Advances in Parkinson's Disease

Journal Information
ISSN / EISSN : 2169-9712 / 2169-9720
Published by: Scientific Research Publishing, Inc. (10.4236)
Total articles ≅ 84
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Zeynep Mine Altunay, Fatma Rüyal Tan, Nermin Bölükbaşı, Funda Fatma Bölükbaşı Hatip, Izzettin Hatip-Al-Khatib
Advances in Parkinson's Disease, Volume 11, pp 1-10; https://doi.org/10.4236/apd.2022.111001

Abstract:
Background: Parkinson disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms. Bladder dysfunction is the common non-motor symptom of PD, most often presenting with detrusor overactivity (DO). Treatment of DO is currently limited, poorly tolerated and sometimes ineffective. Bladder responses are not only mediated by muscarinic cholinergic receptors (mAChR) but also by nicotinic cholinergic receptors (nAChR). However, nicotinic receptor subtypes and functions in the bladder are not clearly identified. Purpose: This study aimed at investigating the effect of varenicline, an alpha7 full agonist and alpha4beta2/alpha3 partial agonist, on detrusor strips in rat PD model induced by substantia nigra injection of 6-hydroxydopamine. Method: The detrusor activity was studied in an isolated organ bath system. Results: In PD group, the detrusor activity was increased, whereas varenicline decreased the DO. Conclusion: Alpha7 nAChR agonists may have therapeutic potential in treatment of bladder overactivity in PD.
Xuezhong Li, Kun Zhao, Yuansu Zhuang, Xiaopeng Chen, Yi Liu
Advances in Parkinson's Disease, Volume 10, pp 1-13; https://doi.org/10.4236/apd.2021.101001

Abstract:
Park 7 gene encodes a conserved protein called DJ-1 protein, which involves autophagy stress, but the mechanism is unclear. Therefore, it is necessary to explore the mechanism of DJ-1 regulation PC-12 autophagical stress. Using CRISPR/Cas9 technique to construct DJ-1 knockout PC-12 cell lines, we culture wild-type and DJ-1 knockout PC-12 cell lines, establish oxidative stress cell model by MPP+, and divide them into wild-type control group (WT), wild-type intervention group (WT + MPP+), DJ-1 knockout control group (KO) and DJ-1 knockout intervention group (KO + MPP+), and explore the role of DJ-1 in regulating neuronal autophagy stress by cell viability assay, immunofluorescence, confocal, western blotting and electron microscopy. The results show that the growth ability of DJ-1 knockout cells is inferior to that of normal cells, and DJ-1 knockout cells are more sensitive to oxidative stress and more vulnerable to damage than wild-type cells. Exposing to MPP+, DJ-1 proteins undergo oxidative responses at Cys-106 sites, while DJ-1 knockout PC-12 cells do not show similar responses. The wild-type PC-12 cells have the confocal in both anti-oxidant DJ-1 antibody and anti-C-Raf phosphorylation antibody. The activated DJ-1 induces the phosphorylation of C-Raf at Ser338 sites to activate directly C-Raf, and subsequently activates ERK1/2 signaling pathways to antagonize MPP+-induced neurotoxicity. Lack of DJ-1, oxidative stress can not promote C-Raf activation. Although the phosphorylation level of cell ERK is also increased, the increase of intranucleus pERK is not obvious. Wild type and DJ-1 knockout PC-12 cells can produce autophagical stress in the face of oxidative stress, but the proportion of autophagolysosomes produced in wild type PC-12 cells is larger than that in DJ-1 knockout cells. PD98059 can reduce autophagy stress in the state of oxidative stress in wild-type PC-12 cells, and the number of autophagolysosomes is similarly reduced, while sorafenib decreased slightly DJ-1 the autophagical stress, and the proportion of autophagolysosomes decreased more. Therefore, we can infer that activated DJ-1 directly phosphorylates C-Raf at Ser-338 sites, then activating C-Raf, subsequent activation of the MEK/ERK pathway. DJ-1 promotes autophagy maturation through the C-Raf/ERK pathway, thereby improving cell survival.
Kazuo Abe
Advances in Parkinson's Disease, Volume 10, pp 15-23; https://doi.org/10.4236/apd.2021.102002

Abstract:
Consumer-wearable activity trackers have been used for monitoring health-related metrics to estimate steps, distance, physical activity, energy expenditure, and sleep. The purpose of this mini review was to summarize the evidence for validity of the most popular wrist-worn activity tracker (Fitbit) to estimate those health-related metrics in Parkinson disease. We researched full-length English studies in PubMed, Science Direct, Google Scholar, and Scopus, through September, 2021. In total, 27 studies and a textbook description were included in the review. To adapt consumer-wearable activity trackers for evaluating health-related metrics in Parkinson’s disease (PD) patients, there may be some points to be elucidated and conquered. First, measurement accuracy and precision are required. Second, inter-device reliability for measuring steps, distance, and energy expenditure must be considered. Third, wearability: there are some types of device such as wrist-worn, ankle-worn, belt-fixed, and so on. Overall, Fitbit has advantage for these points. This mini review indicates that Fitbit has enough measurement accuracy and precision to estimate health-related metrics of PD patients including amount of step, physical activity energy expenditure, and quality of sleep.
Yoshiro Fujii
Advances in Parkinson's Disease, Volume 09, pp 13-19; https://doi.org/10.4236/apd.2020.92002

Abstract:
The purpose of this study is to document the improvement observed in two cases of Parkinson’s disease (PD) after dental treatment. The first subject is a man in his 60s with severe Parkinson’s disease; medication has not been very effective in this case. Prior to treatment, he was unable to stand without support due to rigidity. Just after removing as much of the dental infection as possible, he was able to walk, albeit slowly, and as a result of continuing treatment, one month later, the symptoms had significantly improved. The second subject is a woman in her 40s, who became aware of joint stiffness seven years ago, and was later diagnosed with PD independently at three hospitals. Her main symptoms were rigidity, knee pain, and speech disorder. The dopamine medication worked well against rigidity, but the symptoms reappeared after the medication stopped working. Her condition was significantly improved just after one tooth with an apical lesion was extracted. Although the underlying mechanism has not been clarified, I hypothesize that, at least in these cases, negative signals that passed through the trigeminal nerve to the midbrain affected predominantly the dopaminergic neurons in the substantia nigra of the midbrain. Removal of the harmful signals from the oral area resulted in normalization of the substantia nigra. Further research should be promoted with dental and medical cooperation.
Robert LeMoyne, Timothy Mastroianni, Donald Whiting, Nestor Tomycz
Advances in Parkinson's Disease, Volume 09, pp 21-39; https://doi.org/10.4236/apd.2020.93003

Abstract:
Deep brain stimulation offers an advanced means of treating Parkinson’s disease in a patient specific context. However, a considerable challenge is the process of ascertaining an optimal parameter configuration. Imperative for the deep brain stimulation parameter optimization process is the quantification of response feedback. As a significant improvement to traditional ordinal scale techniques is the advent of wearable and wireless systems. Recently conformal wearable and wireless systems with a profile on the order of a bandage have been developed. Previous research endeavors have successfully differentiated between deep brain stimulation “On” and “Off” status through quantification using wearable and wireless inertial sensor systems. However, the opportunity exists to further evolve to an objectively quantified response to an assortment of parameter configurations, such as the variation of amplitude, for the deep brain stimulation system. Multiple deep brain stimulation amplitude settings are considered inclusive of “Off” status as a baseline, 1.0 mA, 2.5 mA, and 4.0 mA. The quantified response of this assortment of amplitude settings is acquired through a conformal wearable and wireless inertial sensor system and consolidated using Python software automation to a feature set amenable for machine learning. Five machine learning algorithms are evaluated: J48 decision tree, K-nearest neighbors, support vector machine, logistic regression, and random forest. The performance of these machine learning algorithms is established based on the classification accuracy to distinguish between the deep brain stimulation amplitude settings and the time to develop the machine learning model. The support vector machine achieves the greatest classification accuracy, which is the primary performance parameter, and K-nearest neighbors achieves considerable classification accuracy with minimal time to develop the machine learning model.
Makoto Shiraishi, Futaba Maki, Naoshi Sasaki, Yasuhiro Hasegawa
Advances in Parkinson's Disease, Volume 08, pp 35-41; https://doi.org/10.4236/apd.2019.83004

Abstract:
Non-ergot dopamine agonists have become popular for treating motor complications associated with long-term use of levodopa-containing drugs. We conducted a retrospective study in which we identified clinical problems related to use of non-ergot dopamine agonists. The study included 38 patients with Parkinson’s disease (PD) who suffered the wearing-off phenomenon and had thus been under non-ergot dopamine receptor agonist therapy for 1 - 2 years. Some presented with problems such as major symptoms of PD (30.3%), psychiatric symptoms (24.2%), and postural dysfunction (21.2%). Comparison between two different non-ergot drugs showed the levodopa dosage to be greater among patients taking ropinirole than among those taking pramipexole. In patients with advanced PD, various problematic symptoms can develop early after administration of a non-ergot dopamine agonist to treat the wearing-off phenomenon, necessitating identification and treatment of such symptoms on a patient-to-patient basis.
, Júlia Lajtos, József Janszky, Norbert Kovács
Advances in Parkinson's Disease, Volume 08, pp 18-34; https://doi.org/10.4236/apd.2019.82003

Abstract:
Background: Antiparkinsonian pharmacotherapy represents one of the most important expenses related to Parkinson’s disease. The application of generic drugs may help to reduce the economic burden of the disease; however, efficacy and safety of these products have been less studied. Objective: To investigate the efficacy and safety of generic rasagiline (Ralago®) from a clinical perspective. Methods: The Clinical Global Impression of Severity scale was used to rate the most important motor and non-motor symptoms at baseline and 12 weeks after the initiation of Ralago®. Patients also identified symptoms which were the main sources of their disability and distress in everyday life. Results: A total of 499 patients were enrolled (231 females, mean age: 73.2 ± 9.1 years, mean duration of disease: 3.6 ± 3.7 years). Of them, 486 patients completed the study protocol. Both motor and non-motor symptoms showed improvement during 12-week Ralago® treatment. Adverse events were rare, and the majority of them were not considered as serious. Conclusions: The generic rasagiline (Ralago®) is an effective and safe generic product.
Fatta B. Nahab, Hamad Abu-Hussain, Lissette Moreno
Advances in Parkinson's Disease, Volume 08, pp 42-61; https://doi.org/10.4236/apd.2019.83005

Abstract:
INTRODUCTION: Parkinson’s disease (PD) is a disorder characterized by complex motor and non-motor symptoms that can be difficult for patients to accurately communicate. Wearable technologies portend improvements in assessment and monitoring of these symptoms, with their clinical utility currently being evaluated in routine clinical care. OBJECTIVE: To evaluate the clinical utility of the Personal KinetiGraph® (PKG®) Movement Recording System in the routine clinical care of persons with PD (PWP). METHODS: Clinically stable, non-demented PWP presented for two routine clinic visits that included: medication review, symptom review, neurological examination including the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III/IV, and completion of a clinical management plan by a movement disorder specialist prior to review of the PKG report. After reviewing the PKG report, the clinician completed a modified clinical management plan taking into consideration the findings of the PKG. This was repeated at a second visit to evaluate various outcome measures following PKG-enhanced management. RESULTS: The PKG improved the assessment of PD symptoms and the response to treatment, while increasing patient activity levels and compliance. Clinical management plans enhanced by PKG led to different recommendations in 29.4% of cases compared with standard of care due to higher rates of bradykinesia, dyskinesia, tremor, and fluctuations identified by PKG. Using the PKG in the clinical management plan led to a change in medications in 75% (21/28) of patients and both a statistically significant difference and a clinically meaningful reduction in MDS-UPDRS III score of 4.8 (p = 0.028). Additionally, positive changes in both the clinician (17/28; 61%) and patient-reported (13/24; 54%) Global Impression of Improvement were reported. CONCLUSION: The PKG is a valuable tool in augmenting clinical management when utilized along with a clinical assessment.
, Husam A. M. Ali
Advances in Parkinson's Disease, Volume 08, pp 63-74; https://doi.org/10.4236/apd.2019.84006

Abstract:
Background: Autonomic dysfunction in idiopathic Parkinson disease is a frequent and disabling complication, with an estimated prevalence of 47% and has a significant impact on the patient’s quality of life. Objectives: The main objective of this study was to determine the frequency of autonomic dysfunction among Sudanese Parkinson patients and identify possible risk factors attribute to develop autonomic dysfunction and to assess the extent to which the progression of dysautonomia affects activities of daily living, health-related quality of life. Methods: In this descriptive perspective, cross-sectional hospital-based study, 51 patients were studied using standardized questionnaire including history and clinical examination. Results: A total of 51 patients have been examined: male to female ratio 1.5:1; mean age 55 ± 5 years; Parkinson disease duration, 7 ± 2 years. 47% of the patients had one or more symptoms of autonomic dysfunction with mean age 59 ± 10. Constipation and bloating were the most common symptoms where sweating abnormality was the least symptoms to observe. The symptom of autonomic dysfunction has been worse with disease progression in 50% of the patients and 47% of the patients reported that both motors and autonomic dysfunction symptoms were causing disability than autonomic dysfunction symptoms alone. Conclusions: The study demonstrates that autonomic dysfunction is not only common in Parkinson Disease, but it increases in severity with increasing disease stages. Older age with long disease duration was also considered along with advanced disease stages strong factors determining the presence of autonomic dysfunction. The study recommends that symptoms of autonomic dysfunction survey be a routine aspect of the evaluation of Parkinson disease patients, especially with advanced age.
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