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Background: Deep brain stimulation (DBS) of globus pallidus interna (GPi) is an established treatment for advanced Parkinson's disease (PD). However, in contrast to subthalamic nucleus (STN)-DBS, long-term outcomes of GPi-DBS have rarely been studied., Objective: We investigated the long-term motor outcomes in PD patients at 5 years after GPi-DBS., Methods: We retrospectively analyzed the clinical data for PD patients who underwent GPi-DBS. Longitudinal changes of UPDRS scores from baseline to 5 years after surgery were assessed., Results: Forty PD patients with a mean age of 59.5 ± 7.9 years at DBS surgery (mean duration of PD: 11.4 ± 3.4 years) were included at baseline and 25 patients were included in 5-year evaluation after DBS. Compared to baseline, sub-scores for tremor, levodopa-induced dyskinesia (LID), and motor fluctuation indicated improved states up to 5 years after surgery (p < 0.001). However, UPDRS Part 3 total score and sub-score for postural instability and gait disturbance (PIGD) gradually worsened over time until 5 years after surgery (p > 0.017 after Bonferroni correction). In a logistic regression model, only preoperative levodopa response was associated with the long-term benefits on UPDRS Part 3 total score and PIGD sub-score (OR = 1.20; 95% CI = 1.04-1.39; p = 0.015 and OR = 4.99; 95% CI = 1.39-17.89; p = 0.014, respectively)., Conclusions: GPi-DBS provides long-term beneficial effects against tremor, motor fluctuation and LID, but PIGD symptoms gradually worsen. This selective long-term benefit has implications for the optimal application of DBS in PD patients., (Copyright © 2022. Published by Elsevier B.V.)

We aimed to investigate the predictive value of preoperative clinical factors and dopamine transporter imaging for outcomes after globus pallidus interna (GPi) deep brain stimulation (DBS) in patients with advanced Parkinson's disease (PD). Thirty-one patients with PD who received bilateral GPi DBS were included. The patients underwent preoperative [ 18 F] FP-CIT positron emission tomography before DBS surgery. The Unified Parkinson's Disease Rating Scale (UPDRS) were used to assess outcomes 12 months after DBS. Univariate and multivariate linear regression analysis were performed to investigate the association between clinical variables including sex, age at onset of PD, disease duration, cognitive status, preoperative motor severity, levodopa responsiveness, daily dose of dopaminergic medication, and dopamine transporter availability in the striatum and outcomes after GPi DBS. Younger age at onset of PD was associated with greater DBS motor responsiveness and lower postoperative UPDRS III score. Greater levodopa responsiveness, lower preoperative UPDRS III score and lower striatal dopamine transporter availability were associated with lower postoperative UPDRS III score. Younger age at onset was also associated with greater decrease in UPDRS IV score and dyskinesia score after GPi DBS. Our results provide useful information to select DBS candidates and predict therapeutic outcomes after GPi DBS in advanced PD., (© 2022. The Author(s).)

Introduction: Deep brain stimulation (DBS) has showed variable therapeutic effect on freezing of gait (FOG) in Parkinson's disease (PD). It is unclear which factors associated with the effect of DBS on FOG in patients with advanced PD. In this study, we investigated the correlation of pre and postoperative factors with the therapeutic effect of globus pallidus interna (GPi) DBS on FOG in PD patients., Methods: We retrospectively analyzed PD patients with FOG (N = 20) who underwent GPi DBS surgery. Postoperatively, video-based analysis for FOG severity was performed at the first DBS programming and patients were categorized into two groups according to DBS effect on FOG (11 FOG responders and 9 FOG non-responders) at medication-off state. We analyzed preoperative clinical characteristics, cognitive function, striatal dopamine transporter availability, postoperative DBS programming parameters, lead locations, and volume of tissue activated in functional subregions of GPi. Bootstrap enhanced Elastic-Net logistic regression was used to select pre and postoperative factors associated with the effect of GPi DBS., Results: Therapeutic effect of GPi DBS on FOG were correlated with the disease duration of PD before DBS surgery, preoperative improvement in FOG severity by levodopa medication, and the distance from active contact of DBS electrode to the prefrontal region of GPi anatomical site., Conclusions: Our study results suggest that the effect of GPi DBS on FOG is correlated with disease duration, levodopa responsiveness on FOG before DBS surgery and DBS electrode location, providing useful information to predict FOG outcome after GPi DBS in PD patients., (Copyright © 2021. Published by Elsevier Ltd.)

Background: Although dementia is a contraindication for deep brain stimulation (DBS) in patients with Parkinson's disease (PD), the concept is supported by little scientific evidence. Moreover, it is unclear whether PD with mild cognitive impairment (PD-MCI) or domain-specific cognitive impairments affect the outcome of DBS in non-demented PD patients., Objective: To investigate the influence of baseline cognitive profiles of PD on the outcome of DBS., Methods: Baseline cognitive levels of patients with PD who underwent DBS were classified into PD with dementia (PDD) (n = 15), PD-MCI (n = 210), and normal cognition (PD-NC) (n = 79). The impact of the cognitive level on key DBS outcome measures [mortality, nursing home admission, progression to Hoehn&Yahr (HY) stage 5 and progression to PDD] were analyzed using Cox regression models. We also investigated whether impairment of a specific cognitive domain could predict these outcomes in non-demented patients., Results: Patients with PDD showed a substantially higher risk of nursing home admission and progression to HY stage 5 compared with patients with PD-MCI [hazard ratio (HR) 4.20, P = .002; HR = 5.29, P < .001] and PD-NC (HR 7.50, P < .001; HR = 7.93, P < .001). MCI did not alter the prognosis in patients without dementia, but those with visuospatial impairment showed poorer outcomes for nursing home admission (P = .015), progression to HY stage 5 (P = .027) and PDD (P = .006)., Conclusions: Cognitive profiles may stratify the pre-operative risk and predict long-term outcomes of DBS in PD., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Brain-derived exosomes circulate in the bloodstream and other bodily fluids, serving as potential indicators of neurological disease progression. These exosomes present a promising avenue for the early and precise diagnosis of neurodegenerative conditions. Notably, miRNAs found in plasma extracellular vesicles (EVs) offer distinct diagnostic benefits due to their stability, abundance, and resistance to breakdown. In this study, we introduce a method using transferrin conjugated magnetic nanoparticles (TMNs) to isolate these exosomes from the plasma of patients with neurological disorders. This TMNs technique is both quick (<35 min) and cost-effective, requiring no high-priced ingredients or elaborate equipment for EV extraction. Our method successfully isolated EVs from 33 human plasma samples, including those from patients with Parkinson's disease (PD), Multiple Sclerosis (MS), and Dementia. Using quantitative polymerase chain reaction (PCR) analysis, we evaluated the potential of 8 exosomal miRNA profiles as biomarker candidates. Six exosomal miRNA biomarkers (miR-195-5p, miR-495-3p, miR-23b-3P, miR-30c-2-3p, miR-323a-3p, and miR-27a-3p) were consistently linked with all stages of PD. The TMNs method provides a practical, cost-efficient way to isolate EVs from biological samples, paving the way for non-invasive neurological diagnoses. Furthermore, the identified miRNA biomarkers in these exosomes may emerge as innovative tools for precise diagnosis in neurological disorders including PD. We introduce a method using transferrin conjugated magnetic nanoparticles (TMNs) to isolate these exosomes from the plasma of patients with neurological disorders. This TMNs technique is both quick (<35 min) and cost-effective, requiring no high-priced ingredients or elaborate equipment for EV extraction, paving the way for non-invasive neurological diagnoses. [Display omitted] • A transferrin conjugated magnetic nanoparticles (TMNs) method to isolate extracellular vesicles including exosomes. • TMNs technique is both quick (<35 min) and cost-effective, requiring no high-priced ingredients or elaborate equipment. • Evaluated the potential of 8 exosomal miRNA profiles as biomarker candidates in Parkinson's diseases. • Identified exosomal miRNA biomarkers may emerge as innovative tools for precise diagnosis in neurological disorders. [ABSTRACT FROM AUTHOR]