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Background: Parkinson's disease (PD) is a common neurodegenerative disorder that is predominantly known for its motor symptoms but is also accompanied by non-motor symptoms, including anxiety. Objective: The underlying neurobiological substrates and brain network changes associated with comorbid anxiety in PD require further exploration. Methods: An analysis of oscillation-specific nodal properties in patients with and without anxiety was conducted using resting-state functional magnetic resonance imaging (rs-fMRI) and graph theory. We used a band-pass filtering approach to differentiate oscillatory frequency bands for subsequent functional connectivity (FC) and graph analyses. Results: The study included 68 non-anxiety PD (naPD) patients, 62 anxiety PD (aPD) patients, and 64 healthy controls (NC). Analyses of nodal betweenness centrality (BC), degree centrality (DC), and efficiency were conducted across multiple frequency bands. The findings indicated no significant differences in BC among naPD, aPD, and NC within the 0.01–0.08 Hz frequency range. However, we observed a specific reduction in BC at narrower frequency ranges in aPD patients, as well as differing patterns of change in DC and efficiency, which are believed to reflect the neurophysiological bases of anxiety symptoms in PD. Conclusions: Differential oscillation-specific nodal characteristics have been identified in PD patients with anxiety, suggesting potential dysregulations in brain network dynamics. These findings emphasize the complexity of brain network alterations in anxiety-associated PD and identify oscillatory frequencies as potential biomarkers. The study highlights the importance of considering oscillatory frequency bands in the analysis of brain network changes. [ABSTRACT FROM AUTHOR]

Background: Anxiety is one of the most common and disturbing non-motor symptoms of Parkinson's disease (PD). However, few studies have explored the relationship between functional connectivity (FC) and the rate of anxiety improvement after subthalamic nucleus deep brain stimulation (STN-DBS). Therefore, in this study, we aimed to explore the correlation between FC and the rate of anxiety improvement in patients with PD who underwent STN-DBS.Methods: The resting-state functional magnetic resonance imaging (rs-fMRI) data of 62 patients with anxious PD (aPD), 68 patients with PD without anxiety (naPD), and 64 healthy controls (HCs) were analyzed according to FC. Intergroup comparison and correlation analyses of anxiety improvement rates were performed.Results: The HC, aPD and naPD groups of zFCs were then used for the ANOVA test, and the results were FDR-corrected. There were 24 significant differences in FCs between the three groups. Post tests were conducted between groups found that 15 significantly different FCs were observed between the naPD and aPD groups. In addition, the two FCs in patients with aPD were significantly correlated with the rate of improvement in anxiety.Conclusion: We found that the two FCs in patients with aPD (olfactory cortex and inferior frontal gyrus [IFG] pars orbitalis; inferior temporal gyrus and posterior orbital gyrus) were significantly correlated with the rate of improvement in anxiety. Our study may help us understand the underlying mechanisms by which STN-DBS improves anxiety in PD patients and identify more effective treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) represents one of the most frequently seen neurodegenerative disorders, while anxiety accounts for its non-motor symptom (NMS), and it has greatly affected the life quality of PD cases. Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) can effectively treat PD. This study aimed to develop a clinical prediction model for the anxiety improvement rate achieved in PD patients receiving STN-DBS. Methods: The present work retrospectively enrolled 103 PD cases undergoing STN-DBS. Patients were followed up for 1 year after surgery to analyze the improvement in HAMA scores. Univariate and multivariate logistic regression were conducted to select factors affecting the Hamilton Anxiety Scale (HAMA) improvement. A nomogram was established to predict the likelihood of achieving anxiety improvement. Receiver operating characteristic (ROC) curve analysis, decision curve analysis (DCA), and calibration curve analysis were conducted to verify nomogram performance. Results: The mean improvement in HAMA score was 23.9% in 103 patients; among them, 68.9% had improved anxiety, 25.2% had worsened (Preop) anxiety, and 5.8% had no significant change in anxiety. Education years, UPDRS-III preoperative score, and HAMA preoperative score were independent risk factors for anxiety improvement. The nomogram-predicted values were consistent with real probabilities. Conclusions: Collectively, a nomogram is built in the present work for predicting anxiety improvement probability in PD patients 1 year after STN-DBS. The model is valuable for determining expected anxiety improvement in PD patients undergoing STN-DBS. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease is a common neurodegenerative disease, with depression being a common non-motor symptom. Bilateral subthalamic nucleus deep brain stimulation is an effective method for the treatment of Parkinson's disease. Thus, this study aimed to establish a nomogram of the possibility of achieving a better depression improvement rate after subthalamic nucleus deep brain stimulation in patients with Parkinson's disease. Methods: We retrospectively analyzed 103 patients with Parkinson's disease who underwent subthalamic nucleus deep brain stimulation and were followed up for the improvement of their Hamilton Depression scale scores 1 year postoperatively. Univariate and multivariate logistic regression analyses were used to select factors affecting the improvement rate of depression. A nomogram was then developed to predict the possibility of achieving better depression improvement. Furthermore, the discrimination and fitting performance was evaluated using a calibration diagram, receiver operating characteristics, and decision curve analysis. Results: The mean and median improvement rates of Hamilton Depression scores were 13.1 and 33.3%, respectively. Among the 103 patients, 70.8% had an improved depression, 23.3% had a worsened depression, and 5.8% remained unchanged. Logistic multivariate regression analysis showed that age, preoperative Parkinson's Disease Questionnaire, Hamilton Anxiety, and Hamilton Depression scores were independent factors for the possibility of achieving a better depression improvement rate. Based on these results, a nomogram model was developed. The nomogram had a C-index of 0.78 (95% confidence interval: 0.69–0.87) and an area under the receiver operating characteristics of 0.78 (95% confidence interval: 0.69–0.87). The calibration plot and decision curve analysis further demonstrated goodness-of-fit between the nomogram predictions and actual observations. Conclusion: We developed a nomogram to predict the possibility of achieving good depression improvement 1 year after subthalamic nucleus deep brain stimulation in patients with Parkinson's disease, which showed a certain value in judging the expected depression improvement of these patients. [ABSTRACT FROM AUTHOR]

To study the feasibility of plasma extracellular vesicles (EVs) miRNAs as diagnostic biomarkers for Parkinson's disease (PD). Plasma EVs were isolated from 30 PD patients and 30 age- and sex-matched healthy controls. Plasma EVs miRNAs were analysed by qRT-PCR. SH-SY5Y cells were induced by different concentrations of 1-Methyl-4-phenil-pyridinium (MPP+) to obtain PD cellular model. The levels of miRNAs and α-synuclein (α-syn) in PD cellular model were analysed by qRT-PCR and Western blot. Receiver operating characteristic (ROC) curve analysis was performed to determine the diagnostic usefulness of the miRNAs in plasma EVs for PD. The gene ontology (GO) and KEGG pathways of the target genes of miRNAs were analysed by softwares. The level of hsa-miR-30c-2-3p in plasma EVs was significantly higher in PD patients than that in controls, and the levels of hsa-miR-15b-5p, hsa-miR-138-5p, hsa-miR-338-3p, hsa-miR-106b-3p and hsa-miR-431-5p in plasma EVs were lower in PD patients than that in controls. When compared with the control group, the area under the curve (AUC) values for hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p, hsa-miR-431-5p, hsa-miR-338-3p and hsa-miR-106b-3p were all greater than 0.6. The target genes of hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p and hsa-miR-338-3p were enriched in dopaminergic synapse and PD pathway. The hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p, hsa-miR-106b-3p, hsa-miR-338-3p and hsa-miR-431-5p may be used as potential biomarkers for the diagnosis of PD, and the combined diagnostic accuracy of hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p and hsa-miR-106b-3p was better. The target genes of hsa-miR-15b-5p, hsa-miR-30c-2-3p, hsa-miR-138-5p and hsa-miR-338-3p may regulate the expression of dopamine by dopaminergic synapse and PD pathway. Isolation and identification of plasma EVs. The miRNAs in plasma EVs may be used as potential biomarkers for the diagnosis of PD. When SH-SY5Y cells were induced by different concentrations of MPP+, the levels of miRNAs and α-syn changed gradually. The target genes of miRNAs were enriched in dopaminergic synapse and PD pathway. The target genes of miRNAs may regulate the expression of dopamine. [ABSTRACT FROM AUTHOR]

Objective: Programming plays an important role in the outcome of deep brain stimulation (DBS) for Parkinson's disease (PD). This study introduced a new application for functional zonal image reconstruction in programming. Methods: Follow-up outcomes were retrospectively compared, including first programming time, number of discomfort episodes during programming, and total number of programming sessions between patients who underwent image-reconstruction-guided programming and those who underwent conventional programming. Data from 142 PD patients who underwent subthalamic nucleus (STN)-DBS between January 2017 and June 2019 were retrospectively analyzed. There were 75 conventional programs and 67 image reconstruction-guided programs. Results: At 1-year follow-up, there was no significant difference in the rate of stimulus improvement or superposition improvement between the two groups. However, patients who underwent image reconstruction-guided programming were significantly better at the first programming time, number of discomfort episodes during programming, and total number of programming sessions than those who underwent conventional programming. Conclusion: Imaging-guided programming of directional DBS leads was possible and led to reduced programming time and reduced patient side effects compared with conventional programming. [ABSTRACT FROM AUTHOR]

Purpose: Parkinson's disease (PD) is a common neurodegenerative disease, for which cognitive impairment is a non-motor symptom (NMS). Bilateral subthalamic nucleus deep brain stimulation (STN-DBS) is an effective treatment for PD. This study established a nomogram to predict cognitive improvement rate after STN-DBS in PD patients. Methods: We retrospectively analyzed 103 PD patients who underwent STN-DBS. Patients were followed up to measure improvement in MoCA scores one year after surgery. Univariate and multivariate logistic regression analyses were used to identify factors affecting improvement in cognitive status. A nomogram was developed to predict this factor. The discrimination and fitting performance were evaluated by receiver operating characteristics (ROC) analysis, calibration diagram, and decision curve analysis (DCA). Results: Among 103 patients, the mean improvement rate of the MoCA score was 37.3% and the median improvement rate was 27.3%, of which 64% improved cognition, 27% worsened cognition, and 8.7% remained unchanged. Logistic multivariate regression analysis showed that years of education, UPDRSIII drug use, MoCA Preop, and MMSE Preop scores were independent factors affecting the cognitive improvement rate. A nomogram model was subsequently developed. The C-index of the nomogram was 0.98 (95%CI, 0.97–1.00), and the area under the ROC was 0.98 (95%CI 0.97–1.00). The calibration plot and DCA demonstrated the goodness-of-fit between nomogram predictions and actual observations. Conclusion: Our nomogram could effectively predict the possibility of achieving good cognitive improvement one year after STN-DBS in patients with PD. This model has value in judging the expected cognitive improvement of patients with PD undergoing STN-DBS. [ABSTRACT FROM AUTHOR]

Background: Main motor characteristics in Parkinson's disease (PD) include bradykinesia, rigidity, and tremors. With the development of neuromodulation techniques, it has become possible to use deep brain stimulation (DBS) to control the symptoms of PD. However, since the subthalamic nucleus(STN) and globus pallidus interna (GPi) DBS have their own advantages and disadvantages, it is difficult to control symptoms of the patients. It is essential to find new stimulation methods. Case Presentation: A 33-year-old male PD patient with onset at the age of 12 years. The onset of the disease is presented with bradykinesia and progressively developed severe choreic dyskinesia with the use of medications. We then performed a thorough evaluation of the patient and decided to perform bilateral globus pallidus interna combined with subthalamic nucleus variable frequency DBS (bSGC-DBS) implantation, and after 2 years of follow-up the patient's bradykinesia and dyskinesia symptoms and quality of life improved significantly. Conclusions: This is the first case of bSCG-DBS in a PD patient with refractory dyskinesia, and the first report of encouraging results from this clinical condition. This important finding explores multi-electrode and multi-target stimulation for the treatment of dystonia disorders. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a common neurodegenerative disorder. The main neuropathological features of PD are the loss of dopaminergic neurons in the substantia nigra striata and the extensive accumulation of α-synuclein in different brain regions. The substantia nigra and striatum are brain regions with high expression of cannabinoid receptors, and the role of the endogenous cannabinoid system (ECS) has been explored in PD. The ECS may be a promising target for the treatment of PD. The correlation between PD and serum uric acid levels has been demonstrated in a large number of studies, but a causal relationship between the two has not been proven. Xanthine and hypoxanthine are upstream metabolite of uric acid, and they have been shown to be effective in relieving PD symptoms. Therefore, we hypothesized that xanthine or hypoxanthine or both may increase the inhibitory properties of GABAergic neurons by increasing the sensitivity of cannabinoid receptors on GABAergic neurons in the striatum, thereby activating the direct nigrostriatal pathway to ameliorate Parkinson's disease symptoms. The proposed hypothesis can be tested in animal and cellular intervention experiments. If this approach is found to be effective in improving PD symptoms with minimal adverse events, exogenous supplementation of xanthine/ hypoxanthine or the use of xanthine oxidase to block its metabolism to elevate hypoxanthine levels could potentially be an effective addition to PD therapy. [ABSTRACT FROM AUTHOR]

Purpose: Parkinson's disease is a progressive disorder. To investigate the biochemical alterations in the striatum of rats with different stages of Parkinson's disease induced by proteasomal inhibition, we quantified neurochemical profiles of the striatum using proton magnetic resonance spectroscopyusing 9.4 T ultra-high field imaging. Methods: In this study, 10 μg/2 μl lactacystin, a selective proteasome inhibitor, was unilaterally injected stereotaxically into the left substantia nigra pars compacta of rats. An equal volume of saline was injected into the same region and side in the control group. Changes in motor behaviour were observed. The morphological changes of tyrosine hydroxylase-positive cells in substantia nigra pars compacta were visualized using immunohistochemistry. Tyrosine hydroxylase-positive nerve fibers were quantified. Alterations of N-acetylaspartate, choline, creatine, taurine in the different stages of Parkinson's disease rats were detected using proton magnetic resonance spectroscopy. Results: Application of in vivo 1H magnetic resonance spectroscopy was repeated in both the six Parkinson's disease rats and the six control rats across three time points during the first, second and fourth weekend after administration. In Parkinson's disease rats, increased N-acetylaspartate and decreased taurine concentrations were observed in the left striatum at the first week after administration. The increased N-acetylaspartate and choline concentrations were observed at the second weekend. At the fourth weekend, increased creatine concentrations in the left side were observed, while other metabolites were not significantly changed. Conclusions: Neurochemical alterations occurred in the striatum during different stages of the Parkinson's disease model in rats. Also, 9.4 T 1H magnetic resonance spectroscopy may be a useful tool for elucidating the progression of Parkinson's disease through the variation of these metabolites. [ABSTRACT FROM AUTHOR]

The potential value of cerebral dopamine neurotrophic factor (CDNF) in treating Parkinson's disease (PD) remains controversial. To evaluate the therapeutic effects of CDNF-expressing bone marrow derived mesenchymal stem cell (CDNF-MSCs) injections in a rat model of Parkinson's disease, we chose three different routes of CDNF-MSC administration, including intra-striatal, intra-ventricular, and intravenous pathways. Parkinsonism was induced by intra-striatal unilateral injection of 6-OHDA and then rats were subsequently randomized into three groups for either intra-striatal, intra-ventricular or intravenous injection for CDNF-MSC grafting. Therapeutic effects were evaluated by observing dopaminergic (DA) neurons both in the substantia nigra compacta (SNc) and within the striatum and by monitoring apomorphine-induced rotational behavior (circling). Data show that one intra-venous administration of CDNF-MSCs was ineffective for treating Parkinson's disease-like neurodegeneration. Conversely, intra-striatal grafts can reduce loss of DA neurons both in the SNc and striatum with improvement of Parkinson's-related behaviors, compared to intra-ventricular injections. Thus, intra-striatal grafts composed of CDNF-MSCs may provide a strategy for therapeutic delivery to treat PD. [ABSTRACT FROM AUTHOR]