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Objectives: To determine the effect of Bilateral Subthalamic Nucleus (STN) Deep Brain Stimulation (DBS) on drug reduction for Parkinson's disease (PD) in a low-middle-income country. Methods: This retrospective cohort study included 49 patients following interview based questionnaires who underwent bilateral STN DBS at the Department of Neurosurgery, Punjab Institute of Neurosciences, Lahore, Pakistan over five years (July 30, 2018 to June 29, 2023). Patients meeting the inclusion and exclusion criteria (49 patients) were selected and the effect of bilateral STN DBS on drug reduction was evaluated. Results: Following bilateral STN for Parkinsons Disease Levodopa equivalent daily dose (LEDD) and Unified Parkinson's Disease Rating Scale (UPDRS)-III results were statistically significant, with a P-value of 0.0001. Effect of DBS on UPDRSIV was 0.2751, which is statistically insignificant. LEDD reduced by 55.03% (P<0.0001), UPRS-III improved by 80.49% (P<0.0001), and UPDRS-IV improved by 1% (P<0.0001). Time spent with dyskinesia reduced by 17.54% (P<0.0001), whereas time spent off period reduced 22.44% (P<0.0001). Conclusion: When the disease is in its early stages and has not yet manifested advanced Parkinsons symptoms, bilateral STN DBS is an effective treatment option. It considerably reduces the need for levodopa and significantly improves the motor symptoms of rigidity, tremors, and bradykinesia. [ABSTRACT FROM AUTHOR]

Abstract Background Parkinson's disease (PD) is the second most prevalent neurodegenerative ailment affecting aged people. Several motor and non-motor symptoms appearing with this disease are linked to reduction in dopamine levels. Parkinson’s disease manifested by a wide range of symptoms, including gait instability, voice impairments, bradykinesia, hypomimia, tremors, and cognitive dysfunctions, where the concern is its steady global progression. Therefore, by evaluating the stage-specific retention and transition thresholds, the suggested work attempts to detect the progression of PD. Similarly, the assessment of the annual rate of deterioration of symptoms aids in assessing the influence of medications on four stages and six prime symptoms. Results During the 9-year period following clinical diagnosis, a symptomatic deterioration of 34.995% is observed in untreated patients compared to treated patients. Furthermore, the experimental analysis illustrates that medicines assist in regulating only bradykinesia, tremors, hypomimia, and speech impairment, which lasts for 4.8 years on average. A saturation period is also identified during the moderate phase, where the computed average depreciation in the Unified Parkinson’s Disease Rating Scale (UPDRS) is the least. Similarly, from stages 1 to 4, medicines might improve stage retention by 4.44, 3.5, 2.72, and 1.6 years, respectively. It demonstrates that, despite transient advantages and adverse effects, medications also have an optimistic impact on PD patients. Conclusions Here, we show that medication can extend the lifespan of PD patients up to 12 years cumulatively. Furthermore, the proposed work suggests that stagewise alternative remedies for improving quality of life, boosting the benefits of medicines, and eliminating their side effects. These include counselling, diet changes, yoga asanas, herbal medicines, bio-cleansing and other therapies. The current work does not consider the temporary transition among stages; nonetheless, further investigation regarding PD could open avenues for more worthy treatments with fewer side effects.

Introduction: People with Parkinson's Disease (PD) often show reduced anticipatory postural adjustments (APAs) before voluntary steps, impacting their stability. The specific subphase within the APA stage contributing significantly to fall risk remains unclear. Methods: We analyzed center of pressure (CoP) trajectory parameters, including duration, length, and velocity, throughout gait initiation. This examination encompassed both the postural phase, referred to as anticipatory postural adjustment (APA) (APA1, APA2a, APA2b), and the subsequent locomotor phases (LOC). Participants were instructed to initiate a step and then stop (initiating a single step). Furthermore, we conducted assessments of clinical disease severity using the Unified Parkinson's Disease Rating Scale (UPDRS) and evaluated fall risk using Tinetti gait and balance scores during off-medication periods. Results: Freezing of gait (FOG) was observed in 18 out of 110 participants during the measurement of CoP trajectories. The Ramer-Douglas-Peucker algorithm successfully identified CoP displacement trajectories in 105 participants (95.5%), while the remaining 5 cases could not be identified due to FOG. Tinetti balance and gait score showed significant associations with levodopa equivalent daily dose, UPDRS total score, disease duration, duration (s) in APA2a (s) and LOC (s), length in APA1 (cm) and APA2b (cm), mediolateral velocity in APA1 (X) (cm/s), APA2a (X) (cm/s), APA2b (X) (cm/s) and LOC (X) (cm/s), and anterior-posterior velocity in APA2a (Z) (cm/s) and APA2b (Z) (cm/s). Multiple linear regression revealed that only duration (s) in APA2a and UPDRS total score was independently associated with Tinetti gait and balance score. Further mediation analysis showed that the duration (s) in APA2a served as a mediator between UPDRS total score and Tinetti balance and gait score (Sobel test, p = 0.047). Conclusion: APA2 subphase duration mediates the link between disease severity and fall risk in PD, suggesting that longer APA2a duration may indicate reduced control during gait initiation, thereby increasing fall risk. [ABSTRACT FROM AUTHOR]

Background: Parkinson's disease (PD) is the second most prevalent neurodegenerative ailment affecting aged people. Several motor and non-motor symptoms appearing with this disease are linked to reduction in dopamine levels. Parkinson's disease manifested by a wide range of symptoms, including gait instability, voice impairments, bradykinesia, hypomimia, tremors, and cognitive dysfunctions, where the concern is its steady global progression. Therefore, by evaluating the stage-specific retention and transition thresholds, the suggested work attempts to detect the progression of PD. Similarly, the assessment of the annual rate of deterioration of symptoms aids in assessing the influence of medications on four stages and six prime symptoms. Results: During the 9-year period following clinical diagnosis, a symptomatic deterioration of 34.995% is observed in untreated patients compared to treated patients. Furthermore, the experimental analysis illustrates that medicines assist in regulating only bradykinesia, tremors, hypomimia, and speech impairment, which lasts for 4.8 years on average. A saturation period is also identified during the moderate phase, where the computed average depreciation in the Unified Parkinson's Disease Rating Scale (UPDRS) is the least. Similarly, from stages 1 to 4, medicines might improve stage retention by 4.44, 3.5, 2.72, and 1.6 years, respectively. It demonstrates that, despite transient advantages and adverse effects, medications also have an optimistic impact on PD patients. Conclusions: Here, we show that medication can extend the lifespan of PD patients up to 12 years cumulatively. Furthermore, the proposed work suggests that stagewise alternative remedies for improving quality of life, boosting the benefits of medicines, and eliminating their side effects. These include counselling, diet changes, yoga asanas, herbal medicines, bio-cleansing and other therapies. The current work does not consider the temporary transition among stages; nonetheless, further investigation regarding PD could open avenues for more worthy treatments with fewer side effects. [ABSTRACT FROM AUTHOR]

Background and Objectives: Currently, no tool exists to predict clinical outcomes in patients with advanced Parkinson's disease (PD) under levodopa–carbidopa intestinal gel (LCIG) treatment. The aim of this study was to develop a novel deep neural network model to predict the clinical outcomes of patients with advanced PD after two years of LCIG therapy. Materials and Methods: This was a longitudinal, 24-month observational study of 59 patients with advanced PD in a multicenter registry under LCIG treatment from September 2019 to September 2021, including 43 movement disorder centers. The data set includes 649 measurements of patients, which make an irregular time series, and they are turned into regular time series during the preprocessing phase. Motor status was assessed with the Unified Parkinson's Disease Rating Scale (UPDRS) Parts III (off) and IV. The NMS was assessed by the NMS Questionnaire (NMSQ) and the Geriatric Depression Scale (GDS), the quality of life by PDQ-39, and severity by Hoehn and Yahr (HY). Multivariate linear regression, ARIMA, SARIMA, and Long Short-Term Memory–Recurrent NeuralNetwork (LSTM-RNN) models were used. Results: LCIG significantly improved dyskinesia duration and quality of life, with men experiencing a 19% and women a 10% greater improvement, respectively. Multivariate linear regression models showed that UPDRS-III decreased by 1.5 and 4.39 units per one-unit increase in the PDQ-39 and UPDRS-IV indexes, respectively. Although the ARIMA-(2,0,2) model is the best one with AIC criterion 101.8 and validation criteria MAE = 0.25, RMSE = 0.59, and RS = 0.49, it failed to predict PD patients' features over a long period of time. Among all the time series models, the LSTM-RNN model predicts these clinical characteristics with the highest accuracy (MAE = 0.057, RMSE = 0.079, RS = 0.0053, mean square error = 0.0069). Conclusions: The LSTM-RNN model predicts, with the highest accuracy, gender-dependent clinical outcomes in patients with advanced PD after two years of LCIG therapy. [ABSTRACT FROM AUTHOR]

Introduction Parkinson's disease represents a burdensome condition with complex manifestations. A licensed, standardized paper-based questionnaire is completed by both patients and physicians to monitor the progression and state of the disease. However, integrating the obtained scores into digital systems still poses a challenge. Methods Paper-based handwriting is intuitive and an efficient mode of human-computer interaction. Accordingly, we transformed a consumer-grade tablet into a device where an exact digital copy of the disease-specific questionnaire can be filled with the supplied pen. Utilizing a small convolutional neural network directly on the device and trained on MNIST data, we translated the handwritten digits to appropriate LOINC codes and made them accessible through a FHIRcompatible HTTP interface. Results When evaluating the usability from a patientcentric point of view, the System Usability Score revealed an excellent rating (SUS = 83.01) from the participants. However, we identified some challenges associated with the magnetic pen and the flat design of the device. Conclusion In setups where certified medical devices are not required, consumer hardware can be used to map handwritten digits of patients to appropriate medical standards without manual intervention through healthcare professionals. [ABSTRACT FROM AUTHOR]

Continuous deep brain stimulation (cDBS) of the subthalamic nucleus (STN) or globus pallidus is an effective treatment for the motor symptoms of Parkinson's disease. The relative benefit of one region over the other is of great interest but cannot usually be compared in the same patient. Simultaneous DBS of both regions may synergistically increase the therapeutic benefit. Continuous DBS is limited by a lack of responsiveness to dynamic, fluctuating symptoms intrinsic to the disease. Adaptive DBS (aDBS) adjusts stimulation in response to biomarkers to improve efficacy, side effects, and efficiency. We combined bilateral DBS of both STN and globus pallidus (dual target DBS) in a prospective within-participant, clinical trial in six patients with Parkinson's disease (n = 6, 55–65 years, n = 2 females). Dual target cDBS was tested for Parkinson's disease symptom control annually over 2 years, measured by motor rating scales, on time without dyskinesia, and medication reduction. Random amplitude experiments probed system dynamics to estimate parameters for aDBS. We then implemented proportional-plus-integral aDBS using a novel distributed (off-implant) architecture. In the home setting, we collected tremor and dyskinesia scores as well as individualized β and DBS amplitudes. Dual target cDBS reduced motor symptoms as measured by Unified Parkinson's Disease Rating Scale (UPDRS) to a greater degree than either region alone (P < 0.05, linear mixed model) in the cohort. The amplitude of β-oscillations in the STN correlated to the speed of hand grasp movements for five of six participants (P < 0.05, Pearson correlation). Random amplitude experiments provided insight into temporal windowing to avoid stimulation artefacts and demonstrated a correlation between STN β amplitude and DBS amplitude. Proportional plus integral control of aDBS reduced average power, while preserving UPDRS III scores in the clinic (P = 0.28, Wilcoxon signed rank), and tremor and dyskinesia scores during blinded testing at home (n = 3 , P > 0.05, Wilcoxon ranked sum). In the home setting, DBS power reductions were slight but significant. Dual target cDBS may offer an improvement in treatment of motor symptoms of Parkinson's disease over DBS of either the STN or globus pallidus alone. When combined with proportional plus integral aDBS, stimulation power may be reduced, while preserving the increased benefit of dual target DBS. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a progressive neurodegenerative disorder. Long non-coding RNA (lncRNA) XIST has been implicated in the development of PD. Herein, we sought to investigate the diagnostic value of serum XIST expression in PD. We recorded clinical baseline data, including age, sex, body mass index (BMI), years of education, and PD family history, for PD patients and healthy controls, in addition to the disease course in PD patients. The disease severity of PD patients was assessed using the Hoehn-Yahr grading scale. We evaluated serum XIST expression levels in PD patients and healthy controls using RT-qPCR and assessed the correlation between serum XIST expression and the Unified Parkinson's Disease Rating Scale (UPDRS) score. Additionally, we used receiver operating characteristic (ROC) curve to determine the diagnostic value of XIST expression for PD. Our results showed no significant differences in age, sex, BMI, and years of education between PD patients and healthy controls. However, more PD patients had a family history of PD. We found that serum XIST expression was significantly up-regulated in PD patients, and its levels were positively correlated with the UPDRS score. Higher PD stage was also associated with increased serum XIST expression. ROC analysis revealed that XIST expression had a diagnostic value for PD. In conclusion, our findings suggest that serum lncRNA XIST expression may serve as a potential diagnostic biomarker for PD. [ABSTRACT FROM AUTHOR]

Introduction: Several studies have reported iron accumulation in the basal ganglia to be associated with the development of Parkinson's Disease (PD). Recently, a few trials have examined the efficacy of using the iron‐chelating agent Deferiprone (DFP) for patients with PD. We conducted this meta‐analysis to summarize and synthesize evidence from published randomized controlled trials about the efficacy of DFP for PD patients. Methods: A comprehensive literature search of four electronic databases was performed, spanning until February 2023. Relevant RCTs were selected, and their data were extracted and analyzed using the RevMan software. The primary outcome was the change in the Unified Parkinson's Disease Rating Scale (UPDRS‐III). Results: Three RCTs with 431 patients were included in this analysis. DFP did not significantly improve UPDRS‐III score compared to placebo (Standardized mean difference −0.06, 95% CI [−0.69, 0.58], low certainty evidence). However, it significantly reduced iron accumulation in the substantia nigra, putamen, and caudate as measured by T2*‐weighted MRI (with high certainty evidence). Conclusion: Current evidence does not support the use of DFP in PD patients. Future disease‐modification trials with better population selection, adjustment for concomitant medications, and long‐term follow up are recommended. [ABSTRACT FROM AUTHOR]

Abstract Background Parkinson’s disease (PD) is distinguished recently by an increase in inflammation and oxidative stress. Apolipoprotein D (Apo D) is a neuroprotective protein that was discovered to be increased in PD-affected brains. The aim of our study was to measure the ApoD serum level in individuals with PD and to correlate it with the clinical data of those individuals. Thirty individuals suffering from idiopathic PD were subjected to neurological examination, disease intensity by applying the Unified Parkinson’s Disease Rating Scale (UPDRS) and measurement of Apo D blood levels. Thirty age and sex matched controls were included for comparison of Apo D concentration. Results Apolipoprotein D levels were substantially greater in PD individuals than in controls. The correlation between Apo D serum level and PD severity determined by the UPDRS and its subscales was positive. Conclusion PD patients had increased blood level concentration of Apo D, which was associated positively with disease intensity. We suggest that Apo D serum level can be used as a predictor factor for PD severity. More studies are warranted to study how to target the Apo D in PD patients and thus helping to reduce the oxidative stress and inflammatory cascade involved in the pathogenesis of the disease.

BackgroundIncreasing evidence connects the gut microbiome to Parkinson's disease (PD) etiology, but little is known about microbial contributions to PD progression and its clinical features.ObjectiveWe aim to explore the association between the gut microbiome with PD, and the microbial association with PD-specific clinical features.MethodsIn a community-based case-control study of 96 PD patients and 74 controls, microbiome data were obtained from 16S rRNA gene sequencing of fecal samples, and analyzed for microbial diversity, taxa abundance, and predicted functional pathways that differed in PD patients and controls, and their association with PD-specific features (disease duration, motor subtypes, L-DOPA daily dose, and motor function).ResultsPD patients' gut microbiome showed lower species diversity (p = 0.04) and were compositionally different (p = 0.002) compared to controls but had a higher abundance of three phyla (Proteobacteria, Verrucomicrobiota, Actinobacteria) and five genera (Akkermansia, Enterococcus, Hungatella, and two Ruminococcaceae) controlling for sex, race, age, and sequencing platform. Also, 35 Metacyc pathways were predicted to be differentially expressed in PD patients including biosynthesis, compound degradation/utilization/assimilation, generation of metabolites and energy, and glycan pathways. Additionally, the postural instability gait dysfunction subtype was associated with three phyla and the NAD biosynthesis pathway. PD duration was associated with the Synergistota phylum, six genera, and the aromatic compound degradation pathways. Two genera were associated with motor function.ConclusionPD patients differed from controls in gut microbiome composition and its predicted metagenome. Clinical features were also associated with bacterial taxa and altered metabolic pathways of interest for PD progression.

目的 运用网状meta分析探讨血管性帕金森综合征（vascular parkinsonism，VP）药物治疗的疗效及安全性。 方法 计算机检索中国知网、万方数据知识服务平台、维普中文期刊服务平台、PubMed、Web of Science、MEDLINE、Embase、Cochrane Library收录的VP药物治疗的随机对照试验，检索时限为各数据库建库至2023年1月1日。由两名研究员独立进行文献筛选、数据提取并对纳入的研究进行质量评价，应用R软件对数据进行网状meta分析。 结果 最终纳入20项研究，包括丁苯酞联合多巴丝肼、依达拉奉联合多巴丝肼、盐酸普拉克索联合多巴丝肼、单用多巴丝肼4种药物疗法。总体文献质量水平中等。网状meta分析结果显示：①在治疗总有效率方面，优选概率排名曲线（surface under the cumulative ranking curve，SUCRA）排序结果显示，丁苯酞联合多巴丝肼＞依达拉奉联合多巴丝肼＞盐酸普拉克索联合多巴丝肼＞单用多巴丝肼；②在帕金森病统一评分量表（unified Parkinson’s disease rating scale，UPDRS）评分改善方面，SUCRA排序结果显示，丁苯酞联合多巴丝肼＞依达拉奉联合多巴丝肼＞盐酸普拉克索联合多巴丝肼＞单用多巴丝肼；③在不良反应方面，SUCRA排序结果显示，丁苯酞联合多巴丝肼＞单用多巴丝肼＞盐酸普拉克索联合多巴丝肼＞依达拉奉联合多巴丝肼。 结论 丁苯酞联合多巴丝肼治疗VP的有效率最高，对UPDRS评分改善最明显，且安全性最好，未观察到有明显增加不良反应的风险。但纳入的研究方法学质量普遍偏低，故结论仍待更多大样本、高质量的研究进一步验证。 Abstract: Objective To assess the efficacy and safety of drug treatment of vascular parkinsonism (VP) using network meta-analysis. Methods A computerized search of randomized controlled trials of VP drug treatment in CNKI, Wanfang, VIP, PubMed, Web of Science, MEDLINE, Embase, and Cochrane Library was conducted from the inception each database to January 1, 2023. Two researchers independently performed literature screening, data extraction, and quality evaluation of the included studies. R was applied to perform a network meta-analysis of the data. Results Twenty studies were included, including butylphthalide in combination with levodopa, edaravone in combination with levodopa, pramipexole dihydrochloride in combination with levodopa and levodopa alone. The overall literature quality level is medium. The results of the network meta-analysis showed that: (1) in terms of total treatment effectiveness, the surface under the cumulative ranking curve (SUCRA) showed that butylphthalide in combination with levodopa > edaravone in combination with levodopa > pramipexole dihydrochloride in combination with levodopa > levodopa alone. (2) In terms of unified Parkinson's disease rating scale (UPDRS) scores, the SUCRA showed that butylphthalide in combination with levodopa > edaravone in combination with levodopa > pramipexole dihydrochloride in combination with levodopa > levodopa alone. (3) In terms of adverse reactions, the SUCRA showed that butylphthalide in combination with levodopa > levodopa alone > pramipexole dihydrochloride in combination with levodopa > edaravone in combination with levodopa. Conclusions Butylphthalide in combination with levodopa had the highest efficiency, the most significant improvement in UPDRS scores, and the best safety profile for the treatment of VP, and no significant increased risk of adverse effects was observed. However, the methodological quality of the included studies was generally low, so the conclusions remain to be further validated by studies with larger samples and high quality.

Background Parkinson's disease (PD) is distinguished recently by an increase in inflammation and oxidative stress. Apolipoprotein D (Apo D) is a neuroprotective protein that was discovered to be increased in PD-affected brains. The aim of our study was to measure the ApoD serum level in individuals with PD and to correlate it with the clinical data of those individuals. Thirty individuals suffering from idiopathic PD were subjected to neurological examination, disease intensity by applying the Unified Parkinson's Disease Rating Scale (UPDRS) and measurement of Apo D blood levels. Thirty age and sex matched controls were included for comparison of Apo D concentration. Results Apolipoprotein D levels were substantially greater in PD individuals than in controls. The correlation between Apo D serum level and PD severity determined by the UPDRS and its subscales was positive. Conclusion PD patients had increased blood level concentration of Apo D, which was associated positively with disease intensity. We suggest that Apo D serum level can be used as a predictor factor for PD severity. More studies are warranted to study how to target the Apo D in PD patients and thus helping to reduce the oxidative stress and inflammatory cascade involved in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Abstract Background The clinical utility and safety of sargramostim has previously been reported in cancer, acute radiation syndrome, autoimmune disease, inflammatory conditions, and Alzheimer’s disease. The safety, tolerability, and mechanisms of action in Parkinson’s disease (PD) during extended use has not been evaluated. Methods As a primary goal, safety and tolerability was assessed in five PD patients treated with sargramostim (Leukine®, granulocyte–macrophage colony-stimulating factor) for 33 months. Secondary goals included numbers of CD4+ T cells and monocytes and motor functions. Hematologic, metabolic, immune, and neurological evaluations were assessed during a 5-day on, 2-day off therapeutic regimen given at 3 μg/kg. After 2 years, drug use was discontinued for 3 months. This was then followed by an additional 6 months of treatment. Results Sargramostim-associated adverse events included injection-site reactions, elevated total white cell counts, and bone pain. On drug, blood analyses and metabolic panels revealed no untoward side effects linked to long-term treatment. Unified Parkinson’s Disease Rating Scale scores remained stable throughout the study while regulatory T cell number and function were increased. In the initial 6 months of treatment, transcriptomic and proteomic monocyte tests demonstrated autophagy and sirtuin signaling. This finding paralleled anti-inflammatory and antioxidant activities within both the adaptive and innate immune profile arms. Conclusions Taken together, the data affirmed long-term safety as well as immune and anti-inflammatory responses reflecting clinical stability in PD under the sargramostim treatment. Confirmation in larger patient populations is planned in a future phase II evaluation. Trial registration: ClinicalTrials.gov: NCT03790670, Date of Registration: 01/02/2019, URL: https://clinicaltrials.gov/ct2/show/NCT03790670?cond=leukine+parkinson%27s&draw=2&rank=2 .

Background and Objectives: Currently, no tool exists to predict clinical outcomes in patients with advanced Parkinson’s disease (PD) under levodopa–carbidopa intestinal gel (LCIG) treatment. The aim of this study was to develop a novel deep neural network model to predict the clinical outcomes of patients with advanced PD after two years of LCIG therapy. Materials and Methods: This was a longitudinal, 24-month observational study of 59 patients with advanced PD in a multicenter registry under LCIG treatment from September 2019 to September 2021, including 43 movement disorder centers. The data set includes 649 measurements of patients, which make an irregular time series, and they are turned into regular time series during the preprocessing phase. Motor status was assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS) Parts III (off) and IV. The NMS was assessed by the NMS Questionnaire (NMSQ) and the Geriatric Depression Scale (GDS), the quality of life by PDQ-39, and severity by Hoehn and Yahr (HY). Multivariate linear regression, ARIMA, SARIMA, and Long Short-Term Memory–Recurrent NeuralNetwork (LSTM-RNN) models were used. Results: LCIG significantly improved dyskinesia duration and quality of life, with men experiencing a 19% and women a 10% greater improvement, respectively. Multivariate linear regression models showed that UPDRS-III decreased by 1.5 and 4.39 units per one-unit increase in the PDQ-39 and UPDRS-IV indexes, respectively. Although the ARIMA-(2,0,2) model is the best one with AIC criterion 101.8 and validation criteria MAE = 0.25, RMSE = 0.59, and RS = 0.49, it failed to predict PD patients’ features over a long period of time. Among all the time series models, the LSTM-RNN model predicts these clinical characteristics with the highest accuracy (MAE = 0.057, RMSE = 0.079, RS = 0.0053, mean square error = 0.0069). Conclusions: The LSTM-RNN model predicts, with the highest accuracy, gender-dependent clinical outcomes in patients with advanced PD after two years of LCIG therapy.

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Introduction. According to many reports, multidisciplinary comprehensive care alleviates Parkinson's disease (PD) more frequently than any other standard care, though the results were found to vary greatly. Materials and methods. A systematic literature search up to July 2022 was performed and 1234 related studies were evaluated. The chosen studies comprised 1115 subjects with PD who participated in baseline trials; 633 of them were under multidisciplinary comprehensive care, while 482 were under standard care. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (95% CIs) were calculated to measure the results of multidisciplinary comprehensive care for PD by the contentious and dichotomous approaches with a random or fixed influence model employed. Results. The use of multidisciplinary comprehensive care resulted in significantly better health-related quality of life (HRQL) (MD: -3.17; 95% CI: -5.98--0.35, p = 0.03) and Unified Parkinson's Disease Rating Scale (UPDRS) score (MD: -5.25; 95% CI: -10.14--0.37, p = 0.04) compared to the standard care for subjects with PD. Nevertheless, no significant difference was found between multidisciplinary comprehensive care and standard care for subjects with PD regarding medication dosage (MD: 0.31; 95% CI: -0.72-1.34, p = 0.56) and caregiver strain (MD: -0.51; 95% CI: -1.69-0.67, p = 0.40). Conclusions. Outpatient multidisciplinary comprehensive care models may improve patient-reported HRQL and UPDRS score; nevertheless, no significant difference was found in terms of medication dosage and care-giver strain compared to the standard care for subjects with PD. The small sample size of 2 out of 7 analyzed studies and the small number of studies in certain comparisons requires attention when analyzing the results. [ABSTRACT FROM AUTHOR]

Background: The clinical utility and safety of sargramostim has previously been reported in cancer, acute radiation syndrome, autoimmune disease, inflammatory conditions, and Alzheimer's disease. The safety, tolerability, and mechanisms of action in Parkinson's disease (PD) during extended use has not been evaluated. Methods: As a primary goal, safety and tolerability was assessed in five PD patients treated with sargramostim (Leukine®, granulocyte–macrophage colony-stimulating factor) for 33 months. Secondary goals included numbers of CD4+ T cells and monocytes and motor functions. Hematologic, metabolic, immune, and neurological evaluations were assessed during a 5-day on, 2-day off therapeutic regimen given at 3 μg/kg. After 2 years, drug use was discontinued for 3 months. This was then followed by an additional 6 months of treatment. Results: Sargramostim-associated adverse events included injection-site reactions, elevated total white cell counts, and bone pain. On drug, blood analyses and metabolic panels revealed no untoward side effects linked to long-term treatment. Unified Parkinson's Disease Rating Scale scores remained stable throughout the study while regulatory T cell number and function were increased. In the initial 6 months of treatment, transcriptomic and proteomic monocyte tests demonstrated autophagy and sirtuin signaling. This finding paralleled anti-inflammatory and antioxidant activities within both the adaptive and innate immune profile arms. Conclusions: Taken together, the data affirmed long-term safety as well as immune and anti-inflammatory responses reflecting clinical stability in PD under the sargramostim treatment. Confirmation in larger patient populations is planned in a future phase II evaluation. Trial registration: ClinicalTrials.gov: NCT03790670, Date of Registration: 01/02/2019, URL:https://clinicaltrials.gov/ct2/show/NCT03790670?cond=leukine+parkinson%27s&draw=2&rank=2. [ABSTRACT FROM AUTHOR]

Introduction: Parkinson’s disease (PD) is characterized by an alteration of the walking gait, frequently including a slower self-selected walking speed (SSWS). Although the reduction of walking speed is inherent to people with PD, such speed reduction also represents a potential confounding factor that might partly explain the observed gait differences between PD and control participants. Methods: In this study, each participant walked along a 25 m level corridor during which vertical ground reaction force signals were recorded using shoes equipped with eight pressure sensors. Vertical ground reaction force signals (using statistical parametric mapping) and temporal and kinetic variables as well as their related variability and asymmetry (using Student’s t-test) were compared between PD (n = 54) and walking-speed-matched control subjects (n = 39). Results: Statistical parametric mapping did not yield significant differences between PD and control groups for the vertical ground reaction force signal along the walking stance phase. Stride time and single support time (equivalent to swing time) were shorter and peak vertical ground reaction force was larger in PD patients compared to controls (p≤ 0.05). However, the single support time was no longer different between people with PD and healthy subjects when expressed relatively to stride time (p = 0.07). While single support, double support, and stance times were significantly more variable and asymmetric for PD than for the control group (p≤ 0.05), stride time was similar (p≥ 0.07). Discussion: These results indicate that at matched SSWS, PD patients adopt a higher cadence than control participants. Moreover, the temporal subdivision of the walking gait of people with PD is similar to healthy individuals but the coordination during the double support phase is different. Hence, this study indicates that isolating the speed factor is crucial in gait analysis for PD. [ABSTRACT FROM AUTHOR]

We sought to design a data visualization platform to represent the Movement Disorder Society- Unified Parkinson's Disease Rating Scale (MDS-UPDRS) item scores in an easy-to-use display without modification of the raw data or summary scores. Score items for Parts I, II, and IV were arranged as separate inline blocks, while Part III item blocks were arranged in an anatomical fashion. A color scale was created to represent symptom severity and changes observed from one exam to another. We have found the visualization helpful for quickly defining the most troublesome symptoms and their anatomical location enabling communication of the results and interpretations. [ABSTRACT FROM AUTHOR]

The authors examined the associations between the performance of upper- and lower-extremity motor tasks across task complexity and motor symptom severity, overall disease severity, and the physical aspects of quality of life in persons with Parkinson's disease. The performance was assessed for three lower-extremity tasks and two upper-extremity tasks of different levels of complexity. The motor symptoms and overall disease severity correlated significantly with all motor tasks with higher correlation coefficients in the complex tasks. Thus, the strength of the association between disease severity or severity of motor symptoms and motor performance is task-specific, with higher values in complex motor tasks than in simpler motor tasks. Mobility-related and activity-of-daily-living-related quality of life correlated with lower-extremity tasks of low and medium complexity and with the complex upper-extremity task, respectively; this suggests that Parkinson's Disease Questionnaire-39 is capable of differentiating between the impact of gross and fine motor function on quality of life. [ABSTRACT FROM AUTHOR]

Background: Drug efficacy generally varies with different durations. There is no systematic review analyzing the effect of selegiline for Parkinson's disease (PD) on different treatment duration. This study aims to analyze how the efficacy and safety of selegiline changes for PD over time. Methods: PubMed, the Cochrane Library, Embase, China National Knowledge Infrastructure and Wanfang Database were systematically retrieved for randomized controlled trials (RCTs) and observational studies of selegiline for PD. The search period was from inception to January 18th, 2022. The efficacy outcomes were measured by the mean change from baseline in the total and sub Unified Parkinson's Disease Rating Scale (UPDRS), Hamilton Depression Rating Scale (HAMD) and Webster Rating Scale (WRS) scores. The safety outcomes were measured by the proportion of participants having any adverse events overall and that in different system organ classes. Results: Among the 3,786 studies obtained, 27 RCTs and 11 observational studies met the inclusion criteria. Twenty-three studies reported an outcome which was also reported in at least one other study, and were included in meta-analyses. Compared with placebo, selegiline was found with a stronger reduction of total UPDRS score with increasing treatment duration [mean difference and 95% CIs in 1 month: -3.56 (-6.67, -0.45); 3 months: -3.32 (-3.75, -2.89); 6 months: -7.46 (-12.60, -2.32); 12 months: -5.07 (-6.74, -3.41); 48 months: -8.78 (-13.75, -3.80); 60 months: -11.06 (-16.19, -5.94)]. A similar trend was also found fromthe point estimates in UPDRS I, II, III, HAMD andWRS score. The results of observational studies on efficacy were not entirely consistent. As for safety, compared with placebo, selegiline had higher risk of incurring any adverse events [rate: 54.7% vs. 62.1%; odd ratio and 95% CIs: 1.58 (1.02, 2.44)], with the excess adverse events mainly manifested as neuropsychiatric disorders [26.7% vs. 31.6%; 1.36 (1.06, 1.75)] and no significant change over time. The statistically difference in overall adverse event between selegiline and active controls was not found. Conclusion: Selegiline was effective in improving total UPDRS score with increasing treatment duration, and had a higher risk of incurring adverse events, especially the adverse events in the neuropsychiatric system. [ABSTRACT FROM AUTHOR]

The rehabilitation evaluation of Parkinson's disease has always been the research focus of human assistive systems. It is a research hotspot to objectively and accurately evaluate the gait condition of Parkinson's disease patients, thereby adjusting the actuators of the human–machine system and making rehabilitation robots better adapt to the recovery process of patients. The rehabilitation evaluation of Parkinson's disease has always been the research focus of rehabilitation robots. It is a research hotspot to be able to objectively and accurately evaluate the recovery of Parkinson's disease patients, thereby adjusting the driving module of the human–machine collaboration system in real time, so that rehabilitation robots can better adapt to the recovery process of Parkinson's disease. The gait task in the Unified Parkinson's Disease Rating Scale (UPDRS) is a widely accepted standard for assessing the gait impairments of patients with Parkinson's disease (PD). However, the assessments conducted by neurologists are always subjective and inaccurate, and the results are determined by the neurologists' observation and clinical experience. Thus, in this study, we proposed a novel machine learning-based method of automatically assessing the gait task in UPDRS with wearable sensors as a more convenient and objective alternative means for PD gait assessment. In the design, twelve gait features, including three spatial–temporal features and nine kinematic features, were extracted and calculated from two shank-mounted IMUs. A novel nonlinear model is developed for calculating the score of gait task from the gait features. Twenty-five PD patients and twenty-eight healthy subjects were recruited for validating the proposed method. For comparison purpose, three traditional models, which have been used in previous studies, were also tested by the same dataset. In terms of percentages of participants, 84.9%, 73.6%, 73.6%, and 66.0% of the participants were accurately assigned into the true level with the proposed nonlinear model, the support vector machine model, the naive Bayes model, and the linear regression model, respectively, which indicates that the proposed method has a good performance on calculating the score of the UPDRS gait task and conformance with the rating done by neurologists. [ABSTRACT FROM AUTHOR]

IntroductionParkinson’s disease (PD) is characterized by an alteration of the walking gait, frequently including a slower self-selected walking speed (SSWS). Although the reduction of walking speed is inherent to people with PD, such speed reduction also represents a potential confounding factor that might partly explain the observed gait differences between PD and control participants.MethodsIn this study, each participant walked along a 25 m level corridor during which vertical ground reaction force signals were recorded using shoes equipped with eight pressure sensors. Vertical ground reaction force signals (using statistical parametric mapping) and temporal and kinetic variables as well as their related variability and asymmetry (using Student’s t-test) were compared between PD (n = 54) and walking-speed-matched control subjects (n = 39).ResultsStatistical parametric mapping did not yield significant differences between PD and control groups for the vertical ground reaction force signal along the walking stance phase. Stride time and single support time (equivalent to swing time) were shorter and peak vertical ground reaction force was larger in PD patients compared to controls (p ≤ 0.05). However, the single support time was no longer different between people with PD and healthy subjects when expressed relatively to stride time (p = 0.07). While single support, double support, and stance times were significantly more variable and asymmetric for PD than for the control group (p ≤ 0.05), stride time was similar (p ≥ 0.07).DiscussionThese results indicate that at matched SSWS, PD patients adopt a higher cadence than control participants. Moreover, the temporal subdivision of the walking gait of people with PD is similar to healthy individuals but the coordination during the double support phase is different. Hence, this study indicates that isolating the speed factor is crucial in gait analysis for PD.

Background: Assessment of motor signs in Parkinson's disease (PD) requires an in-person examination. However, 50% of people with PD do not have access to a neurologist. Wearable sensors can provide remote measures of some motor signs but require continuous monitoring for several days. A major unmet need is reliable metrics of all cardinal motor signs, including rigidity, from a simple short active task that can be performed remotely or in the clinic. Objective: Investigate whether thirty seconds of repetitive alternating finger tapping (RAFT) on a portable quantitative digitography (QDG) device, which measures amplitude and timing, produces reliable metrics of all cardinal motor signs in PD. Methods: Ninety-six individuals with PD and forty-two healthy controls performed a thirty-second QDG-RAFT task and clinical motor assessment. Eighteen individuals were followed longitudinally with repeated assessments for an average of three years and up to six years. Results: QDG-RAFT metrics showed differences between PD and controls and provided correlated metrics for total motor disability (MDS-UPDRS III) and for rigidity, bradykinesia, tremor, gait impairment, and freezing of gait (FOG). Additionally, QDG-RAFT tracked disease progression over several years off therapy and showed differences between akinetic-rigid and tremor-dominant phenotypes, as well as people with and without FOG. Conclusions: QDG is a reliable technology, which could be used in the clinic or remotely. This could improve access to care, allow complex remote disease management based on data received in real time, and accurate monitoring of disease progression over time in PD. QDG-RAFT also provides the comprehensive motor metrics needed for therapeutic trials. [ABSTRACT FROM AUTHOR]

Background: Freezing of gait (FOG) is among the most common and disabling symptoms of Parkinson's disease (PD). Studies show that deep brain stimulation (DBS) of the subthalamic nucleus (STN) can reduce FOG severity. However, there is uncertainty about pathways that need to be modulated to improve FOG. Objective: To investigate whether STN-DBS effectively reduces FOG postoperatively and whether structural connectivity of the stimulated tissue explains variance of outcomes. Methods: We investigated 47 patients with PD and preoperative FOG. Freezing prevalence and severity was primarily assessed using the Freezing of Gait Questionnaire (FOG-Q). In a subset of 18 patients, provoked FOG during a standardized walking course was assessed. Using a publicly available model of basal-ganglia pathways we determined stimulation-dependent connectivity associated with postoperative changes in FOG. A region-of-interest analysis to a priori defined mesencephalic regions was performed using a disease-specific normative connectome. Results: Freezing of gait significantly improved six months postoperatively, marked by reduced frequency and duration of freezing episodes. Optimal stimulation volumes for improving FOG structurally connected to motor areas, the prefrontal cortex and to the globus pallidus. Stimulation of the lenticular fasciculus was associated with worsening of FOG. This connectivity profile was robust in a leave-one-out cross-validation. Subcortically, stimulation of fibers crossing the pedunculopontine nucleus and the substantia nigra correlated with postoperative improvement. Conclusion: STN-DBS can alleviate FOG severity by modulating specific pathways structurally connected to prefrontal and motor cortices. More differentiated FOG assessments may allow to differentiate pathways for specific FOG subtypes in the future. [ABSTRACT FROM AUTHOR]

BackgroundVisual Hallucinations (VH) are a common symptom experienced by individuals with Parkinson's disease (PD); however, a validated measure of VH has yet to be established for this population. The North-East Visual Hallucinations Interview (NEVHI), a promising VH measure, has not been well validated in PD. The aim of this study was to evaluate the convergent and discriminant validity of the NEVHI as well as the proportional identification and characteristics of VH in PD.MethodsOne hundred seventeen individuals with PD completed the NEVHI as well as evaluations of psychological, cognitive, motor, and visual functioning as measures of convergent and divergent validity. The hallucination items from the Neuropsychiatric Inventory (NPI) and the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Scale (MDS-UPDRS) were used to assess convergent validity.ResultsThe NEVHI identified 20.5% of PD patients with VH, which consisted of all individuals detected by the MDS-UPDRS and NPI and nine additional individuals not detected by the other measures. The NEVHI was strongly correlated with the MDS-UPDRS hallucinations item, and weakly correlated with the NPI VH item. Weak to non-significant correlations were found between the NEVHI and measures of psychological, cognitive, motor, visual, and demographic characteristics.DiscussionThe NEVHI identified a greater number of individuals with VH than either the MDS-UPDRS or NPI. Results demonstrated good convergent validity between the NEVHI and a clinician-administered-to-patient-report measure of VH and excellent divergent validity, supporting the NEVHI as a valid and preferable measure for assessing the presence of VH in PD.

Purpose of the Study: Sleep problems are frequently encountered in Parkinson's disease (PD), including sleep fragmentation, rapid eye movement (REM) sleep behavior disorder (RBD), excessive daytime sleepiness, and sleep-disordered breathing. In this study, we aimed to examine the relationship between sleep structure and sleep disorders on motor and nonmotor symptoms of PD. Basic Procedures: Seventy-three consecutive patients diagnosed as having PD based on the United Kingdom Brain Bank Criteria were prospectively enrolled. Detailed histories of PD-related symptoms, sleep anamnesis, subjective evaluation of nocturnal sleep, and daytime sleepiness were made. All participants underwent one-night video-polysomnography (PSG) and multiple sleep latency test (MSLT) in a sleep laboratory. Main Findings: A significant correlation was present between female sex and RLS (P = 0.009). Age and body mass index showed no significant correlations with PD-related parameters including Unified Parkinson's Disease Rating Scale (UPDRS) scores and PSG parameters. RLS or RBD showed no significant correlation with PD-related variables. Among PSG parameters, higher REM sleep percentages showed a statistically significant correlation with increased scores of UPDRS part III (P = 0.007). A statistically significant negative correlation was present between apnea–hypopnea index and PD duration (P = 0.005), and the presence of obstructive sleep apnea syndrome (OSAS) was statistically significantly correlated with lower scores of UPDRS part II (P = 0.050). The mean sleep latency in MSLT decreased as the dose of dopaminergic treatment increased (P = 0.016). Principal Conclusions: Our study demonstrated that changes in sleep structure and sleep-related disorders observed in PD could be attributed to intrinsic disease-related properties. The presence of changes in sleep structure as higher REM sleep percentages and sleep-related disorders such as OSAS show correlations with the severity of PD.

Objective: To determine the effects of walking meditation (WM) on functional performance, disease severity, and anxiety in Parkinson's disease (PD). Design: This was a randomized controlled trial. Settings: The study was conducted at a regional hospital. Subjects/Interventions: Thirty-three participants with PD were randomly allocated to the control (CON) group (n = 16) or the WM group (n = 17). Participants in the WM group were asked to perform WM monthly under supervision and encouraged to practice at home at least 3 days/week for 12 weeks. Outcome measurements: Gait velocity, Timed Up and Go, five times sit to stand (FTSTS) test, Unified Parkinson's Disease Rating Scale (UPDRS), and the percentage of participants with anxiety (Hospital Anxiety and Depression Scale-part anxiety [HADS-A] ≥8). Results: Both groups showed reduced gait velocity (p < 0.05), although impairment of the FTSTS (p < 0.05) score was observed only in the CON group. A significant enhancement within and between groups in the total UPDRS and UPDRS part II scores was observed only in the WM group. The percentage of participants with anxiety (HADS-A ≥ 8) decreased significantly only in the WM group (p < 0.05), compared with the baseline and after 12 weeks. There was no loss to follow-up in the WM group, and the participation rate of training was 3.2 days/week. Conclusions: Home-based WM can encourage high rates of exercise adherence, reduce disease severity, lower the percentage of participants with anxiety, and might be suitable during disease endemic and/or pandemic in PD. The protocol was registered on Thaiclinicaltrials.org (Identifier: TCTR20201009001). [ABSTRACT FROM AUTHOR]

Abstract Background Depression and anxiety are non-motor symptoms of Parkinson’s disease (PD) that are often overlooked and underrated. This study aimed to highlight the frequency and risk factors of depression and anxiety among subjects with PD. Methods Sixty-four patients with PD who were diagnosed according to United Kingdom Parkinson’s Disease Society (UKPDS) Brain Bank Criteria and 50 sex- and age-matched healthy control subjects are evaluated for depression and anxiety. PD severity and staging were assessed using Unified Parkinson’s Disease Rating Scale (UPDRS) and Hoehn and Yahr scale. Depression and anxiety were diagnosed using DSM-IV TR criteria and scored using Hamilton Depression and Hamilton Anxiety Rating Scales (HAM-D and HAM-A). The World Health Organization Quality of Life (WHOQOL)-BREF was used to assess impact of depression and anxiety on quality of life. Results 31.25% of patients with PD had depression while 40.6% of patients had anxiety disorder. Depression was higher in females and patients with history of depression and low socioeconomic status (SES). Anxiety was common in young patients and those who had history of anxiety. Overlap between depression and anxiety was recorded in 23.4%. Total UPDRS and Hoehn and Yahr scale accounted for 33.4% of variance for depression. Total UPDRS and earlier age of onset accounted for 39% of variance for anxiety. Advanced disease stage and severity were independent predictors for depression while disease severity and younger age of onset were the main predictors for anxiety. Depression and anxiety have a negative impact on the overall quality of life of PD patients especially on physical and psychosocial domains. Conclusion Depression and anxiety are relatively common in PD. Female gender, low SES, and history of depression were the main risk factors for developing depression. Young age and history of anxiety were risk factors for anxiety. Both had negative impact on quality of life.

Background: Plasma biomarker assays provide an opportunity to reassess whether Alzheimer's disease, Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB) plasma biomarkers are diagnostically useful., Objective: We hypothesized that immunomagnetic reduction (IMR) of plasma biomarkers could differentiate between patients with PDD and DLB and healthy patients when combined with established clinical testing measures., Methods: Plasma samples from 61 participants (12 PDD, 12 DLB, 37 controls) were analyzed using IMR to quantify amyloid-β 42 (Aβ 42 ), total tau (t-tau), phosphorylated tau at threonine 181 (p-tau181), and α-synuclein (α-syn). Receiver operating characteristic curve (ROC) analysis was used to obtain sensitivity, specificity, and area under the ROC curve. Biomarker results were combined with clinical measures from the Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment, and Hoehn-Yahr stage to optimize diagnostic test performance., Results: Participants with PDD had higher α-syn than those with DLB and healthy participants and were distinguishable by their biomarker products Aβ 42 ×p-tau181 and Aβ 42 ×α-syn. Patients with DLB had higher p-tau181 than those with PDD and healthy participants and were distinguishable by their concentrations of α-syn×p-tau181. Plasma α-syn plus UPDRS versus either test alone increased sensitivity, specificity, and AUC when healthy patients were compared with those with PDD and DLB. Combined clinical examination scores and plasma biomarker products demonstrated utility in differentiating PDD from DLB when p-tau181 was combined with UPDRS, α-syn was combined with UPDRS, and α-syn×p-tau181 was combined with UPDRS., Conclusions: In this pilot study, IMR plasma p-tau181 and α-syn may discriminate between PDD and DLB when used in conjunction with clinical testing., Competing Interests: Dr. Malaty declares no conflict of interest at the time this publication was written. Dr. Decourt declares no conflict of interest at the time this publication was written. Dr. Shill received research support from NIH, the Michael J. Fox Foundation for Parkinson’s Research, Transposon Therapeutics, Inc, Saccadous, Inc, the National Institute of Neurological Disorders and Stroke at NIH, Jazz Pharmaceuticals, Inc, Supernus Pharmaceuticals, Inc, The Parkinson’s Foundation, and Barrow Neurological Foundation, and also received consulting honoraria from AbbVie, Inc, and the Tremor Research Group. Dr. Sabbagh discloses ownership interest (stock or stock options) in uMETHOD, Athira Pharma, Inc, CervoMed, Inc, and Lighthouse Pharmaceuticals, Inc; consulting for Alzheon, Inc, Genentech (Roche Group), Prothena Corp, plc, Eisai Co, Ltd, Eli Lilly and Co, Cognito Therapeutics, Inc, and Anavex Life Sciences Corp. Dr. Sabbagh is an Editorial Board member of this journal, but was not involved in the peer-review process of this article nor had access to any information regarding its peer review. An overview of key findings from this study was previously presented in a poster titled “Assessment of Plasma Biomarkers by ImmunoMagnetic Reduction in Parkinson’s Disease Dementia and Dementia with Lewy Bodies” (P10.008) at the American Academy of Neurology meeting held on April 25-26, 2023, in Boston, MA., (© 2024 – The authors. Published by IOS Press.)

Introduction: Parkinson's disease represents a burdensome condition with complex manifestations. A licensed, standardized paper-based questionnaire is completed by both patients and physicians to monitor the progression and state of the disease. However, integrating the obtained scores into digital systems still poses a challenge., Methods: Paper-based handwriting is intuitive and an efficient mode of human-computer interaction. Accordingly, we transformed a consumer-grade tablet into a device where an exact digital copy of the disease-specific questionnaire can be filled with the supplied pen. Utilizing a small convolutional neural network directly on the device and trained on MNIST data, we translated the handwritten digits to appropriate LOINC codes and made them accessible through a FHIR-compatible HTTP interface., Results: When evaluating the usability from a patient-centric point of view, the System Usability Score revealed an excellent rating (SUS = 83.01) from the participants. However, we identified some challenges associated with the magnetic pen and the flat design of the device., Conclusion: In setups where certified medical devices are not required, consumer hardware can be used to map handwritten digits of patients to appropriate medical standards without manual intervention through healthcare professionals.

Studies have shown the spatial specificity of cranial iron deposition in different regions in Parkinson's disease (PD). However, the time-specific patterns of iron deposition are not yet clear. The purpose of this study was to investigate the time pattern of iron variations and its clinical relevance in multiple gray matter nuclei in PD using quantitative susceptibility mapping (QSM). Thirty controls and 33 PD patients were enrolled, namely, 11 cases of early stage of PD (ESP) and 22 cases of advanced stage of PD (ASP) according to the Hoehn-Yahr stages. The iron content in the subcortical nuclei covering substantia nigra (SN), red nucleus (RN), head of the caudate nucleus (CN), globus pallidus (GP), and putamen (PT) was measured using QSM, and the clinical symptoms of PD were evaluated by various rating scales. The QSM values in SN, RN, GP, and PT significantly increased in PD patients compared with the controls. Further subgroup comparison with the controls indicated that the iron content in SN and GP (paleostriatum) gradually elevated in the whole disease duration and was related to clinical features. While the iron content in RN and PT (neostriatum) only elevated significantly in ESP patients, further iron deposition was not obvious in ASP patients. Our study confirmed that QSM could be used as a disease biomarker and could be suitable for longitudinal monitoring. However, considering the temporal characteristics of iron deposition in neostriatum, iron deposition in the neostriatum should be paid more attention in the early stage of the disease, even in the preclinical stage, in future research.

Aims: The multipart Unified Parkinson's Disease Rating Scale is the standard instrument in clinical trials. A sum of scores for all items in 1 or more parts of the instrument is usually analysed. Without accounting for relative importance of individual items, this sum of scores conceivably does not optimize the power of the instrument. The aim was to compare the ability to detect drug effect in slowing down motor function deterioration, as measured by Part III of the Scale—motor examinations—between the item scores and the sum of scores. Methods: We used data from 423 patients in a Parkinson's disease progression trial to estimate the symptom severity by item response modelling; modelled symptom progression using the severity and the sum of scores; and conducted simulations to compare the sensitivity of detecting a broad range of hypothetical drug effects on progression using the severity and the sum of scores. Results: The severity endpoint was far more sensitive than the sum of scores for detecting treatment effects, e.g. requiring 275 vs. 625 patients per arm to achieve 60% probability of trial success for detecting a range of potential effects in a 2‐year trial. Nontremor items related to the left side of the body seemed most informative. The domain relevance of tremor items appeared questionable. Conclusion: This analysis generated clear evidence that longitudinal modelling of item scores can enhance trial efficiency and success. It also called for reassessing the placement of the tremor items in the instrument. [ABSTRACT FROM AUTHOR]

Studies have shown the spatial specificity of cranial iron deposition in different regions in Parkinson's disease (PD). However, the time-specific patterns of iron deposition are not yet clear. The purpose of this study was to investigate the time pattern of iron variations and its clinical relevance in multiple gray matter nuclei in PD using quantitative susceptibility mapping (QSM). Thirty controls and 33 PD patients were enrolled, namely, 11 cases of early stage of PD (ESP) and 22 cases of advanced stage of PD (ASP) according to the Hoehn-Yahr stages. The iron content in the subcortical nuclei covering substantia nigra (SN), red nucleus (RN), head of the caudate nucleus (CN), globus pallidus (GP), and putamen (PT) was measured using QSM, and the clinical symptoms of PD were evaluated by various rating scales. The QSM values in SN, RN, GP, and PT significantly increased in PD patients compared with the controls. Further subgroup comparison with the controls indicated that the iron content in SN and GP (paleostriatum) gradually elevated in the whole disease duration and was related to clinical features. While the iron content in RN and PT (neostriatum) only elevated significantly in ESP patients, further iron deposition was not obvious in ASP patients. Our study confirmed that QSM could be used as a disease biomarker and could be suitable for longitudinal monitoring. However, considering the temporal characteristics of iron deposition in neostriatum, iron deposition in the neostriatum should be paid more attention in the early stage of the disease, even in the preclinical stage, in future research. [ABSTRACT FROM AUTHOR]

Introduction: We investigated correlation between the retinal nerve fiber layer (RNFL) thickness and the severity of Parkinson's disease (PD). Methods: In this study, the RNFL thickness of 23 patients with Parkinson’s disease (PD) was compared to normal controls (NCs). PD severity was assessed by the MDS-UPDRS (movement disorder society Unified Parkinson Disease Rating Scale) rating scale thoroughly in all parts. RNFL is measured by Ocular Coherent tomography (OCT). Scatter plots were used to evaluate the relationship between disease severity and retinal thickness. Results: The findings of the study demonstrated that patients with PD had a significantly thinner average RNFL thickness compared with controls (P=0.035). Superior and inferior retinal quadrants were thinnest in PD compared with the healthy group (P=0.021 and P=0.045, respectively). The MDS-UPDRS had a significant reverse correlation with RNFL (r = -0.518, P=0.011) and its temporal quadrant (r = -0.594, P=0.003). Among all parts of MDS-UPDRS scale, Part III had the strongest correlation with OCT findings. Conclusion: A correlation was found between the severity of the disease and the thinning of RNFL. MDS-UPDRS Part III subscale had the strongest correlation with RNFL thickness. Temporal quadrant RNFL became thinner as Parkinson’s disease severity increased.

Abstract Background Motor dysfunction in patients with Parkinson disease (PD) is just the tip of the iceberg. Auditory and vestibular dysfunction in patients with PD gained much attention owing to them being one of the nonmotor symptoms. Aim To explore abnormalities of pure tone audiometry (PTA), brainstem auditory evoked potentials (BAEPs), vestibular evoked myogenic potential (VEMP), and videonystagmography (VNG) in patients with PD and their correlation with motor and cognitive dysfunction. Patients and methods The study was conducted on 20 patients with PD and 15 controls. Selected patients were subjected to evaluation of motor symptoms using Unified Parkinson’s Disease Rating Scale (UPDRS) and cognitive function using Parkinson disease-Cognitive Rating Scale (PD-CRS). PTA, BAEPs, cervical VEMPs, and VNG were carried out for all patients and controls. Results Patients with PD show higher mean hearing thresholds at all PTA frequencies in both ears than controls. Analysis of BAEP demonstrated that patients with PD have significantly prolonged absolute latencies of wave III and wave V and interpeak latencies of I–III and I–V in both ears than controls. VEMP findings revealed that patients have significantly delayed P13 and N23 latencies and smaller P13–N23 amplitude in both ears than controls. VNG findings showed canal paresis in 60% of patients with PD and nystagmus in 60% of patients with PD. Correlative results revealed statistically significant correlations between VEMP parameters and UPDRS as well as PD-CRS, but there were no statistically significant correlations between PTA frequencies or BAEP latencies and UPDRS or PD-CRS. Conclusion Auditory and vestibular dysfunction is common in PD but cannot be totally correlated with the motor and cognitive symptoms.

Background: Neuroinflammation plays a pathogenic role in Parkinson's disease (PD). Immunotherapies that restore brain homeostasis can mitigate neurodegeneration by transforming T cell phenotypes. Sargramostim has gained considerable attention as an immune transformer through laboratory bench to bedside clinical studies. However, its therapeutic use has been offset by dose-dependent adverse events. Therefore, we performed a reduced drug dose regimen to evaluate safety and to uncover novel disease-linked biomarkers during 5 days/week sargramostim treatments for one year. Methods: Five PD subjects were enrolled in a Phase 1b, unblinded, open-label study to assess safety and tolerability of 3 μg/kg/day sargramostim. Complete blood counts and chemistry profiles, physical examinations, adverse events (AEs), immune profiling, Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores, T cell phenotypes/function, DNA methylation, and gene and protein patterns were evaluated. Findings: Sargramostim administered at 3 μg/kg/day significantly reduced numbers and severity of AEs/subject/month compared to 6 μg/kg/day treatment. While MDS-UPDRS Part III score reductions were recorded, peripheral blood immunoregulatory phenotypes and function were elevated. Hypomethylation of upstream FOXP3 DNA elements was also increased. Interpretation: Long-term sargramostim treatment at 3 μg/kg/day is well-tolerated and effective in restoring immune homeostasis. There were decreased numbers and severity of AEs and restored peripheral immune function coordinate with increased numbers and function of Treg. MDS-UPDRS Part III scores did not worsen. Larger patient numbers need be evaluated to assess conclusive drug efficacy (ClinicalTrials.gov NCT03790670). Funding: The research was supported by community funds to the University of Nebraska Foundation and federal research support from 5 R01NS034239-25.

Background: The impact of Levodopa on the gut microbiota of Parkinson's disease (PD) patients has not been sufficiently addressed.Methods: We conducted a longitudinal study to examine the impact of Levodopa initiation on the gut microbiota composition of 19 PD patients who had not previously been exposed to Levodopa. Patients provided two stool samples prior to and two samples 90 days after starting Levodopa. Motor impairment (MDS-UPDRS Part III), diet, and other patient characteristics were assessed. 16S rRNA gene amplicon sequencing was used to characterize the microbiota. We examined, cross-sectionally and longitudinally, the associations between Levodopa use and alpha and beta diversity and performed feature-wise, multivariate modeling to identify taxa associated longitudinally with Levodopa use and with improvement in motor function after Levodopa administration.Results: We did not observe significant differences in alpha or beta diversity before vs. after initiation of Levodopa. In longitudinal feature-wise analyses, at the genus level, no taxa were significantly associated with Levodopa use after false discovery rate (FDR) correction (q < 0.05). We observed a marginally lower relative abundance of bacteria belonging to Clostridium group IV in PD patients who experienced a medium or large improvement in motor impairment in response to Levodopa compared to those with a small response [β = −0.64 (SE: 0.18), p-trend: 0.00015 p-FDR: 0.019].Conclusions: In this study, Levodopa was not associated with changes in microbiota composition in this longitudinal analysis. The association between abundance of Clostridium group IV and short-term motor symptom response to Levodopa is preliminary and should be investigated in larger, longer-term studies, that include a control group.

Background: The impact of Levodopa on the gut microbiota of Parkinson's disease (PD) patients has not been sufficiently addressed. Methods: We conducted a longitudinal study to examine the impact of Levodopa initiation on the gut microbiota composition of 19 PD patients who had not previously been exposed to Levodopa. Patients provided two stool samples prior to and two samples 90 days after starting Levodopa. Motor impairment (MDS-UPDRS Part III), diet, and other patient characteristics were assessed. 16S rRNA gene amplicon sequencing was used to characterize the microbiota. We examined, cross-sectionally and longitudinally, the associations between Levodopa use and alpha and beta diversity and performed feature-wise, multivariate modeling to identify taxa associated longitudinally with Levodopa use and with improvement in motor function after Levodopa administration. Results: We did not observe significant differences in alpha or beta diversity before vs. after initiation of Levodopa. In longitudinal feature-wise analyses, at the genus level, no taxa were significantly associated with Levodopa use after false discovery rate (FDR) correction (q < 0.05). We observed a marginally lower relative abundance of bacteria belonging to Clostridium group IV in PD patients who experienced a medium or large improvement in motor impairment in response to Levodopa compared to those with a small response [β = −0.64 (SE: 0.18), p-trend: 0.00015 p-FDR: 0.019]. Conclusions: In this study, Levodopa was not associated with changes in microbiota composition in this longitudinal analysis. The association between abundance of Clostridium group IV and short-term motor symptom response to Levodopa is preliminary and should be investigated in larger, longer-term studies, that include a control group. [ABSTRACT FROM AUTHOR]

Introduction: A dopamine agonist patch could be an important treatment option for Parkinson's disease. This study evaluated the long-term efficacy and safety of the ropinirole hydrochloride patch. The steady state plasma ropinirole concentration was also assessed.Methods: In a multicenter, open-label, uncontrolled study, Parkinson's disease patients with/without basal levodopa and with/without prior dopamine agonist therapy (any of these four regimens) received application of a ropinirole patch once daily for up to 52 weeks with unforced titration from 8 to 64 mg. For patients with prior dopamine agonist therapy, the initial dose of ropinirole patch was determined from the prior dopamine agonist dose by using a conversion table.Results: Most adverse events were mild or moderate. All application site adverse events were mild, except for moderate application site erythema in one patient. In patients with prior dopamine agonist therapy, switching to ropinirole patch did not lead to a significant early increase of adverse events. A change from baseline in the UPDRS Part III total score, the primary efficacy endpoint, showed improvement until Week 16 compared with baseline, followed by little subsequent change until Week 52, indicating maintenance of efficacy. The plasma ropinirole concentration was at steady state throughout the study period and showed a dose-proportional increase.Conclusion: Once-daily application of ropinirole patch showed long-term efficacy and safety (52 weeks) for Parkinson's disease. Switching from other dopamine agonists to ropinirole patch was effective and safe. The plasma ropinirole concentration was at steady state throughout the study period and showed a dose-proportional increase. [ABSTRACT FROM AUTHOR]

Purpose: Parkinson's Disease (PD) is a neuro-degenerative interminable issue causing dynamic loss of dopamine-creating synapses, which is one of the most far reaching ailments after Alzheimer's infection. In this paper, a system for the classification of Parkinson’s disease tremor using noninvasive measurement and frequency domain features is represented. Materials and Methods: Tremor time-series of Parkinson's disease patients were recorded via a smartphone’s accelerometer sensor. Short-Time Fourier Transform (STFT) was applied to transform the time-domain signal into the frequency domain with high time-frequency resolution. Several frequency features, including mean, max of power spectral density and side frequency have been extracted and by using the FDR algorithm combinations of features carried enough information to reliably assess the severity of tremor in Parkinson patients were determined. Results: Four different classifiers were implemented to estimate the severity of tremors based on the Unified Parkinson's Disease Rating Scale (UPDRS) in Parkinson's disease patients. Conclusion: Classifiers’ estimation was compared to clinical scores derived via neurologist UPDRS annotation on Parkinson's disease patients’ tremor. The best accuracy achieved was 95.91±1.51.

BACKGROUND: Non-motor symptoms (NMSs) were a real burden in Parkinson’s disease (PD) and contributed to severe disability, impaired quality of life (QoL), and shortened life expectancy. AIM: The aim of this study was to investigate the prevalence of NMSs in PD and their correlation of NMS with disease duration, severity, and Unified Parkinson′s Disease Rating Scale (UPDRS) motor score and their impact on patient’s QoL. MATERIALS AND METHODS: This was a prospective cross-sectional study. Sixty-four patients who were diagnosed by United Kingdom Parkinson′s Disease Brain Bank criteria were studied. Non-motor symptom scale (NMSS) analyzed NMS, and motor dysfunction was assessed by the UPDRS II and III during OFF condition and QoL by Parkinson’s Disease Questionnaire-39 (PDQ-39) questionnaire. RESULTS: The prevalence of NMS was 93.75% (n = 60). Most frequent NMS was difficulty in falling asleep (54.7%), urinary urgency (39%), and memory impairment (37.5%). Most disabling symptoms are difficulty in falling asleep (3.34 ± 4.1) and fatigue (2.48 ± 4.2). The total NMSS scores were correlated with Hoehn and Yahr stage, and Movement Disorder Society UPDRS and PDQ-39 scores, but not with duration of disease. Correlation between NMSS and PDQ-39 scores was stronger as compared to the relationship between UPDRS and PDQ-39 scores (r = 0.71 and 0.58, respectively, P = 0.00). CONCLUSION: This study showed the high prevalence of NMSs and value of NMS as predictors of QoL in patients with PD. Therefore, understanding the pathophysiology of these NMSs should be placed at the forefront to develop new therapeutic approaches by improving the QoL of patients with PD.

Background: Detailed knowledge about nonadherence to medication could improve medical care in elderly patients. We aimed to explore patterns and reasons for nonadherence in people with Parkinson's disease (PD) aged 60 years and older.Methods: Detailed clinical data and adherence (German Stendal Adherence with Medication Score) were assessed in 230 patients with PD (without dementia). Descriptive statistics were used to study reasons for nonadherence in detail, and general linear models were used to study associations between clusters of nonadherence and clinical parameters.Results: Overall, 14.2% (n = 32) of the patients were fully adherent, 66.8% (n = 151) were moderately nonadherent, and 19.0% (n = 43) showed clinically meaningful nonadherence. In the multivariable analysis, nonadherence was associated with a lower education level, higher motor impairment in activities of daily living, higher number of medications per day, and motor complications of PD. Three clusters of nonadherence were observed: 59 (30.4%) patients reported intentional nonadherence by medication modification; in 72 (37.1%) patients, nonadherence was associated with forgetting to take medication; and 63 (32.5%) patients had poor knowledge about the prescribed medication. A lower education level was mainly associated with modification of medication and poorer knowledge about prescribed medication, but not with forgetting to take medication. Patients with motor complications, which frequently occur in those with advanced disease stages, tend to be intentionally nonadherent by modifying their prescribed medication. Increased motor problems and a higher total number of drugs per day were associated with less knowledge about the names, reasons, and dosages of their prescribed medication.Conclusions: Elderly patients with PD report many reasons for intentional and non-intentional nonadherence. Understanding the impact of clinical parameters on different patterns of nonadherence may facilitate tailoring of interventions and counseling to improve outcomes.

Background: Depression and anxiety are non-motor symptoms of Parkinson's disease (PD) that are often overlooked and underrated. This study aimed to highlight the frequency and risk factors of depression and anxiety among subjects with PD. Methods: Sixty-four patients with PD who were diagnosed according to United Kingdom Parkinson's Disease Society (UKPDS) Brain Bank Criteria and 50 sex- and age-matched healthy control subjects are evaluated for depression and anxiety. PD severity and staging were assessed using Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn and Yahr scale. Depression and anxiety were diagnosed using DSM-IV TR criteria and scored using Hamilton Depression and Hamilton Anxiety Rating Scales (HAM-D and HAM-A). The World Health Organization Quality of Life (WHOQOL)-BREF was used to assess impact of depression and anxiety on quality of life. Results: 31.25% of patients with PD had depression while 40.6% of patients had anxiety disorder. Depression was higher in females and patients with history of depression and low socioeconomic status (SES). Anxiety was common in young patients and those who had history of anxiety. Overlap between depression and anxiety was recorded in 23.4%. Total UPDRS and Hoehn and Yahr scale accounted for 33.4% of variance for depression. Total UPDRS and earlier age of onset accounted for 39% of variance for anxiety. Advanced disease stage and severity were independent predictors for depression while disease severity and younger age of onset were the main predictors for anxiety. Depression and anxiety have a negative impact on the overall quality of life of PD patients especially on physical and psychosocial domains. Conclusion: Depression and anxiety are relatively common in PD. Female gender, low SES, and history of depression were the main risk factors for developing depression. Young age and history of anxiety were risk factors for anxiety. Both had negative impact on quality of life. [ABSTRACT FROM AUTHOR]

Advancing age and greater number of medical comorbidities are well-known risk factors for higher rates of surgical complications and undesirable outcomes. We sought to determine the risk of increasing medical comorbidities on surgical outcomes for patients with Parkinson disease undergoing deep brain stimulation (DBS) surgery. We retrospectively reviewed 107 consecutive patients who underwent DBS for Parkinson disease at Ochsner Medical Center in 2008–2018. Patients were stratified into 3 groups based on Elixhauser comorbidity index (ECI) at the time of surgery: 0, 1, or ≥2. Outcome measures were changes in Unified Parkinson's Disease Rating Scale III scores, changes in medications, and surgical complications. Analysis of variance, paired t test, and nonparametric equivalents were used for statistical analysis. Of patients, 31 (29.0%) had ECI score 0, 44 (41.1%) had ECI score 1, and 32 (29.9%) had ECI score ≥2. For all groups, Unified Parkinson's Disease Rating Scale III scores decreased significantly postoperatively (P = 0.0014, P < 0.0001, P < 0.0001). All groups had a reduction in mean levodopa equivalent daily dose after surgery; however, only the group with ≥2 comorbidities achieved statistical significance (P = 0.0026). The rate of postoperative complications was significantly correlated with comorbidity score on univariate logistic regression analysis (P = 0.0425). Our findings indicate that DBS is efficacious in patients with multiple medical comorbidities. However, patients with ≥1 medical comorbidities may be more likely to have complications. The most common observed complication was wound infection. Patients with medical comorbidities may still benefit significantly from DBS when performed at experienced centers. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate the base-peak difference in levodopa response for detecting patients with motor fluctuations in Parkinson's disease (PD). Methods: Two independent PD samples were evaluated at baseline and 2 h after the administration of the usual morning dose of levodopa using the Unified Parkinson's Disease Rating Scale part III (UPDRS-III). The presence of motor fluctuations was defined by the UPDRS-IV. We quantified the magnitude of motor variation as absolute (Δ) and percentage (Δ%) change in UPDRS-III scores. Optimal cut-offs for each index distinguishing patients with or without fluctuations were calculated on the exploratory population. The accuracy of the identified cut-offs was then verified in a testing population. Results: In the exploratory population (N = 26), the optimal cut-off for detecting fluctuations was a Δ of 6 points and a Δ% of 18.4%. When we applied the identified thresholds to the testing population (N = 139), we found a sensitivity of 93.8% (95% CI: 89.7 to 97.8) and a specificity of 91.2% (95% CI: 86.5 to 95.9) for Δ, 83.3% (95% CI: 77.1 to 89.5) and 86.8% (95% CI: 81.2 to 92.4) for Δ%, respectively. Conclusions: The assessment of levodopa usual morning dose response through the base-peak evaluation represents an accurate method for detecting parkinsonian patients with motor fluctuations, and for defining the Minimal Important Difference (MID) in levodopa response suggesting the presence of motor fluctuations in PD patients demanding further therapeutic interventions. [ABSTRACT FROM AUTHOR]