Motor Symptoms In Parkinson's Disease Patients Research Articles

Effectiveness and Safety of Meridian Activation Remedy System for Alleviating Motor Symptoms in Parkinson's Disease: an Observational Study.

Parkinson's disease (PD) lacks disease-modifying drugs or sustainable interventions, creating an unmet treatment need. Investigating complementary and alternative medicines aims to improve PD patients' quality of life by alleviating symptoms and delaying the course of the disease. In this single-center, prospective, observational, single-arm study, we aimed to assess the effectiveness and safety of acupuncture combined with exercise therapy and the Meridian Activation Remedy System (MARS). From March to October 2021, 13 PD patients with Hoehn and Yahr stages 1 to 3 were recruited. For 8 weeks, MARS intervention was carried out twice a week. T-statistics were used to evaluate functional near-infrared spectroscopy (fNIRS) and GAITRite outcomes. All of the remaining outcome variables were evaluated using the Wilcoxon signed-rank test. The MARS intervention significantly reduced PD patients' Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDSUPDRS) Part III score (from 20.0 ± 11.8 to 8.8 ± 5.5, p = 0.003), 10-meter walk test speed (from 9.5 ± 1.8 to 8.7 ± 1.3 seconds, p = 0.040), and timed up and go time (from 9.8 ± 1.8 to 8.9 ± 1.4 seconds, p = 0.040). Moreover, the MDS-UPDRS Part II, fNIRS hemodynamics, 360-degree turn test, fall efficacy scale, and Parkinson's Disease Questionnaire 39 scores improved but not significantly. All participants completed the 8-week intervention without any adverse reactions. An 8-week MARS intervention improved motor symptoms in PD patients. In particular, improvements in UPDRS Part III scores exhibited large clinically important differences. The findings are encouraging, and a randomized controlled trial will be conducted to determine the efficacy and cost-effectiveness of MARS intervention.

The effect of home-based exercise on motor and non-motor symptoms with Parkinson's disease patients: A systematic review and network meta-analysis.

To evaluate the effects of home-based exercise in Parkinson's disease (PD) patients. A network meta-analysis of randomized controlled trials. This study systematically searched PubMed, MEDLINE, Embase, Cochrane library and Web of Science. The quality of the literature was assessed using the Cochrane Risk of Bias 2.0 criteria. The data were pooled using R software. Results are presented as pooled standardized mean difference (SMD) with 95% confidence interval (CI). Thirty studies involving 2264 PD patients were included. Meta-analysis results showed that home-based exercise had a small effect in relieving overall motor symptoms in PD patients (SMD: -.28, 95% Crl [-.43; -.14]), improving quality of life (SMD = .15 [.03, .26]), walking speed (SMD = .30 [.04, .56]), balance ability (SMD = .18 [.04, .33]; p < .0001) and finger dexterity (SMD = .28 [.10, .46]). Mixed exercise (Mix) had better effects on improving motor symptoms and quality of life. In addition, the results of dose analysis showed that only mixed exercise exceeding 850 METs-min per week and more than 18 weeks can significantly alleviate the overall motor symptoms of PD patients. Home-based exercise was an effective form of therapy for alleviating motor symptoms. In addition, Mix appeared to be more suitable for PD patients engaging in home-based exercise. Existing evidence suggested that significant therapeutic effects were achieved with a Mix, with a weekly exercise volume exceeding 850 METs and a duration of more than 18 weeks. Home-based exercise had a small effect in relieving overall motor symptoms in PD patients, improving quality of life, walking speed, balance ability and finger dexterity. In terms of exercise dosage, we recommend the exercise period is no less than 18 weeks and the dose per is no less than 850 METs-min. No Patient or Public Contribution.

The effect of home-based exercise on motor symptoms, quality of life and functional performance in Parkinson's disease: a systematic review and meta-analysis

BackgroundFaced with the lack of physical activity caused by mandatory home isolation during special periods and patients' inconvenience in carrying out professionally supervised exercise, many home-based exercise programs have been developed. This systematic review and meta-analysis aimed to examine the effects of home-based exercise on measures of motor symptoms, quality of life and functional performance in Parkinson's disease (PD) patients.MethodsWe performed a systematic review and meta-analysis, and searched PubMed, MEDLINE, Embase, Cochrane library, and Web of Science from their inception date to April 1, 2023. The quality of the literature was assessed using PEDro's quality scale. The data was pooled using R software. Results are presented as pooled standardized mean difference (SMD) with 95% confidence interval (CI).ResultsA total of 20 studies involving 1885 PD patients were included. Meta-analysis results showed that home-based exercise had a small effect in relieving overall motor symptoms in PD patients (SMD = -0.29 [-0.45, -0.13]; P < 0.0001), improving quality of life (SMD = 0.20 [0.08, 0.32]; P < 0.0001), walking speed (SMD = 0.26 [0.05, 0.48]; P = 0.005), balance ability (SMD = 0.23 [0.10, 0.36]; P < 0.0001), finger dexterity (SMD = 0.28 [0.10, 0.46]; P = 0.003) and decreasing fear of falling (SMD = -0.29 [-0.49, -0.08]; P = 0.001). However, home-based exercise did not significantly relieve the overall motor symptoms of PD patients when the training period was less than 8 weeks and the total number of sessions was less than 30.ConclusionDuring times of limited physical activity due to pandemics such as COVID-19, home-based exercise is an alternative to maintain and improve motor symptoms in PD patients. In addition, for the minimum dose of home-based exercise, we recommend that the exercise period is no less than 8 weeks and the total number of sessions is no less than 30 times.Trial registrationPROSPERO registration number: CRD42022329780.

Structural changes in the retina and serum HMGB1 levels are associated with decreased cognitive function in patients with Parkinson's disease

BackgroundCognitive impairment is a serious nonmotor symptom in patients with Parkinson's disease (PD). Currently, there are few studies investigating the relationship of serum markers and retinal structural changes with cognitive function in PD. ObjectiveTo investigate the relationship between retinal structural changes, serum high mobility group box-1 (HMGB1) levels and cognitive function and motor symptoms in PD patients. MethodsEighty-nine participants, including 47 PD patients and 42 healthy subjects, were enrolled. PD patients were divided into Parkinson's disease with normal cognitive (PD-NC), Parkinson's disease with mild cognitive impairment (PD-MCI), and Parkinson's disease with dementia (PDD) groups. The motor and nonmotor symptoms of PD patients were evaluated with clinical scale. Serum HMGB1 levels were detected by enzyme-linked immunosorbent assay (ELISA), and ganglion cell-inner plexiform layer complex (GCIPL) thickness changes in the macula were quantitatively analyzed by swept source optical coherence tomography (SS-OCT) in all patients. ResultsCompared with the control group, the macular GCIPL (t = −2.308, P = 0.023) was thinner and serum HMGB1 (z = −2.285, P = 0.022) was increased in PD patients. Macular GCIPL thickness in patients with PD-MCI and PDD were significantly lower than that in PD-NC patients, but there were no significant difference between the PD-MCI and PDD groups. Serum HMGB1 levels in patients with PD-MCI and PDD were significantly higher than those in PD-NC patients, and serum HMGB1 levels in PDD patients were higher than those in PD-MCI patients. Correlation analysis showed that serum HMGB1 levels in PD patients were positively correlated with disease duration, HY stage, UPDRS-I score, UPDRS-III score, and UPDRS total score and negatively correlated with MOCA score. Macular GCIPL thickness was negatively correlated with HY stage and positively correlated with MOCA score, and macular GCIPL thickness was negatively correlated with serum HMGB1 level. Logistic regression analysis showed that elevated serum HMGB1 level, thinner macular GCIPL thickness, and higher HY stage were independent risk factors for Parkinson's disease with cognitive impairment (PD-CI). The areas under the receiver operating characteristic curve (AUC) for the serum HMGB1 level and macular GCIPL thickness-based diagnosis of PD-MCI, PDD and PD-CI based on in patients with PD were 0.786 and 0.825, 0.915 and 0.856, 0.852 and 0.841, respectively. The AUC for the diagnosis of PD-MCI, PDD and PD-CI with serum HMGB1 level and GCIPL thickness combined were 0.869, 0.967 and 0.916, respectively. ConclusionThe macular GCIPL thickness and serum HMGB1 level are potential markers of cognitive impairment in PD patients, and their combination can significantly improve the accuracy of the diagnosis of cognitive impairment in PD.

Monipar: movement data collection tool to monitor motor symptoms in Parkinson's disease using smartwatches and smartphones.

Parkinson's disease (PD) is a neurodegenerative disorder commonly characterized by motor impairments. The development of mobile health (m-health) technologies, such as wearable and smart devices, presents an opportunity for the implementation of clinical tools that can support tasks such as early diagnosis and objective quantification of symptoms. This study evaluates a framework to monitor motor symptoms of PD patients based on the performance of standardized exercises such as those performed during clinic evaluation. To implement this framework, an m-health tool named Monipar was developed that uses off-the-shelf smart devices. An experimental protocol was conducted with the participation of 21 early-stage PD patients and 7 healthy controls who used Monipar installed in off-the-shelf smartwatches and smartphones. Movement data collected using the built-in acceleration sensors were used to extract relevant digital indicators (features). These indicators were then compared with clinical evaluations performed using the MDS-UPDRS scale. The results showed moderate to strong (significant) correlations between the clinical evaluations (MDS-UPDRS scale) and features extracted from the movement data used to assess resting tremor (i.e., the standard deviation of the time series: r = 0.772, p < 0.001) and data from the pronation and supination movements (i.e., power in the band of 1-4 Hz: r = -0.662, p < 0.001). These results suggest that the proposed framework could be used as a complementary tool for the evaluation of motor symptoms in early-stage PD patients, providing a feasible and cost-effective solution for remote and ambulatory monitoring of specific motor symptoms such as resting tremor or bradykinesia.

Novel ultrasound neuromodulation therapy with transcranial pulse stimulation (TPS) in Parkinson's disease: a first retrospective analysis.

Transcranial Pulse Stimulation (TPS) has been recently introduced as a novel ultrasound neuromodulation therapy with the potential to stimulate the human brain in a focal and targeted manner. Here, we present a first retrospective analysis of TPS as an add-on therapy for Parkinson's disease (PD), focusing on feasibility, safety, and clinical effects. We also discuss the placebo response in non-invasive brain stimulation studies as an important context. This retrospective clinical data analysis included 20 PD patients who received ten sessions of TPS intervention focused on the individual motor network. Safety evaluations were conducted throughout the intervention period. We analyzed changes in motor symptoms before and after TPS treatment using Unified Parkinson's Disease Rating Scale part III (UPDRS-III). We found significant improvement in UPDRS-III scores after treatment compared to baseline (pre-TPS: 16.70 ± 8.85, post-TPS: 12.95 ± 8.55; p < 0.001; Cohen's d = 1.38). Adverse events monitoring revealed no major side effects. These preliminary findings suggest that TPS can further improve motor symptoms in PD patients already on optimized standard therapy. Findings have to be evaluated in context with the current literature on placebo effects.

The guiding effect of local field potential during deep brain stimulation surgery for programming in Parkinson's disease patients.

Parkinson's disease (PD) patients undergoing deep brain stimulation (DBS) surgery require subsequent programming, which is complex and cumbersome. The local field potential (LFP) in the deep brain is associated with motor symptom improvement. The current study aimed to identify LFP biomarkers correlated with improved motor symptoms in PD patients after DBS and verify their guiding role in postoperative programming. Initially, the study included 36 PD patients undergoing DBS surgery. Temporary external electrical stimulation was performed during electrode implantation, and LFP signals around the electrode contacts were collected before and after stimulation. The stimulating contact at 6 months of programming was regarded as the optimal and effective stimulating contact. The LFP signal of this contact during surgery was analyzed to identify potential LFP biomarkers. Next, we randomly assigned another 30 PD patients who had undergone DBS to physician empirical programming and LFP biomarker-guided programming groups and compared the outcomes. In the first part of the study, LFP signals of electrode contacts changed after electrical stimulation. Electrical stimulation reduced gamma energy and the beta/alpha oscillation ratio. The different programming method groups were compared, indicating the superiority of beta/alpha oscillations ratio-guided programming over physician experience programming for patients' improvement rate (IR) of UPDRS-III. There were no significant differences in the IR of UPDRS-III, post-LED, IR-PDQ39, number of programmings, and the contact change rate between the gamma oscillations-guided programming and empirical programming groups. Overall, the findings reveal that gamma oscillations and the beta/alpha oscillations ratio are potential biomarkers for programming in PD patients after DBS. Instead of relying solely on spike action potential signals from single neurons, LFP biomarkers can provide the appropriate depth for electrode placement.

The effect of Parkin gene S/N 167 polymorphism on resting spontaneous brain functional activity in Parkinson's Disease

BackgroundGenetic susceptibility plays a significant role in Parkinson's disease (PD) development. Carriers of the Parkin S/N167 mutation may have an increased risk of PD and altered spontaneous brain activity. ObjectiveThis study aims to investigate the potential pathogenesis of PD through a comparative analysis of the amplitude of low-frequency fluctuations (ALFF) in resting-state functional magnetic resonance imaging (rs-fMRI) of subjects with Parkin gene S/N 167 polymorphisms, and to examine the association between spontaneous brain activity and clinical scale scores of PD. MethodsA total of 69 PD patients and 84 healthy controls (HC) were included in the study. Each subject was genotyped for the Parkin gene S/N 167 polymorphism and underwent rs-fMRI scans. ALFF analysis was employed to evaluate the relationship among genotypes, interactive brain regions, and clinical symptoms in PD. ResultsPD patients exhibited decreased ALFF values in the right anterior lobe and vermis of the cerebellum compared to HC. No significant interaction was found between the gene's main effect and the “group × genotype” effect on brain ALFF values. One-factor ANOVA revealed no significant difference in ALFF values between PD subgroups; however, the ALFF values in the right anterior lobe and vermis of the cerebellum were lower in the PD-G and PD-GA groups compared to the HC-G and HC-GA groups. Spearman correlation analysis demonstrated that ALFF values in the PD-GG and PD-GA groups were negatively associated with UPDRS-III scores in the bilateral lingual gyrus (Lingual R/L). ConclusionParkin gene S/N 167 polymorphisms may influence brain functional activity in specific brain regions, and ALFF values are associated with motor symptoms in PD patients.

Oxidative Stress and Neuroinflammation in Parkinson's Disease: The Role of Dopamine Oxidation Products.

Parkinson's disease (PD) is a chronic neurodegenerative condition affecting more than 1% of people over 65 years old. It is characterized by the preferential degeneration of nigrostriatal dopaminergic neurons, which is responsible for the motor symptoms of PD patients. The pathogenesis of this multifactorial disorder is still elusive, hampering the discovery of therapeutic strategies able to suppress the disease's progression. While redox alterations, mitochondrial dysfunctions, and neuroinflammation are clearly involved in PD pathology, how these processes lead to the preferential degeneration of dopaminergic neurons is still an unanswered question. In this context, the presence of dopamine itself within this neuronal population could represent a crucial determinant. In the present review, an attempt is made to link the aforementioned pathways to the oxidation chemistry of dopamine, leading to the formation of free radical species, reactive quinones and toxic metabolites, and sustaining a pathological vicious cycle.

Promising biomarkers and therapeutic targets for the management of Parkinson's disease: recent advancements and contemporary research.

Parkinson's disease (PD) is one of the progressive neurological diseases which affect around 10 million population worldwide. The clinical manifestation of motor symptoms in PD patients appears later when most dopaminergic neurons have degenerated. Thus, for better management of PD, the development of accurate biomarkers for the early prognosis of PD is imperative. The present work will discuss the potential biomarkers from various attributes covering biochemical, microRNA, and neuroimaging aspects (α-synuclein, DJ-1, UCH-L1, β-glucocerebrosidase, BDNF, etc.) for diagnosis, recent development in PD management, and major limitations with current and conventional anti-Parkinson therapy. This manuscript summarizes potential biomarkers and therapeutic targets, based on available preclinical and clinical evidence, for better management of PD.

Proteomic Analysis of Protective Effects of Dl-3-n-Butylphthalide against mpp + -Induced Toxicity via downregulating P53 pathway in N2A Cells

BackgroundDl-3-n-butylphthalide (NBP) is an important medial therapy for acute ischemic stroke in China. Recent studied have revealed that NBP not only rescued the loss of dopaminergic neurons in cellular and animal models of Parkinson's disease (PD), but also could improve motor symptoms in PD patients. However, the protective mechanism is not fully understood. P53 is a multifunctional protein implicated in numerous cellular processes, including apoptosis, DNA repair, mitochondrial functions, redox homeostasis, autophagy and protein aggregations. In PD, p53 integrated with various neurodegeneration-related signals inducing neuronal loss, indicating the suppression of P53 might be a promising target for PD treatment. Therefore, the purpose of the current study was to systemically screen new therapeutic targets of NBP in PD.MethodIn our study, we constructed mpp + induced N2A cells to investigate the benefit effect of NBP in PD. MTT assay was performed to evaluate the cell viability; TMT-based LC–MS/MS was applied to determine the different expressed proteins (DEPs) of NBP pretreatment; online bioinformatics databases such as DAVID, STRING, and KEGG was used to construe the proteomic data. After further analyzed and visualized the protein–protein interactions (PPI) by Cytoscape, DEPs were verified by western blot.ResultA total of 5828 proteins were quantified in the comparative proteomics experiments and 417 proteins were considered as DEPs (fold change > 1.5 and p < 0.05). Among the 417 DEPs, 140 were upregulated and 277 were downregulated in mpp + -induced N2A cells with NBP pretreatment. KEGG pathway analysis indicated that lysosome, phagosome, apoptosis, endocytosis and ferroptosis are the mainly enriched pathways. By using MCL clustering in PPI analysis, 48 clusters were generated and the subsequent KEGG analysis of the top 3 clusters revealed that P53 signaling pathway was recognized as the dominant pathway for NBP treatment.ConclusionNBP significantly relived mpp + -induced cell toxicity. The neuroprotective role of NBP was implicated with P53 signaling pathway in some extent. These findings will reinforce the understanding of the mechanism of NBP in PD and identify novel therapeutic targets.

Unveiling the Impact of Outpatient Physiotherapy on Specific Motor Symptoms in Parkinson's Disease: A Prospective Cohort Study.

Understanding how outpatient physiotherapy impacts on specific motor symptoms in Parkinson's disease (PD) is important for multidisciplinary care, but these points have not been clarified. We investigated the impact of outpatient physiotherapy on individual motor symptoms in PD patients. Fifty-five PD patients participated in the prospective cohort study, which examined the changes in motor symptoms after 90 min of outpatient physiotherapy program (1×/week for 10 weeks) and at 3 months follow-up. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score and tremor, rigidity, bradykinesia, and axial scores were assessed and compared pre-intervention, post-intervention, and at follow-up. Significant level was set at 0.05. Their MDS-UPDRS motor score and axial score significantly decreased post-intervention and at the follow-up. In the analysis differentiating effects based on the severity of motor symptoms according to the MDS-UPDRS motor score, only the moderate-severe group showed significant decreases in their MDS-UPDRS motor score, bradykinesia, and axial scores post-intervention, as well as in their MDS-UPDRS motor score, rigidity, bradykinesia, and axial scores at the follow-up. These findings suggest the outpatient physiotherapy might provide benefits, particularly in managing axial symptoms and bradykinesia, for community dwelling PD patients with moderate-severe motor symptoms within a multidisciplinary care framework.

Adaptive deep brain stimulation for Parkinson's disease: looking back at the past decade on motor outcomes.

Adaptive deep brain stimulation (aDBS) has been reported to be an effective treatment for motor symptoms in patients with Parkinson's disease (PD). However, it remains unclear whether and in which motor domain aDBS provides greater/less benefits than conventional DBS (cDBS). To conduct a meta-analysis and systematic review to explore the improvement of the motor symptoms of PD patients undergoing aDBS and the comparison between aDBS and cDBS. Nineteen studies from PubMed, Embase, and the Cochrane Library database were eligible for the main analysis. Twelve studies used quantitative plus qualitative analysis; seven studies were only qualitatively analyzed. The efficacy of aDBS was evaluated and compared to cDBS through overall motor function improvements, changes in symptoms of rigidity-bradykinesia, dyskinesia, tremor, and speech function, and total electrical energy delivered (TEED). The overall motor improvement and TEED were investigated through meta-analyses, while other variables were investigated by systematic review. Quantitative analysis showed that aDBS, with a reduction of TEED (55% of that of cDBS), significantly improved motor functions (33.9%, p < 0.01) and may be superior to cDBS in overall motor improvement (p = 0.002). However, significant publication bias was detected regarding the superiority (p = 0.006, Egger's test). In the qualitative analysis, rigidity-bradykinesia, dyskinesia, and speech function outcomes after aDBS and cDBS were comparable. Beta-based aDBS may not be as efficient as cDBS for tremor control. aDBS can effectively relieve the clinical symptoms of advanced PD as did cDBS, at least in acute trials, delivering less stimulation than cDBS. Specific symptoms including tremor and axial disability remain to be compared between aDBS and cDBS in long-term studies.

Safety and effectiveness of istradefylline as add-on therapy to levodopa in patients with Parkinson's disease: Final report of a post-marketing surveillance study in Japan

IntroductionIstradefylline is approved in Japan and the US for treatment of Parkinson's disease (PD) in adult patients who experience the wearing-off phenomenon while receiving levodopa; however, safety and efficacy data for real-world clinical use are lacking. MethodsWe report the final results of a prospective, long-term, post-marketing surveillance study of istradefylline adjunct to levodopa for adults with PD experiencing the wearing-off phenomenon. Patients across 214 study sites initiating treatment with oral istradefylline once-daily 20- or 40-mg were followed-up for 1 year. We collected demographic data, disease and treatment histories, and recorded adverse events and adverse drug reactions (ADRs). The priority survey item was the occurrence of psychiatric ADRs. Effectiveness was evaluated by the physician's global and motor function assessments. ResultsCase report forms were collected for 1320 patients, and the safety and effectiveness analysis sets included 1318 and 1284 patients, respectively. The mean age was 71.5 years and 56.2% of patients were women. A total of 274 patients (20.8%) experienced an ADR, 39 patients had a serious ADR, and 7 patients had a fatal ADR that was considered not related to istradefylline. Common ADRs included dyskinesia, hallucination, and visual hallucination. Sixty-five patients (4.9%) experienced a psychiatric ADR. Istradefylline was effective (physician-rated) in 59.8% of patients, and most patients had reduced or unchanged off-time duration, improved or unchanged off-time symptoms, and improved or unchanged motor symptoms. ConclusionIstradefylline safely and effectively improves motor symptoms in PD patients experiencing the wearing-off phenomenon with levodopa therapy in the real-world setting.

Motor progression marker for newly diagnosed drug-naïve patients with Parkinson's disease: A resting-state functional MRI study.

The effective early prediction of clinical outcomes of Parkinson's disease (PD) is of great significance in the implementation of appropriate interventions. We aimed to propose a method based on the use of baseline resting-state functional characteristics (i.e., fractional amplitude of low-frequency fluctuations, fALFF) to predict motor progression in PD patients. Resting-state functional magnetic resonance imaging was performed on 48 newly-diagnosed drug-naïve PD patients and 27 age- and sex- matched healthy controls (HCs). Two PD subgroups were defined with different annual increase of Unified PD Rating Scale Part III motor scores. Least absolute shrinkage and selection operator regression analysis was performed to explore the baseline region-functional indicators for PD discrimination as well as the predictors for future motor deficits. Two significant models composed of baseline fALFF values from cerebral subregions were proposed. The classification model that distinguished PD patients from HCs (area under the curve [AUC]=0.897) showed the most significant imaging characteristics in the putamen and precentral gyrus. The other prediction model that evaluated the degree of future deterioration of motor symptoms in PD patients (AUC=0.916) showed the most significant imaging characteristics in the superior occipital gyrus and caudate nucleus. Furthermore, the increased regional function in bilateral caudate nuclei was correlated with the lower annual increase in motor deficits in all PD patients. The caudate nucleus might be the core region responsible for future motor deficits in newly-diagnosed PD patients, which may aid the development of disease progression preventive strategies in clinical practice.

Do neuropsychiatric fluctuations temporally match motor fluctuations in Parkinson's disease?

In Parkinson's disease (PD), non-motor fluctuations (NMFs), especially neuropsychiatric fluctuations, often coexist with motor fluctuations (MFs) but are often under-recognized by physicians and patients. To investigate the relationship between MFs and neuropsychiatric fluctuations in PD. PD patients with MFs and NMFs were enrolled. The Parkinson's Kinetigraph (PKG), a wearable device to detect MFs and dyskinesia, was used to confirm and measure MFs. The Neuropsychiatric Fluctuation Scale (NFS), a scale composed by subscores for both the ON and OFF neuropsychiatric states, was used to identify and quantify neuropsychiatric fluctuations. Patients were asked to wear the PKG for six consecutive days to identify the ON and OFF motor periods, and then to fill the NFS during the ON and OFF motor periods for three consecutive days wearing the PKG. The PKG system provided a bradykinesia score (BKS) and a dyskinesia score (DKS). Relations between BKS, DKS, and ON and OFF NFS subscores were analyzed. In 18 PD patients, anxiety, apathy, and depression characterized the OFF condition, whereas self-confidence, competency, and interest in doing things were typically in the ON condition. There was a positive correlation between the BKS and the OFF NFS subscores (p = 0.036, r = 0.51), whereas no correlation was found between the DKS and the ON NFS subscores (p = 0.38, r = 0.22). Neuropsychiatric fluctuations temporarily matched the OFF MFs only in the OFF condition. These findings are useful to better manage OFF NMSs and support the need to further investigate associations between non-motor and motor symptoms in PD patients.

Comparison of pramipexole and citalopram in the treatment of depression in Parkinson's disease: A randomized parallel-group trial.

Background:Depression is one of the most common neuropsychiatric symptoms in Parkinson's disease (PD). There is little evidence to guide depression treatment in these patients. The aim of this study was to compare citalopram and pramipexole in reducing depressive symptoms in patients with PD.Materials and Methods:In the present 8-week randomized trial, we compared the efficacy of pramipexole versus citalopram in the treatment of depression in PD patients. For this purpose, 44 PD patients with depression randomly received open-label oral citalopram tablets or pramipexole and their depression, quality of life, and daytime sleepiness scores were evaluated at baseline and after the 8-week trial period.Results:The median age of the patients was 64 years, and about 85% of them were male in both groups. The Beck Depression Inventory score, Parkinson's disease summary index (PDSI), and Epworth Sleepiness Scale were significantly decreased (P < 0.05) in both citalopram and pramipexole groups throughout this period and without significant difference (P > 0.05) between these two groups, except for PDSI score which showed significant improvement in pramipexole group compared with citalopram group (P < 0.0001, r = 0.319). There were neither serious adverse effects nor treatment discontinuation due to the adverse effects.Conclusion:The results indicated that both citalopram and pramipexole were effective in the alleviation of depression and improving the quality of life in PD patients; however, pramipexole was seemed to be slightly more beneficial on quality of life in these patients. Therefore, pramipexole seems to be an effective treatment for depression in addition to its benefits for motor symptoms of PD patients.

Comparing subjective and objective response to medications in Parkinson's disease patients using the Personal KinetiGraph™

BackgroundManagement of motor symptoms in Parkinson's Disease(PD) relies on subjective information provided by patients, the quality of which can be affected by many factors. RationaleObjective data collected during daily life could complement this information and improve management of motor symptoms. ObjectivesTo assess the usefulness of the Personal KinetiGraph (PKG) in characterizing the intensity and timing of motor symptoms in PD patients. MethodsRetrospective study of all PD patients followed at a tertiary academic movement disorders center assessed by PKG between December 1, 2016 and October 30, 2018. PKG was worn for 7 days prior to the clinical visit. We compared the information obtained from the interview and the clinical visit, and assessed the impact of the PKG on treatment decision making. Results170 PKG results were reviewed. PKG complemented patient input in 82.9%(141/170) and led to medication changes in 71%(100/141) of the complemented inputs. PKG contributed the least to correcting or complementing patients’ input when patients self-reported as undertreated (22%) and the most when patient were unable to answer all questions regarding motor response to individual doses (100%) (Fisher, p < 0.0001). The majority of patient undergoing 3 or 4 PKG encounters did not reach a controlled state as defined by PKG until the 3rd or 4th encounter, suggesting that repeated use of the PKG might be needed to help optimize motor control as therapy changes done after one encounter might not be enough. ConclusionsPKG might be useful in supplementing patient-provided information for accurate assessment and treatment plan.

Assessment of Motor Dysfunction with Virtual Reality in Patients Undergoing [123I]FP-CIT SPECT/CT Brain Imaging.

[123I]FP-CIT SPECT has been valuable for distinguishing Parkinson disease (PD) from essential tremor. However, its performance for quantitative assessment of motor dysfunction has not been established. A virtual reality (VR) application was developed and compared with [123I]FP-CIT SPECT/CT for detection of severity of motor dysfunction. Forty-four patients (21 males, 23 females, age 64.5 ± 12.4) with abnormal [123I]FP-CIT SPECT/CT underwent assessment of bradykinesia, activities of daily living, and tremor with VR. Support vector machines (SVM) machine learning models were applied to VR and SPECT data. Receiver operating characteristic (ROC) analysis demonstrated greater area under the curve (AUC) for VR (0.8418, 95% CI 0.6071–0.9617) compared with brain SPECT (0.5357, 95% CI 0.3373–0.7357, p = 0.029) for detection of motor dysfunction. Logistic regression identified VR as an independent predictor of motor dysfunction (Odds Ratio 326.4, SE 2.17, p = 0.008). SVM for prediction of the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III) demonstrated greater R-squared of 0.713 (p = 0.008) for VR, compared with 0.0764 (p = 0.361) for brain SPECT. This study demonstrates that VR can be safely used in patients prior to [123I]FP-CIT SPECT imaging and may improve prediction of motor dysfunction. This test has the potential to provide a simple, objective, quantitative analysis of motor symptoms in PD patients.

Correlates of polyneuropathy in Parkinson's disease.

ObjectivePrevious studies in Parkinson’s disease (PD) patients have demonstrated a high prevalence of polyneuropathy (PNP) and pronounced alpha‐Synuclein pathology in dermal nerve fibers already at early disease stages. The aim of this study was to analyze associations between the prevalence and severity of PNP with nonmotor and motor symptoms in PD patients.MethodsFifty PD patients were characterized comprehensively for the presence of clinical symptoms (nonmotor and motor), electrophysiologic alterations and – for the first time – using high‐resolution ultrasound of peripheral nerves.ResultsSixty‐two percent of PD patients showed electrophysiological pathology of PNP. The prevalence of patient‐reported PNP symptoms was 86% and was particularly present in patients with longer disease duration, compromised scores of nonmotor and motor symptoms as well as with a negative evaluation of quality of life. Seventy‐five percent of patients showed morphologic alterations similar to axonal PNP in high‐resolution ultrasound compared to healthy controls.InterpretationThe study demonstrates the high burden of peripheral nervous system disease in Parkinson's disease. It advocates further studies to delineate the underlying pathophysiological mechanisms in order to optimize treatment approaches for PD, including the associated PNP.