Effects of bilateral stimulation of the subthalamic nucleus in Parkinson's disease with and without REM sleep behaviour disorder

2019 ◽  
pp. jnnp-2019-320858 ◽  
Author(s):  
Panagiotis Bargiotas ◽  
Ines Debove ◽  
Ioannis Bargiotas ◽  
Martin Lenard Lachenmayer ◽  
Maria Ntafouli ◽  
...  

BackgroundAlthough rapid eye movement sleep behaviour disorder (RBD) in Parkinson’s disease (PD) is associated with increased non-motor symptoms, its impact on the deep brain stimulation (DBS) outcome remains unclear. This is the first study to compare the post-DBS outcome between PD patients with RBD (PD-RBD+) and without (PD-RBD-).MethodsWe analysed data from PD patients who were treated with bilateral DBS in the nucleus subthalamicus. Assessments included night-polysomnography (only pre-DBS), and motor and non-motor assessments pre-DBS and post-DBS.ResultsAmong 50 PD patients (29 males, mean age 62.5 years, 11.8 mean PD years), 24 (48%) had RBD. Pre-DBS, the two groups were equal in respect to sociodemographic features, disease duration and PD medications. A multivariate analysis showed that the clinical profile linked to motor, non-motor and quality of life features differed significantly between PD patients with and without RBD. The most discriminative elements were Unified Parkinson’s Disease Rating Scale (UPDRS)-III, apathy and depression scores. Post-DBS, UPDRS-III, Epworth sleepiness scale and PD questionnaire improved significantly in both groups. UPDRS-II scores significantly improved in the PD-RBD+ group (−45%) but remained unchanged in the PD-RBD- group (−14%). The depression score improved significantly in the PD-RBD+ (−34%) and remained unchanged in the PD-RBD- group. The apathy score remained unchanged in the PD-RBD+ group but increased significantly in the PD-RBD- group (+33%).ConclusionWhile pre-DBS, PD patients with and without RBD showed different clinical profiles, post-DBS, the clinical profiles were comparable between the two groups. In respect to depressive symptoms, apathy and activities of daily living, PD-RBD+ patients show favourable post-DBS outcome. These findings highlight the importance of RBD assessment prior to DBS surgery.

Brain ◽  
2019 ◽  
Vol 142 (7) ◽  
pp. 2051-2067 ◽  
Author(s):  
Seyed-Mohammad Fereshtehnejad ◽  
Chun Yao ◽  
Amelie Pelletier ◽  
Jacques Y Montplaisir ◽  
Jean-François Gagnon ◽  
...  

Abstract Parkinson’s disease has a long prodromal stage with various subclinical motor and non-motor manifestations; however, their evolution in the years before Parkinson’s disease is diagnosed is unclear. We traced the evolution of early motor and non-motor manifestations of synucleinopathy from the stage of idiopathic rapid eye movement (REM) sleep behaviour disorder until defined neurodegenerative disease. During 2004–16, we recruited and then annually followed 154 polysomnography-proven patients with idiopathic REM sleep behaviour disorder, of whom 55 phenoconverted to defined parkinsonism or dementia. Longitudinal data on multiple prodromal features, including the Unified Parkinson’s Disease Rating Scale parts I–III, quantitative motor tests, olfaction, colour vision, cognition, and autonomic functions were gathered annually (average = five follow-up visits, range: 2–12 years). The same measures were also assessed in 102 age- and sex-matched healthy control subjects. By looking backward from the time of dementia or parkinsonism diagnosis, we examined trajectories of each prodromal feature using mixed effect models. Based on analysis, olfactory loss was first to develop, with predicted onset >20 years before phenoconversion. This was followed by impaired colour vision, constipation, and erectile dysfunction, starting 10–16 years prior to phenoconversion. At 7–9 years before phenoconversion, slight urinary dysfunction and subtle cognitive decline could be detected. Among motor symptoms altered handwriting, turning in bed, walking, salivation, speech, and facial expression began to be disrupted starting 7–11 years prior to parkinsonism diagnosis, but remained mild until soon before phenoconversion. Motor examination abnormalities began 5–7 years before phenoconversion, with the alternate tap test having the longest interval (8 years before phenoconversion). Among cardinal motor phenotypes, bradykinesia appeared first, ∼5–6 years prior to phenoconversion, followed by rigidity (Year −3) and tremor (Year −2). With direct prospective evaluation of an idiopathic REM sleep behaviour disorder cohort during phenoconversion, we documented an evolution of prodromal manifestations similar to that predicted by pathological staging models, with predicted prodromal intervals as long as 20 years.


2021 ◽  
Vol 92 (3) ◽  
pp. 271-281
Author(s):  
Zhihong Lyu ◽  
Shuxin Zheng ◽  
Xiaoyuan Zhang ◽  
Yiling Mai ◽  
Jiyang Pan ◽  
...  

Olfactory impairment and rapid eye movement sleep behaviour disorder (RBD) are prodromal symptoms of Parkinson’s disease (PD) that may be associated with each other. This review aims to investigate the significance of olfaction in the diagnosis and prognosis of patients with RBD and to assess moderating factors affecting olfactory performance. We searched articles on olfaction in RBD and PD in five electronic databases. We identified 32 studies for the systematic review and used 28 of those, including 2858 participants for meta-analysis. Results revealed significant deficits in odour identification (g=−1.80; 95% CI: −2.17 to −1.43), threshold (g=−1.29; 95% CI: −1.67 to −0.91), discrimination (g=−1.08; 95% CI: −1.28 to −0.87) and overall olfactory function (g=−1.64; 95% CI: −1.94 to −1.35) in patients with RBD. Except for the Unified Parkinson's Disease Rating Scale Part III scores, none of the known moderating variables (including age, sex, disease duration and years of education) accounted for the olfactory function heterogeneity in patients with RBD. We identified similar olfactory impairments in patients with RBD and patients with PD (either with or without underlying RBD). These findings suggest that olfactory impairment may be a sensitive and stable diagnostic biomarker of RBD and appears to be useful for identifying patients with idiopathic RBD at high risk for early conversion to PD.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giorgio Leodori ◽  
Maria Ilenia De Bartolo ◽  
Daniele Belvisi ◽  
Alessia Ciogli ◽  
Andrea Fabbrini ◽  
...  

AbstractWe aimed to investigate salivary caffeine content, caffeine absorption and metabolism in Parkinson’s disease (PD) and verify whether salivary caffeine can be used as a biomarker of PD. We enrolled 98 PD patients and 92 healthy subjects. Caffeine and its major metabolite, paraxanthine, were measured in saliva samples collected before and 4 h after the oral intake of caffeine (100 mg). We measured caffeine absorption as the normalized increase in caffeine levels, and caffeine metabolism as the paraxanthine/caffeine ratio. The Movement Disorder Society Unified Parkinson's Disease Rating Scale part III, the Hoehn & Yahr, the presence of motor complications, and levodopa equivalent dose (LED) were assessed and correlated with caffeine levels, absorption, and metabolism. The effects of demographic and environmental features possibly influencing caffeine levels were also investigated. Caffeine levels were decreased in patients with moderate/advanced PD, while caffeine levels were normal in patients with early and de-novo PD, unrelated to caffeine intake. Caffeine absorption and metabolism were normal in PD. Decreased salivary caffeine levels in PD were associated with higher disease severity, longer duration, and the presence of motor complications, no significant association was found with LED. Salivary caffeine decrease correlates with PD progression.


2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
He-Yang You ◽  
Lei Wu ◽  
Hai-Ting Yang ◽  
Chen Yang ◽  
Xiao-Ling Ding

Background. Pain is frequent in Parkinson’s disease (PD) and Parkinson-plus syndrome. This study aimed to assess the prevalence, characteristics, therapy (especially the effect of dopaminergic therapy), and associated symptoms of pain in Parkinson's disease and multiple system atrophy (MSA) patients. Methods. Seventy-one PD patients, sixty-five MSA patients, and forty age-matched healthy controls were enrolled and evaluated by using the German pain questionnaire and visual analogue scale (VAS). In addition, the influence of pain in PD patients on anxiety, depression, and the quality of life was assessed with the Hospital Anxiety and Depression Scale (HADS) and Parkinson’s Disease Questionnaire (PDQ-39). Results. Compared to that of the healthy controls, the PD and MSA patients had a significantly higher presence of pain (P<0.01, P<0.01). PD patients had a higher presence of pain than MSA patients (P=0.007). No difference in VAS scores was observed between the PD and MSA patients (P=0.148). A total of 21 PD patients (42.85%) with pain and 13 MSA patients (43.33%) with pain received treatment. A total of 13 PD patients with pain and 6 MSA patients with pain had an improved pain intensity after using dopaminergic medication. The differences in the disease duration, Hoehn and Yahr stages, and scores on the Unified Parkinson’s Disease Rating Scale motor score, HAD-D, HAD-A, and PDQ-39 were significant between the PD patients with and without pain. Conclusion. PD and MSA patients are prone to pain with insufficient treatment. Pain interventions should be provided as soon as possible to improve the patient’s life.


2020 ◽  
Vol 2 (2) ◽  
Author(s):  
Matthias Luz ◽  
Alan Whone ◽  
Niccolò Bassani ◽  
Richard K Wyse ◽  
Glenn T Stebbins ◽  
...  

Abstract There is an increasing need for improved endpoints to assess clinical trial effects in Parkinson’s disease. We propose the Parkinson’s Disease Comprehensive Response as a novel weighted composite endpoint integrating changes measured in three established Parkinson’s outcomes, including: OFF state Movement Disorder Society Unified Parkinson’s Disease Rating Scale Motor Examination scores; Motor Experiences of Daily Living scores; and total good-quality ON time per day. The data source for the initial development of the composite described herein was a recent Phase II trial of glial cell line-derived neurotrophic factor. A wide range of clinically derived relative weights was assessed to normalize for differentially scoring base rates with each endpoint component. The Parkinson’s disease comprehensive response, in contrast to examining practically defined OFF state Unified Parkinson’s Disease Rating Scale Motor Examination scores alone, showed stability over 40 weeks in placebo patients, and all 432 analyses in this permutation exercise yielded significant differences in favour of glial cell line-derived neurotrophic factor. The findings were consistent with results obtained employing three different global statistical test methodologies and with patterns of intra-patient change. Based on our detailed analyses, we conclude it worth prospectively evaluating the clinical utility, validity and regulatory feasibility of using clinically supported final Parkinson’s disease comprehensive response formulas (for both the Unified Parkinson’s Disease Rating Scale-based and Movement Disorders Society-Unified Parkinson’s Disease Rating Scale-based versions) in future disease-modifying Parkinson’s trials. Whilst the data source employed in the initial development of this weighted composite score is from a recent Phase II trial of glial cell line-derived neurotrophic factor, we wish to stress that the results are not described to provide post hoc evidence of the efficacy of glial cell line-derived neurotrophic factor but rather are presented to further the debate of how current regulatory approved rating scales may be combined to address some of the recognized limitations of using individual scales in isolation.


2016 ◽  
Vol 10 (4) ◽  
pp. 339-343 ◽  
Author(s):  
Carlos Henrique Ferreira Camargo ◽  
Rafael Arthur Serpa ◽  
Thiago Matnei ◽  
Jivago Szpoganicz Sabatini ◽  
Hélio Afonso Ghizoni Teive

ABSTRACT Background: Apathy is one of the main neuropsychiatric symptoms in patients with Parkinson's disease (PD) and is associated with Parkinson's disease dementia (PDD). Objective: To identify the characteristics of apathy in individuals with PDD according to caregiver perception. Methods: Thirty-nine patients with PD according to MDS criteria for PDD were included. The following scales were used: the Hoehn and Yahr, the Unified Parkinson's Disease Rating Scale III, Scales for Outcomes in Parkinson's Disease-Cognition (SCOPA Cog), the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Apathy Evaluation Scale (AES). Results: A total of 97.4% of the patients showed results consistent with apathy. Analysis of question 14 of the AES revealed no correlation with the total result of all the questions [r=-1293, r²=0.0167, 95%CI (-0.4274 to 0.1940), P=0.2162], however, there was a correlation of responses to the same question with depression data on the MADRS scale [r=-0.5213, r²=0.2718, 95%CI (-0.7186 to -0.2464), P=0.00033]. Conclusion: Apathy is a disorder associated with PDD. However, the scoring scheme of the AES questions can lead to different interpretations of caregiver responses, highlighting limitations of the tool for use in studies of PDD.


2021 ◽  
pp. 089198872110491
Author(s):  
Sarah K. Lageman ◽  
Emily K. Donovan ◽  
Teresita Villaseñor ◽  
Paul B. Perrin

Background: While research has demonstrated associations between Parkinson’s disease (PD) severity and caregiver burden and emotional functioning, less is known about the associations between specific PD symptom patterns and caregiver functioning. Objective: The purpose of the current study was to explore symptomatology subtypes in PD from the caregiver perspective in the U.S. and Mexico and to determine whether caregiver burden, depression, or anxiety differed by PD symptomatology subtype. Methods: Two hundred fifty-three caregivers ( M age = 59.9) completed Parts I and II of the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), the Zarit Burden Interview, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 scales. Results: Cluster analysis using domains from the MDS-UPDRS revealed 5 symptomatology subtypes: pain/motor predominant, low symptoms, severe diffuse symptoms, moderate restricted symptoms with speech/oral predominant, and mood predominant. Caregiver burden was greatest for caregivers of individuals in the severe diffuse symptom and moderate restricted symptoms with speech/oral predominant clusters. High caregiver depression and caregiver anxiety were observed in all clusters other than the low symptoms cluster. There were no site by cluster interactions, suggesting that symptom patterns contribute to caregiver functioning in similar ways in the U.S. and Mexico. Conclusions: This data-driven analysis revealed 5 symptomatology subtypes of PD from caregivers’ perspectives and highlighted the need for treatments and interventions based on predominant PD symptom expression. Importance of caregiver support across various symptomatology expressions, and particularly on specialist treatment for predominant speech/oral difficulties was recommended.


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