scholarly journals Cholinergic relevant functional reactivity is associated with dopamine responsiveness of tremor in Parkinson’s disease

2022 ◽  
Author(s):  
Jingjing Wu ◽  
Cheng Zhou ◽  
Tao Guo ◽  
Xiaojun Guan ◽  
Ting Gao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cholinergic System ◽  
Challenge Test ◽  
Underlying Mechanism ◽  
Lasso Regression ◽  
Change Rate ◽  
Parkinsonian Tremor ◽  
Symptom Scores ◽  
Close Relationship

AbstractTremor in Parkinson’s disease (PD) has distinct responsiveness to dopamine, which is supposed not be exclusively related to dopamine deficiency but has a close relationship with cholinergic system. This phenomenon indicates that cholinergic system may be an important regulatory for distinct dopamine responsiveness of parkinsonian tremor. Through investigating the alterations of cholinergic and dopaminergic network during levodopa administration, we aimed at exploring the mechanisms of differed dopamine responsiveness of parkinsonian tremor. Fifty-two PD patients with tremor were enrolled. MRI scanning, UPDRS III and its sub-symptom scores were collected in OFF and ON status (dopaminergic challenge test). Then, patients were divided into two groups (dopamine-resistant tremor and dopamine-responsive tremor) according to the tremor change rate median score. Dopaminergic and cholinergic network were obtained. LASSO regression was conducted to identify functional connectivity with distinct reactivity during levodopa administration between groups. Afterwards, detailed group comparisons, interaction and correlation analyses were performed. The reactivity of cholinergic connectivity showed the highest possibility to distinguish two groups, especially connectivity of right basal forebrain 123 to right parietal operculum cortex (R.BF123-R.PO). After levodopa administration, connectivity of R.BF123-R.PO was decreased for dopamine-responsive tremor while which remained unchanged for dopamine-resistant tremor. The reactivity of R.BF123-R.PO was negatively correlated with tremor change rate. Reduced cholinergic connectivity to parietal operculum may be an underlying mechanism for the responsive tremor in PD and the distinct cholinergic reactivity of parietal operculum to levodopa may be a core pathophysiology for the differed DA responsiveness of tremor in PD.

scholarly journals Life with Parkinson’s Disease During the COVID-19 Pandemic: The Pressure Is “OFF”

2021 ◽  
pp. 1-5
Author(s):  
Trine HØrmann Thomsen ◽  
Susanna M. Wallerstedt ◽  
Kristian Winge ◽  
Filip Bergquist
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Symptom ◽  
Free Text ◽  
Symptom Scores ◽  
Related Quality ◽  
Health Related ◽  
Potential Impact ◽  
Swedish Cohort

People with Parkinson’s disease (PwP) have been suggested to be more vulnerable to negative psychological and psycho-social effects of the COVID-19 pandemic. Our aim was to assess the potential impact of the COVID-19 pandemic in PwP. A Danish/Swedish cohort of 67 PwP was analysed. Health-related quality of life (HRQL), depression, anxiety, apathy, sleep and motor symptom-scores were included in the analysis. Additionally, the Danish participants provided free-text descriptions of life during the pandemic. Overall, the participants reported significantly better HRQL during the COVID-19 period compared with before. Reduced social pressure may be part of the explanation. Despite worsened anxiety, night sleep improved.

Simvastatin Prevents Neurodegeneration in the MPTP Mouse Model of Parkinson’s Disease via Inhibition of A1 Reactive Astrocytes

2021 ◽  
pp. 1-8
Author(s):  
Ren-Wei Du ◽  
Wen-Guang Bu
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Underlying Mechanism ◽  
Reactive Astrocytes ◽  
Dopamine Neurons ◽  
Neuron Death ◽  
Neurologic Disorders

Emerging evidence indicates that A1 reactive astrocytes play crucial roles in the pathogenesis of Parkinson’s disease (PD). Thus, development of agents that could inhibit the formation of A1 reactive astrocytes could be used to treat PD. Simvastatin has been touted as a potential neuroprotective agent for neurologic disorders such as PD, but the specific underlying mechanism remains unclear. The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and primary astrocytes/neurons were prepared to investigate the effects of simvastatin on PD and its underlying mechanisms in vitro and in vivo. We show that simvastatin protects against the loss of dopamine neurons and behavioral deficits in the MPTP mouse model of PD. We also found that simvastatin suppressed the expression of A1 astrocytic specific markers in vivo and in vitro. In addition, simvastatin alleviated neuron death induced by A1 astrocytes. Our findings reveal that simvastatin is neuroprotective via the prevention of conversion of astrocytes to an A1 neurotoxic phenotype. In light of simvastatin favorable properties, it should be evaluated in the treatment of PD and related neurologic disorders characterized by A1 reactive astrocytes.

Apomorphine therapy: alternative initiation for patients with complex Parkinson's disease presentation

2019 ◽  
Vol 15 (6) ◽  
pp. 264-271 ◽  
Author(s):  
Jane Mills
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Infusion Pump ◽  
Challenge Test ◽  
Patient Specific ◽  
Drug Induced ◽  
Subcutaneous Infusion ◽  
Alternative Approach ◽  
User Friendly ◽  
Dose Injection

The apomorphine challenge test can be a distressing experience for some patients and, if they are not experienced, a discouraging option for some healthcare professionals (HCPs). The test is repeated exposure to bolus-dose injection of the medication to assess response and patient-specific dose before embarking on apomorphine therapy. Recent changes in prescribing of the anti-emetic domperidone (limited use because of QT prolongation), a drug which is a prerequisite for most patients embarking on therapy, has also added a possible complication. While recognising the value of the apomorphine challenge test, the author suggests an alternative approach of establishing apomorphine by subcutaneous infusion pump (SCAI) without the challenge test. This approach makes it more ‘user friendly’ for people with complex Parkinson's disease (PwPd) and their HCPs, and can eliminate the need for preloading with domperidone or other anti-emetic (if one is available in the country of practice). It is a viable option in acute situations, such as nil by mouth, surgery and oral dopamine agonist withdrawal, because of the associated harmful impulsive behaviour. Starting immediately with SCAI without the challenge test has proven both helpful and beneficial in clinical practice, especially in PwPd who have potential to abuse the intermittent injection, have complicated regimens and are vulnerable to drug-induced adverse effects. Some patients only need nocturnal infusions; injections during the night are difficult to administer and miss the objective of better sleep. Facilitating the process of initiation with the SCAI could improve uptake of this underused treatment through easier use and positive experience, and overcome the need for short- and longer-term domperidone use.

scholarly journals Deep Brain Stimulation Selection Criteria for Parkinson’s Disease: Time to Go beyond CAPSIT-PD

2020 ◽  
Vol 9 (12) ◽  
pp. 3931
Author(s):  
Carlo Alberto Artusi ◽  
Leonardo Lopiano ◽  
Francesca Morgante
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Selection Criteria ◽  
Challenge Test ◽  
Phenotypic Characterization ◽  
Motor Symptoms ◽  
Non Motor Symptoms ◽  
Deep Brain

Despite being introduced in clinical practice more than 20 years ago, selection criteria for deep brain stimulation (DBS) in Parkinson’s disease (PD) rely on a document published in 1999 called ‘Core Assessment Program for Surgical Interventional Therapies in Parkinson’s Disease’. These criteria are useful in supporting the selection of candidates. However, they are both restrictive and out-of-date, because the knowledge on PD progression and phenotyping has massively evolved. Advances in understanding the heterogeneity of PD presentation, courses, phenotypes, and genotypes, render a better identification of good DBS outcome predictors a research priority. Additionally, DBS invasiveness, cost, and the possibility of serious adverse events make it mandatory to predict as accurately as possible the clinical outcome when informing the patients about their suitability for surgery. In this viewpoint, we analyzed the pre-surgical assessment according to the following topics: early versus delayed DBS; the evolution of the levodopa challenge test; and the relevance of axial symptoms; patient-centered outcome measures; non-motor symptoms; and genetics. Based on the literature, we encourage rethinking of the selection process for DBS in PD, which should move toward a broad clinical and instrumental assessment of non-motor symptoms, quantitative measurement of gait, posture, and balance, and in-depth genotypic and phenotypic characterization.

scholarly journals Khodakarami, H., et al., Prediction of the Levodopa Challenge Test in Parkinson’s Disease Using Data from a Wrist-Worn Sensor. Sensors 2019, 19, 5153

Sensors ◽  
2020 ◽  
Vol 20 (15) ◽  
pp. 4167
Author(s):  
Hamid Khodakarami ◽  
Lucia Ricciardi ◽  
Maria Fiorella Contarino ◽  
Rajesh Pahwa ◽  
Kelly E. Lyons ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Challenge Test ◽  
Using Data

The authors wish to make the following erratum to this paper [...]

scholarly journals Positive association of Parkinson’s disease with ankylosing spondylitis: a nationwide population-based study

2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Fu-Chiang Yeh ◽  
Hsiang-Cheng Chen ◽  
Yu-Ching Chou ◽  
Cheng-Li Lin ◽  
Chia-Hung Kao ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ankylosing Spondylitis ◽  
Cox Model ◽  
Positive Association ◽  
Underlying Mechanism ◽  
Population Based ◽  
Neurodegenerative Process ◽  
Increased Risk ◽  
Using Data

Abstract Background Ankylosing spondylitis (AS) is characterized by excessive production of inflammatory cytokines. Recent evidence suggests that inflammation underlies the neurodegenerative process of Parkinson’s disease (PD). Whether AS has an influence on the development of PD is unclear. We aimed to examine a relationship, if any exists between AS and PD. Methods A population-based matched cohort study was performed using data from the 2000–2010 Taiwan National Health Insurance database. 6440 patients with AS and 25,760 randomly selected, age- and sex-matched controls were included in this study. The risk of PD in the AS cohort was evaluated by using a Cox model. Results This study revealed a positive association between AS and the risk of PD regardless of sex and age (aHR 1.75, p < .001). Particularly, AS cohort to non-AS cohort relative risk of PD significantly increased for the patients aged below 49 and above 65 years (aHR 4.70, p < .001; aHR 1.69, p < .001, respectively) and the patients with and without comorbidities (aHR 1.61, p < .001; aHR 2.71, p < .001, respectively). Furthermore, NSAID use was associated with lower risk of PD (aHR 0.69, p < .05). However, the risk of PD was higher (aHR 2.40, p < .01) in patients with AS receiving immunosuppressants than in those not receiving (aHR 1.70, p < .001). Conclusions Patients with AS had an increased risk of PD which might be related to underlying chronic inflammation. Further research is required to elucidate the underlying mechanism.

scholarly journals Prediction of the Levodopa Challenge Test in Parkinson’s Disease Using Data from a Wrist-Worn Sensor

Sensors ◽  
2019 ◽  
Vol 19 (23) ◽  
pp. 5153 ◽  
Author(s):  
Hamid Khodakarami ◽  
Lucia Ricciardi ◽  
Maria Contarino ◽  
Rajesh Pahwa ◽  
Kelly Lyons ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Challenge Test ◽  
Classification Problem ◽  
Clinical Scales ◽  
Clinically Significant ◽  
Class Labels ◽  
Using Data ◽  
Multi Class Classification ◽  
Operator Curve

The response to levodopa (LR) is important for managing Parkinson’s Disease and is measured with clinical scales prior to (OFF) and after (ON) levodopa. The aim of this study was to ascertain whether an ambulatory wearable device could predict the LR from the response to the first morning dose. The ON and OFF scores were sorted into six categories of severity so that separating Parkinson’s Kinetigraph (PKG) features corresponding to the ON and OFF scores became a multi-class classification problem according to whether they fell below or above the threshold for each class. Candidate features were extracted from the PKG data and matched to the class labels. Several linear and non-linear candidate statistical models were examined and compared to classify the six categories of severity. The resulting model predicted a clinically significant LR with an area under the receiver operator curve of 0.92. This study shows that ambulatory data could be used to identify a clinically significant response to levodopa. This study has also identified practical steps that would enhance the reliability of this test in future studies.

scholarly journals Tremor control after pallidotomy in patients with Parkinson's disease: correlation with microrecording findings

1997 ◽  
Vol 2 (3) ◽  
pp. E4 ◽  
Author(s):  
Jamal M. Taha ◽  
Jacques Favre ◽  
Thomas K. Baumann ◽  
Kim J. Burchiel
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Analog Scale ◽  
Tungsten Electrode ◽  
Drug Induced ◽  
Parkinsonian Tremor ◽  
Posteroventral Pallidotomy ◽  
Group A ◽  
The Difference ◽  
Group B

The goals of this study were to analyze the effect of pallidotomy on parkinsonian tremor and to ascertain whether an association exists between microrecording findings and tremor outcome. Forty-four patients with Parkinson's disease (PD) who had drug-induced dyskinesia, bradykinesia, rigidity, and tremor underwent posteroventral pallidotomy. Using a 1-μ-tip tungsten electrode, microrecordings were obtained through one to three tracts, starting 10 mm above the pallidal base. Tremor severity was measured on a patient-rated, 100-mm Visual Analog Scale (VAS), both preoperatively and 3 to 9 months (mean 6 months) postoperatively. Preoperatively, tremor was rated as 50 mm or greater in 24 patients (55%) and as less than 25 mm in 13 patients (30%). Postoperatively, tremor was rated as 50 mm or greater in five patients (11%) and less than 25 mm in 29 patients (66%). The difference was significant (p = 0.0001). Four patients (9%) had no postoperative tremor. Tremor improved by at least 50% in eight (80%) of 10 patients in whom tremor-synchronous cells were recorded (Group A) and in 12 (35%) of 34 patients in whom tremor-synchronous cells were not recorded (Group B). This difference was significant (p = 0.03). Tremor improved by at least 50 mm in all (100%) of the seven Group A patients with severe (>= 50 mm) preoperative tremor and in nine (53%) of 17 Group B patients with severe preoperative tremor. This difference was also significant (p = 0.05). The authors proffer two conclusions: 1) after pallidotomy, tremor improves by at least 50% in two-thirds of patients with PD who have severe (>= 50 mm on the VAS) preoperative tremor; and 2) better tremor control is obtained when tremor-synchronous cells are included in the lesion.

scholarly journals Association Between Irritable Bowel Syndrome and Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
XinYue Zhang ◽  
Zhen Svn ◽  
MengSi Liv ◽  
Yan Yang ◽  
Rui Zeng ◽  
...  
Keyword(s):  
Systematic Review ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Irritable Bowel Syndrome ◽  
Meta Analysis ◽  
Underlying Mechanism ◽  
Cochrane Library ◽  
Bowel Diseases ◽  
Newcastle Ottawa Scale ◽  
Irritable Bowel

Background: Parkinson's disease (PD) and irritable bowel syndrome (IBS) are respectively one of the most common neurodegenerative diseases and functional bowel diseases in the world. Recent studies suggest that patients with IBS seem to have a higher risk of PD, which conflicts with the result of previous meta-analysis. Therefore, the purpose of this systematic review is to evaluate all available evidence, in order to clarify the association between PD and IBS.Methods: Two reviewers independently searched the PubMed, Embase, Web of Science, and Cochrane library on April 25, 2021 to identify all records that explore the association between IBS and PD. All reports that clearly define PD and IBS and analyze the relationship between the two were included. The Newcastle-Ottawa scale was used to assess the risk of bias of included studies.Results: Five studies from four articles involving 2,044,110 subjects were included in this analysis. The pooled results demonstrated a significant association between PD and IBS (1.48; 95% CI: 1.35–1.62, P &lt; 0.001), with subtle heterogeneity (I2 = 0.0%, p = 0.585). The association was observed across genders and increased with age. However, the available evidence cannot allow a reliable analysis of the causal relationship between IBS and PD.Conclusion: This study demonstrates a higher risk of PD among subjects with IBS. Future studies are required to further clarify the causation and underlying mechanism of the association.

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