scholarly journals Respiratory dysfunction in Parkinson's disease: a narrative review

2020 ◽  
Vol 6 (4) ◽  
pp. 00165-2020
Author(s):  
Andrea D'Arrigo ◽  
Stefano Floro ◽  
Francesca Bartesaghi ◽  
Chiara Casellato ◽  
Giuseppe Francesco Sferrazza Papa ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protective Factors ◽  
Respiratory Symptoms ◽  
Current Knowledge ◽  
Atypical Parkinsonism ◽  
Ventilatory Control ◽  
Respiratory Dysfunction ◽  
Pathogenetic Mechanisms ◽  
The Impact

The presence of respiratory symptoms in Parkinson's disease (PD) has been known since the first description of the disease, even though the prevalence and incidence of these disturbances are not well defined. Several causes have been reported, comprising obstructive and restrictive pulmonary disease and changes in the central ventilatory control, and different pathogenetic mechanisms have been postulated accordingly. In our review, we encompass the current knowledge about respiratory abnormalities in PD, as well as the impact of anti-Parkinsonian drugs as either risk or protective factors. A description of putative pathogenetic mechanisms is also provided, and possible treatments are discussed, focusing on the importance of recognising and treating respiratory symptoms as a key manifestation of the disease itself. A brief description of respiratory dysfunctions in atypical Parkinsonism, especially α-synucleinopathies, is also provided.

scholarly journals Clinical and Genetic Analysis of Costa Rican Patients With Parkinson's Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Gabriel Torrealba-Acosta ◽  
Eric Yu ◽  
Tanya Lobo-Prada ◽  
Javier Ruíz-Martínez ◽  
Ana Gorostidi-Pagola ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Protective Factors ◽  
Latin American ◽  
Coffee Consumption ◽  
Risk And Protective Factors ◽  
Costa Rican ◽  
European Ancestry ◽  
Compound Heterozygous ◽  
Atypical Parkinsonism

Background: Most research in genomics of Parkinson's disease (PD) has been done in subjects of European ancestry, leading to sampling bias and leaving Latin American populations underrepresented. We sought to clinically characterize PD patients of Costa Rican origin and to sequence familial PD and atypical parkinsonism-associated genes in cases and controls.Methods: We enrolled 118 PD patients with 97 unrelated controls. Collected information included demographics, exposure to risk and protective factors, and motor and cognitive assessments. We sequenced coding and untranslated regions in familial PD and atypical parkinsonism-associated genes including GBA, SNCA, VPS35, LRRK2, GCH1, PRKN, PINK1, DJ-1, VPS13C, and ATP13A2.Results: Mean age of PD probands was 62.12 ± 13.51 years; 57.6% were male. The frequency of risk and protective factors averaged ~45%. Physical activity significantly correlated with better motor performance despite years of disease. Increased years of education were significantly associated with better cognitive function, whereas hallucinations, falls, mood disorders, and coffee consumption correlated with worse cognitive performance. We did not identify an association between tested genes and PD or any damaging homozygous or compound heterozygous variants. Rare variants in LRRK2 were nominally associated with PD; six were located between amino acids p.1620 and 1623 in the C-terminal-of-ROC (COR) domain of Lrrk2. Non-synonymous GBA variants (p.T369M, p.N370S, and p.L444P) were identified in three healthy individuals. One PD patient carried a pathogenic GCH1 variant, p.K224R.Discussion: This is the first study that describes sociodemographics, risk factors, clinical presentation, and genetics of Costa Rican patients with PD, adding information to genomics research in a Latino population.

Coexistent Osteoarthritis and Parkinson’s Disease: Data from the Parkinson’s Foundation Outcomes Project

2020 ◽  
Vol 10 (4) ◽  
pp. 1601-1610
Author(s):  
Jaimie A. Roper ◽  
Abigail C. Schmitt ◽  
Hanzhi Gao ◽  
Ying He ◽  
Samuel Wu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Study Data ◽  
Functional Mobility ◽  
Quality Improvement Initiative ◽  
Timed Up And Go ◽  
Mobility Performance ◽  
Risk Of Mortality ◽  
The Impact

Background: The impact of concurrent osteoarthritis on mobility and mortality in individuals with Parkinson’s disease is unknown. Objective: We sought to understand to what extent osteoarthritis severity influenced mobility across time and how osteoarthritis severity could affect mortality in individuals with Parkinson’s disease. Methods: In a retrospective observational longitudinal study, data from the Parkinson’s Foundation Quality Improvement Initiative was analyzed. We included 2,274 persons with Parkinson’s disease. The main outcomes were the effects of osteoarthritis severity on functional mobility and mortality. The Timed Up and Go test measured functional mobility performance. Mortality was measured as the osteoarthritis group effect on survival time in years. Results: More individuals with symptomatic osteoarthritis reported at least monthly falls compared to the other groups (14.5% vs. 7.2% without reported osteoarthritis and 8.4% asymptomatic/minimal osteoarthritis, p = 0.0004). The symptomatic group contained significantly more individuals with low functional mobility (TUG≥12 seconds) at baseline (51.5% vs. 29.0% and 36.1%, p < 0.0001). The odds of having low functional mobility for individuals with symptomatic osteoarthritis was 1.63 times compared to those without reported osteoarthritis (p < 0.0004); and was 1.57 times compared to those with asymptomatic/minimal osteoarthritis (p = 0.0026) after controlling pre-specified covariates. Similar results hold at the time of follow-up while changes in functional mobility were not significant across groups, suggesting that osteoarthritis likely does not accelerate the changes in functional mobility across time. Coexisting symptomatic osteoarthritis and Parkinson’s disease seem to additively increase the risk of mortality (p = 0.007). Conclusion: Our results highlight the impact and potential additive effects of symptomatic osteoarthritis in persons with Parkinson’s disease.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

A New Series Of 1,3-Dimethylxanthine Based Adenosine A2a Receptor Antagonists As A Non-Dopaminergic Treatment Of Parkinson’s Disease

2020 ◽  
Vol 17 ◽  
Author(s):  
Suman Rohilla ◽  
Ranju Bansal ◽  
Puneet Chauhan ◽  
Sonja Kachler ◽  
Karl-Norbert Klotz
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Docking ◽  
Binding Affinity ◽  
Docking Studies ◽  
Binding Modes ◽  
Molecular Docking Studies ◽  
In Silico Docking ◽  
Adenosine A2a Receptor Antagonists ◽  
The Impact

Background: Adenosine receptors (AR) have emerged as competent and innovative nondopaminergic targets for the development of potential drug candidates and thus constitute an effective and safer treatment approach for Parkinson’s disease (PD). Xanthine derivatives are considered as potential candidates for the treatment Parkinson’s disease due to their potent A2A AR antagonistic properties. Objective: The objectives of the work are to study the impact of substituting N7-position of 8-m/pchloropropoxyphenylxanthine structure on in vitro binding affinity of compounds with various AR subtypes, in vivo antiparkinsonian activity and binding modes of newly synthesized xanthines with A2A AR in molecular docking studies. Methods: Several new 7-substituted 8-m/p-chloropropoxyphenylxanthine analogues have been prepared. Adenosine receptor binding assays were performed to study the binding interactions with various subtypes and perphenazine induced rat catatonia model was used for antiparkinsonian activity. Molecular docking studies were performed using Schrödinger molecular modeling interface. Results: 8-para-substituted xanthine 9b bearing an N7-propyl substituent displayed the highest affinity towards A2A AR (Ki = 0.75 µM) with moderate selectivity versus other AR subtypes. 7-Propargyl analogue 9d produced significantly longlasting antiparkinsonian effects and also produced potent and selective binding affinity towards A2A AR. In silico docking studies further highlighted the crucial structural components required to develop xanthine derived potential A2A AR ligands as antiparkinsonian agents. Conclusion: A new series of 7-substituted 8-m/p-chloropropoxyphenylxanthines having good affinity for A2A AR and potent antiparkinsonian activity has been developed.

scholarly journals Hypoxia, Acidification and Inflammation: Partners in Crime in Parkinson’s Disease Pathogenesis?

Immuno ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 78-90
Author(s):  
Johannes Burtscher ◽  
Grégoire P. Millet
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Cell Types ◽  
Brain Cell ◽  
Special Focus ◽  
Molecular Alterations ◽  
Research Fields

Like in other neurodegenerative diseases, protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation are hallmarks of Parkinson’s disease (PD). Differentiating characteristics of PD include the central role of α-synuclein in the aggregation pathology, a distinct vulnerability of the striato-nigral system with the related motor symptoms, as well as specific mitochondrial deficits. Which molecular alterations cause neurodegeneration and drive PD pathogenesis is poorly understood. Here, we summarize evidence of the involvement of three interdependent factors in PD and suggest that their interplay is likely a trigger and/or aggravator of PD-related neurodegeneration: hypoxia, acidification and inflammation. We aim to integrate the existing knowledge on the well-established role of inflammation and immunity, the emerging interest in the contribution of hypoxic insults and the rather neglected effects of brain acidification in PD pathogenesis. Their tight association as an important aspect of the disease merits detailed investigation. Consequences of related injuries are discussed in the context of aging and the interaction of different brain cell types, in particular with regard to potential consequences on the vulnerability of dopaminergic neurons in the substantia nigra. A special focus is put on the identification of current knowledge gaps and we emphasize the importance of related insights from other research fields, such as cancer research and immunometabolism, for neurodegeneration research. The highlighted interplay of hypoxia, acidification and inflammation is likely also of relevance for other neurodegenerative diseases, despite disease-specific biochemical and metabolic alterations.

Appendectomy Does Not Increase the Risk of Future Emergence of Parkinson’s Disease: A Meta-analysis

2021 ◽  
pp. 000313482198903
Author(s):  
Mitsuru Ishizuka ◽  
Norisuke Shibuya ◽  
Kazutoshi Takagi ◽  
Hiroyuki Hachiya ◽  
Kazuma Tago ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Random Effects Models ◽  
Significant Difference ◽  
The Cochrane Library ◽  
The Impact ◽  
The Relationship ◽  
Observation Period

Objective To explore the impact of appendectomy history on emergence of Parkinson’s disease (PD). Background Although there are several studies to investigate the relationship between appendectomy history and emergence of PD, the results are still controversial. Methods We performed a comprehensive electronic search of the literature (the Cochrane Library, PubMed, and the Web of Science) up to April 2020 to identify studies that had employed databases allowing comparison of emergence of PD between patients with and those without appendectomy history. To integrate the impact of appendectomy history on emergence of PD, a meta-analysis was performed using random-effects models to calculate the risk ratio (RR) and 95% confidence interval (CI) for the selected studies, and heterogeneity was analyzed using I2 statistics. Results Four studies involving a total of 6 080 710 patients were included in this meta-analysis. Among 1 470 613 patients with appendectomy history, 1845 (.13%) had emergences of PD during the observation period, whereas among 4 610 097 patients without appendectomy history, 6743 (.15%) had emergences of PD during the observation period. These results revealed that patients with appendectomy history and without appendectomy had almost the same emergence of PD (RR, 1.02; 95% CI, .87-1.20; P = .83; I2 = 87%). Conclusion This meta-analysis has demonstrated that there was no significant difference in emergence of PD between patients with and those without appendectomy history.

scholarly journals Impact of DaTscan Imaging on Clinical Decision Making in Clinically Uncertain Parkinson’s Disease

2021 ◽  
pp. 1-5
Author(s):  
Jonathan R. Isaacson ◽  
Salima Brillman ◽  
Nisha Chhabria ◽  
Stuart H. Isaacson
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Diagnosis ◽  
Clinical Decision Making ◽  
Photon Emission ◽  
Case Series ◽  
Emission Computed Tomography ◽  
Medication Therapy ◽  
Clinical Scenarios ◽  
The Impact

Background: The diagnosis of Parkinson’s disease (PD) is primarily clinical, but in cases of diagnostic uncertainty, evaluation of nigrostriatal dopaminergic degeneration (NSDD) by imaging of the dopamine transporter using DaTscan with single-photon emission computed tomography (SPECT) brain imaging may be helpful. Objective/Methods: In the current paper, we describe clinical scenarios for which DaTscan imaging was used in a prospective case series of 201 consecutive patients in whom a movement disorder specialist ordered DaTscan imaging to clarify NSDD. We describe the impact of DaTscan results on changing or confirming pre-DaTscan clinical diagnosis and on post-DaTscan treatment changes. Results/Conclusion: DaTscan imaging can be useful in several clinical scenarios to determine if NSDD is present. These include in patients with early subtle symptoms, suboptimal response to levodopa, prominent action tremor, drug-induced parkinsonism, and in patients with lower extremity or other less common parkinsonism clinical presentations. We also found DaTscan imaging to be useful to determine underlying NSDD in patients with PD diagnosis for 3-5 years but without apparent clinical progression or development of motor fluctuations. Overall, in 201 consecutive patients with clinically questionable NSDD, DaTscan was abnormal in 58.7% of patients, normal in 37.8%, and inconclusive in 3.5%. DaTscan imaging changed clinical diagnosis in 39.8% of patients and led to medication therapy changes in 70.1% of patients.

scholarly journals Validation of Cognitive Rehabilitation as a Balance Rehabilitation Strategy in Patients with Parkinson’s Disease: Study Protocol for a Randomized Controlled Trial

Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 314
Author(s):  
Aida Arroyo-Ferrer ◽  
Francisco José Sánchez-Cuesta ◽  
Yeray González-Zamorano ◽  
María Dolores del Castillo ◽  
Carolina Sastre-Barrios ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cognitive Therapy ◽  
Cognitive Processing ◽  
Processing Speed ◽  
Cognitive Rehabilitation ◽  
Neurodegenerative Disorder ◽  
Control Group ◽  
Motor Symptoms ◽  
The Impact

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. This disease is characterized by motor symptoms, such as bradykinesia, tremor, and rigidity. Although balance impairment is characteristic of advanced stages, it can be present with less intensity since the beginning of the disease. Approximately 60% of PD patients fall once a year and 40% recurrently. On the other hand, cognitive symptoms affect up to 20% of patients with PD in early stages and can even precede the onset of motor symptoms. There are cognitive requirements for balance and can be challenged when attention is diverted or reduced, linking a worse balance and a higher probability of falls with a slower cognitive processing speed and attentional problems. Cognitive rehabilitation of attention and processing speed can lead to an improvement in postural stability in patients with Parkinson’s. Methods: We present a parallel and controlled randomized clinical trial (RCT) to assess the impact on balance of a protocol based on cognitive rehabilitation focused on sustained attention through the NeuronUP platform (Neuronup SI, La Rioja, Spain) in patients with PD. For 4 weeks, patients in the experimental group will receive cognitive therapy three days a week while the control group will not receive any therapy. The protocol has been registered at trials.gov NCT04730466. Conclusions: Cognitive therapy efficacy on balance improvement may open the possibility of new rehabilitation strategies for prevention of falls in PD, reducing morbidity, and saving costs to the health care system.

scholarly journals Pallidal stimulation as treatment for camptocormia in Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yijie Lai ◽  
Yunhai Song ◽  
Daoqing Su ◽  
Linbin Wang ◽  
Chencheng Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Case Reports ◽  
Structural Connectivity ◽  
Video Recordings ◽  
Lead Placement ◽  
Pallidal Stimulation ◽  
The Impact ◽  
Deep Brain

AbstractCamptocormia is a common and often debilitating postural deformity in Parkinson’s disease (PD). Few treatments are currently effective. Deep brain stimulation (DBS) of the globus pallidus internus (GPi) shows potential in treating camptocormia, but evidence remains limited to case reports. We herein investigate the effect of GPi-DBS for treating camptocormia in a retrospective PD cohort. Thirty-six consecutive PD patients who underwent GPi-DBS were reviewed. The total and upper camptocormia angles (TCC and UCC angles) derived from video recordings of patients who received GPi-DBS were used to compare camptocormia alterations. Correlation analysis was performed to identify factors associated with the postoperative improvements. DBS lead placement and the impact of stimulation were analyzed using Lead-DBS software. Eleven patients manifested pre-surgical camptocormia: seven had lower camptocormia (TCC angles ≥ 30°; TCC-camptocormia), three had upper camptocormia (UCC angles ≥ 45°; UCC-camptocormia), and one had both. Mean follow-up time was 7.3 ± 3.3 months. GPi-DBS improved TCC-camptocormia by 40.4% (angles from 39.1° ± 10.1° to 23.3° ± 8.1°, p = 0.017) and UCC-camptocormia by 22.8% (angles from 50.5° ± 2.6° to 39.0° ± 6.7°, p = 0.012). Improvement in TCC angle was positively associated with pre-surgical TCC angles, levodopa responsiveness of the TCC angle, and structural connectivity from volume of tissue activated to somatosensory cortex. Greater improvement in UCC angles was seen in patients with larger pre-surgical UCC angles. Our study demonstrates potential effectiveness of GPi-DBS for treating camptocormia in PD patients. Future controlled studies with larger numbers of patients with PD-related camptocormia should extend our findings.

Sign in / Sign up

Export Citation Format

Share Document