to controls, subjects in the prodromal group showed reduced intra- and interhemispheric functional connectivity in a striato-thalamo-pallidal network. Functional connectivity alterations were restricted to the BG and did not extend to functional connections with the cortex. The data suggest that local interactions between input and output BG structures may be disrupted already in the prodromal phase of PD.

scholarly journals Altered functional connectivity in lesional peduncular hallucinosis with REM sleep behavior disorder

Cortex ◽  
2016 ◽  
Vol 74 ◽  
pp. 96-106 ◽  
Author(s):  
Maiya R. Geddes ◽  
Yanmei Tie ◽  
John D.E. Gabrieli ◽  
Scott M. McGinnis ◽  
Alexandra J. Golby ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Rem Sleep ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Sleep Behavior ◽  
Peduncular Hallucinosis

Dynamic functional connectivity changes in Parkinson’s disease patients with REM sleep behavior disorder

2021 ◽  
pp. 147477
Author(s):  
Caiting Gan ◽  
Kewei Ma ◽  
Lina Wang ◽  
Qianqian Si ◽  
Min Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Functional Connectivity ◽  
Rem Sleep ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Dynamic Functional Connectivity ◽  
Sleep Behavior

scholarly journals Rare PSAP variants and possible interaction with GBA in REM sleep behavior disorder

2021 ◽  
Author(s):  
Yuri L. Sosero ◽  
Eric Yu ◽  
Mehrdad A. Estiar ◽  
Kheireddin Mufti ◽  
Uladzislau Rudakou ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Genetic Interaction ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Motor Dysfunction ◽  
Clinical Markers ◽  
Loss Of Function ◽  
Sleep Behavior ◽  
Saposin C

PSAP encodes saposin C, the co-activator of glucocerebrosidase, encoded by GBA. Since GBA mutations are associated with idiopathic/isolated REM sleep behavior disorder (iRBD), a prodromal stage of synucleinopathy, we examined the role of PSAP mutations in iRBD. We fully sequenced PSAP and performed Optimized Sequence Kernel Association Test in 1,113 iRBD patients and 2,324 controls. We identified loss-of-function (LoF) mutations, which are very rare in PSAP, in three iRBD patients and none in controls (uncorrected p=0.018). Two variants were stop mutations, p.Gln260Ter p.Glu166Ter, and one was an in-frame deletion, p.332_333del. All three mutations have a deleterious effect on saposin C, based on in silico analysis. In addition, the two carriers of p.Glu166Ter and p.332_333del mutations also carried a GBA variant, p.Arg349Ter and p.Glu326Lys, respectively. The co-occurrence of these extremely rare PSAP LoF mutations in two (0.2%) GBA variant carriers in the iRBD cohort, is unlikely to occur by chance (estimated co-occurrence in the general population based on gnomAD data is 0.00035%). Although none of the three iRBD patients with PSAP LoF mutations have phenoconverted to an overt synucleinopathy at their last follow-up, all manifested initial signs suggestive of motor dysfunction, two were diagnosed with mild cognitive impairment and all showed prodromal clinical markers other than RBD. Their probability of prodromal PD, according to the Movement Disorder Society research criteria was 98% or more. These results suggest a possible role of PSAP variants in iRBD and potential genetic interaction with GBA, which requires additional studies.

scholarly journals Nigrostriatal Dopaminergic Dysfunction and Altered Functional Connectivity in REM Sleep Behavior Disorder With Mild Motor Impairment

2019 ◽  
Vol 10 ◽  
Author(s):  
Gohei Yamada ◽  
Yoshino Ueki ◽  
Naoya Oishi ◽  
Takuya Oguri ◽  
Ayako Fukui ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Rem Sleep ◽  
Motor Impairment ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Sleep Behavior ◽  
Dopaminergic Dysfunction

Altered insular functional connectivity in isolated REM sleep behavior disorder: a data-driven functional MRI study

2021 ◽  
Author(s):  
Jung-Ick Byun ◽  
Kwang Su Cha ◽  
Minah Kim ◽  
Woo-Jin Lee ◽  
Han Sang Lee ◽  
...  
Keyword(s):  
Functional Connectivity ◽  
Functional Mri ◽  
Rem Sleep ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Data Driven ◽  
Sleep Behavior ◽  
Mri Study

scholarly journals Disruption of posterior brain functional connectivity and its relation to cognitive impairment in idiopathic REM sleep behavior disorder

2020 ◽  
Vol 25 ◽  
pp. 102138 ◽  
Author(s):  
A. Campabadal ◽  
A. Abos ◽  
B. Segura ◽  
M. Serradell ◽  
C. Uribe ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Functional Connectivity ◽  
Rem Sleep ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Sleep Behavior ◽  
Brain Functional Connectivity
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