Movement Disorder Society-Unified Parkinson's Disease Rating Scale Research Articles

Science, Medicine, and the Anesthesiologist

Science, Medicine, and the Anesthesiologist

Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease

Current treatments manage symptoms of Parkinson disease (PD), but no known treatment slows disease progression. Preclinical and epidemiological studies support the potential use of statins as disease-modifying therapy. To determine whether simvastatin has potential as a disease-modifying treatment for patients with moderate PD. This randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial, was conducted between March 2016 and May 2020 within 23 National Health Service Trusts in England. Participants aged 40 to 90 years with a diagnosis of idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon were included. Data were analyzed from May 2020 to September 2020, with additional analysis in February 2021. Participants were allocated 1:1 to simvastatin or matched placebo via a computer-generated random sequence, stratified by site and Hoehn and Yahr stage. In the simvastatin arm, participants entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout period. The prespecified primary outcome was 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score measured while not taking medication (high scores indicate worse outcome). The primary futility analysis included participants who commenced the 80-mg phase and had valid primary outcome data. The safety analysis included all participants who commenced trial treatment and is reported by dose at time of event. Of 332 patients assessed for eligibility, 32 declined and 65 were ineligible. Of 235 recruited participants, 97 (41%) were female, 233 (99%) were White, and the mean (SD) age was 65.4 (9.4) years. A total of 216 patients progressed to the 80-mg dose. Primary outcome analysis (n = 178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months compared with the placebo group (1.52 points; 2-sided 80% CI, -0.77 to 3.80; 1-sided futility test P = .006). A total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs were reported for participants receiving 0-mg simvastatin; 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin. Four participants withdrew from the trial because of an AE. In this randomized clinical trial, simvastatin was futile as a disease-modifying therapy in patients with PD of moderate severity, providing no evidence to support proceeding to a phase 3 trial. ISRCTN Identifier: 16108482.

Effects of MOTOmed® movement therapy on the motor function and main symptoms of patients with Parkinson’s disease: a systematic review

Introduction: Scientific findings show immediate improvements after forced assisted cycling at high pedaling speeds of up to 90 revolutions per minute in patients with Parkinson's Disease, thus this review aimed to estimate the efficacy of MOTOmed® movement therapy. to increase motor function and alleviate the main symptoms in these patients. Methods: Systematic review including randomized controlled trials examining MOTOmed® movement therapy interventions, alone or as an adjunct to rehabilitation, for patients with Parkinson's disease. The risk of bias assessment tool followed the recommendations of the Cochrane Handbook 5.1.0. All included studies reported the effects of mobility as primary outcomes. Standardized mean differences or mean differences with corresponding 95% confidence intervals (CI) were calculated. Results: In total, 7 trials with a total of 206 patients were included in the analysis. All studies were of moderate quality. MOTOmed® movement therapy resulted in statistically significant improvements in the MDS-UPDRS (Movement Disorder Society-Unified Parkinson Disease Rating Scale) Motor III score (p<0.05); Upper limb MDS-UPDRS score (p<0.05); Total MDS-UPDRS (p<0.04): Upper body function (p<0.007); bradykinesia (p<0.044); Cycling variables: higher cadence (p<0.001); Timed up and done (p>0.05); tremor score (p<0.05); Walking time (p<0.05); Gait steps (p<0.05); Pronation and supination (p<0.05); Parkinson's Disease Questionnaire -PQD8 (bandages and depressions p<0.05); Gait analysis: speed (p<0.000), stride length (p<0.000), monopedal posture (p<0.000), swing phase (p<0.000); Biodex® Balance System: Clinical Test of Sensory Integration of Balance-CTSIB1 (p<0.007). Conclusion: MOTOmed® movement therapy alone or combined with standard rehabilitation improves motor function and main symptoms in patients with Parkinson's disease. Keywords: Parkinson´s disease, MOTOmed®, Physical Therapy, Physical Activity, Rehabilitation.

Clinically important change on the Unified Dyskinesia Rating Scale among patients with Parkinson's disease experiencing dyskinesia.

The Unified Dyskinesia Rating Scale (UDysRS) evaluates dyskinesia in patients with Parkinson's disease (PD). A minimal clinically important change (MCIC)-the smallest change in a treatment outcome that a patient considers important-remains undefined for the UDysRS. To utilize pivotal amantadine delayed-release/extended-release (DR/ER) trial data to derive MCICs for the UDysRS total score in patients with PD experiencing dyskinesia. Pivotal trials included PD patients with ≥1 h daily ON time with troublesome dyskinesia and baseline scores ≥2 on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV, item 4.2. Patients randomized to amantadine DR/ER or placebo completed two consecutive 24-h diaries before each clinic visit and were evaluated during ON time with dyskinesia using the UDysRS, MDS-UPDRS, and Clinician Global Impression of Change (CGI-C). The UDysRS changes from baseline to week 12 were anchored to corresponding changes in MDS-UPDRS item 4.2 scores. A minimal clinically important improvement in the CGI-C and diary-reported ON time with troublesome dyskinesia (≥0.5 h) were supportive anchors. Receiver operating characteristic curves determined the UDysRS change values optimizing sensitivity and specificity to at least minimal improvement on each anchor. The analyses included 196 patients. Week 12 UDysRS total score reduction of ≥8 points corresponded to at least minimal MDS-UPDRS item 4.2 improvement. UDysRS reduction of ≥9 points corresponded to decreased ON time with troublesome dyskinesia of ≥0.5 h per patient diaries, and UDysRS reduction of ≥10 points corresponded to at least minimal improvement on the CGI-C. Anchored to the MDS-UPDRS Part IV, item 4.2, an 8-point reduction in the UDysRS total score can be considered an MCIC for PD patients with dyskinesia.

An Evaluation of KELVIN, an Artificial Intelligence Platform, as an Objective Assessment of the MDS UPDRS Part III.

Parkinson's disease severity is typically measured using the Movement Disorder Society Unified Parkinson's disease rating scale (MDS-UPDRS). While training for this scale exists, users may vary in how they score a patient with the consequence of intra-rater and inter-rater variability. In this study we explored the consistency of an artificial intelligence platform compared with traditional clinical scoring in the assessment of motor severity in PD. Twenty-two PD patients underwent simultaneous MDS-UPDRS scoring by two experienced MDS-UPDRS raters and the two sets of accompanying video footage were also scored by an artificial intelligence video analysis platform known as KELVIN. KELVIN was able to produce a summary score for 7 MDS-UPDRS part 3 items with good inter-rater reliability (Intraclass Correlation Coefficient (ICC) 0.80 in the OFF-medication state, ICC 0.73 in the ON-medication state). Clinician scores had exceptionally high levels of inter-rater reliability in both the OFF (0.99) and ON (0.94) medication conditions (possibly reflecting the highly experienced team). There was an ICC of 0.84 in the OFF-medication state and 0.31 in the ON-medication state between the mean Clinician and mean Kelvin scores for the equivalent 7 motor items, possibly due to dyskinesia impacting on the KELVIN scores. We conclude that KELVIN may prove useful in the capture and scoring of multiple items of MDS-UPDRS part 3 with levels of consistency not far short of that achieved by experienced MDS-UPDRS clinical raters, and is worthy of further investigation.

Screening for non-motor symptoms in Egyptian patients with Parkinson’s disease

BackgroundMost of the patients with Parkinson’s disease (PD) suffer from non-motor symptoms (NMS). Despite their marked effect on patients’ quality of life, NMS remain under-estimated by physicians, patients and caregivers. The aim of this study was to suggest a battery to screen for the presence of NMS in PD patients in the setting of an outpatient clinic and to assess the NMS of PD in Egyptian patients and factors affecting them.ResultsThis study was conducted on 50 patients with PD, 35 males (70%) and 15 females (30%) whom their age ranged from 36 to 80 years with a mean of 62.88 ± 8.74 years. All patients were assessed using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Apathy Scale (AS), Montreal Cognitive Assessment (MOCA), Hamilton Depression Rating Scale (HDRS) and Parkinson’s Disease Sleep Scale (PDSS). The mean age at disease onset was 59.10 ± 9.34 years and the mean disease duration was 3.76 ± 3.16 years. 98% of patients (49 out of 50) had at least one non-motor symptom. The mean MDS-UPDRS scores were 15.74 ± 7.93 for part I, 17.94 ± 11.61 for part II and 42.32 ± 22.74 for part III. The mean score for AS was 9.90 ± 10.66 with 70% of patients considered apathetic. The mean MOCA score was 21.12 ± 4.73 with 38 patients (76%) found to be cognitively impaired. The mean HDRS score was 12.26 ± 8.52 with 34 patients (68%) found to be depressed. The mean PDSS score was 92.22 ± 32.53 with sleep disturbances found in 38 patients (76%). A statistically significant negative correlation was found between the HDRS and PDSS scores (P value < 0.001). Age of patients, age at disease onset and disease duration were not correlated to MDS-UPDRS, AS, MOCA, HDRS and PDSS scores.ConclusionsMost of the patients with PD were found to suffer from NMS including apathy, cognitive impairment, depression and sleep disturbances. Physicians need to screen their PD patients for NMS on regular basis using the appropriate tools. Self-administered questionnaires could function as reliable screening tools for NMS in PD patients.

Are static posturography-assisted biofeedback exercises effective in Parkinson's disease?

Parkinson disease (PD) is a progressive condition that causes disorders in movement and balance. To evaluate the effectiveness of static posturography-assisted biofeedback exercises in PD-related balance disorder. We screened 83 patients, 48 of whom were enrolled, and 41 completed the study. The sample was randomized into two groups, one submitted to static posturography-assisted biofeedback exercises and the other, to a conventional exercise program. The patients in the biofeedback group (n = 20) performed biofeedback exercises in addition to conventional balance exercises. Those in the conventional exercise group (n = 21) performed classic balance exercises. Both groups were treated for 20 minutes per session 3 times a week for 6 weeks. The patients were evaluated using the Hoehn and Yahr Scale, the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the Berg Balance Scale (BBS), the Tinetti Gait and Balance Assessment (TGBA), the Timed Up and Go Test (TUG), the Tandem Stance Test (TST), a Turkish version of the Stanford Health Assessment Questionnaire (HAQ), and the Beck Depression Inventory (BDI) before and at the end of the treatment. No statistically significant differences were observed between the two groups in terms of the MDS-UPDRS, BBS, TGBA, TST, TUG, HAQ, or BDI measurements before and after the treatment (p > 0.05). Improved balance parameters were observed following balance training in the patients with PD, although static posturography-assisted biofeedback exercises appeared to provide no additional benefit. However, larger, randomized controlled trials are needed to investigate their effectiveness.

Motor speech effects in subthalamic deep brain stimulation for Parkinson's disease.

A motor speech disorder or dysarthria commonly arises in patients with Parkinson's disease (PD). The impact of subthalamic nucleus (STN) deep brain stimulation (DBS) on motor speech and the potential of intraoperative motor speech testing to predict outcomes are unknown. This study examined 1) the types and prevalence of motor speech changes observed with STN DBS and their relation to the preoperative condition, 2) the ability of intraoperative testing to predict postoperative changes in motor speech, and 3) the spatial relationship between stimulation sites producing maximal motor improvement, as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and maximal motor speech deterioration. Comprehensive preoperative, intraoperative, and postoperative motor speech/dysarthria evaluations were performed in consecutive patients with advanced idiopathic PD who underwent STN DBS surgery in the period from 2011 to 2016. Preoperative type of dysarthria and overall dysarthria severity rating along with intraoperative motor speech testing results were evaluated as predictors of postoperative change. Atlas-independent, fully individualized field modeling was used to identify stimulation sites associated with maximal MDS-UPDRS motor improvement and motor speech deterioration. Forty-three patients with PD treated with STN DBS were prospectively studied. Improved MDS-UPDRS motor scores and worsened dysarthria were demonstrated by a subset of patients (16/43). Preoperative dysarthria characteristics did not predict postoperative deterioration. Intraoperative assessment of motor speech strongly predicted postoperative outcomes (OR 4.4, p = 0.02). Sites of maximal MDS-UPDRS motor improvement and worsened dysarthria were distinct. Worsened dysarthria was associated with capsular stimulation, anterior and ventral to the site of maximal MDS-UPDRS motor improvement. The predictive reliability of intraoperative motor speech testing, together with the identification of distinct stimulation sites for motor speech impairment and improved MDS-UPDRS motor function, raise the possibility that DBS lead repositioning or reprogramming could reduce adverse effects on motor speech without impacting MDS-UPDRS motor outcomes in patients undergoing STN DBS.

Dissecting the Domains of Parkinson's Disease: Insights from Longitudinal Item Response Theory Modeling.

Longitudinal item response theory (IRT) models previously suggested that the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor examination has two salient domains, tremor and nontremor, that progress in time and in response to treatment differently. Apply longitudinal IRT modeling, separating tremor and nontremor domains, to reanalyze outcomes in the previously published clinical trial (Study of Urate Elevation in Parkinson's Disease, Phase 3) that showed no overall treatment effects. We applied unidimensional and multidimensional longitudinal IRT models to MDS-UPDRS motor examination items in 298 participants with Parkinson's disease from the Study of Urate Elevation in Parkinson's Disease, Phase 3 (placebo vs. inosine) study. We separated 10 tremor items from 23 nontremor items and used Bayesian inference to estimate progression rates and sensitivity to treatment in overall motor severity and tremor and nontremor domains. The progression rate was faster in the tremor domain than the nontremor domain before levodopa treatment. Inosine treatment had no effect on either domain relative to placebo. Levodopa treatment was associated with greater slowing of progression in the tremor domain than the nontremor domain regardless of inosine exposure. Linear patterns of progression were observed. Despite different domain-specific progression patterns, tremor and nontremor severities at baseline and over time were significantly correlated. Longitudinal IRT analysis is a novel statistical method addressing limitations of traditional linear regression approaches. It is particularly useful because it can simultaneously monitor changes in different, but related, domains over time and in response to treatment interventions. We suggest that in neurological diseases with distinct impairment domains, clinical or anatomical, this application may identify patterns of change unappreciated by standard statistical methods. © 2022 International Parkinson and Movement Disorder Society.

Comparison of Wuqinxi Qigong with Stretching on Single- and Dual-Task Gait, Motor Symptoms and Quality of Life in Parkinson's Disease: A Preliminary Randomized Control Study.

The objective of this study was to investigate the therapeutic effect of Wuqinxi Qigong vs. stretching on single- and dual-task gait, motor symptoms, and quality of life in people with mild and moderate Parkinson’s disease (PD). This single-blind, randomized control trial included 40 participants with idiopathic PD who were randomized into the Wuqinxi Qigong (WQ) group or stretching group. Participants completed 12 weeks (two sessions/week) of intervention. The primary outcomes were gait parameters when performing single-task (comfortable pace) and dual-task (obstacle crossing, serial-3 subtraction and backward digit span) walking, including gait speed, stride length, and double support percentage. The secondary outcomes were ratings from the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), results of the timed-up-and-go test (TUGT), results of the Mini-Balance Evaluation Systems Test (MiniBESTest), and responses from the 39-item Parkinson’s Disease Questionnaire (PDQ-39). All measures were assessed pre- and post-intervention. The WQ group demonstrated increased gait speed (p = 0.000) during the single task, and increased stride length (p = 0.001, p = 0.021) during the single-task and serial-3 subtraction task. Double support percentage significantly decreased (p = 0.004) in the WQ group during the obstacle crossing task, and also decreased (p = 0.045) in the stretching group during the single-task. TUGT (p = 0.005), MiniBESTest (p = 0.023) and PDQ-39 (p = 0.043) in the WQ group significantly improved, and both groups showed significant improvement in MDS-UPDRS after intervention. Wuqinxi Qigong is an effective method to improve single- and dual-task gait. While both exercises improve motor symptoms, Wuqinxi Qigong results in better mobility, balance and quality of life compared to stretching alone.

Resolving Missing Data from the Movement Disorder Society Unified Parkinson's Disease Rating Scale: Implications for Telemedicine.

Telemedicine has become standard in clinical care and research during the coronavirus disease 2019 pandemic. Remote administration of Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III (Motor Examination) precludes ratings of all items, because Rigidity and Postural Stability (six scores) require in-person rating. The objective of this study was to determine imputation accuracy for total-sum and item-specific MDS-UPDRS Motor Examination scores in remote administration. We applied multivariate imputation by chained equations techniques in a cross-sectional dataset where patients had one MDS-UPDRS rating (International Translational Program, n=8,588) and in a longitudinal dataset where patients had multiple ratings (Rush Program, n=396). Successful imputation was stringently defined as (1) generalized Lin's concordance correlation coefficient>0.95, reflecting near-perfect agreement between total-sum score with complete data and surrogate score, calculated without patients' actual Rigidity and Postural Stability scores; and (2) perfect agreement for item-level scores for Rigidity and Postural Stability items. For total-sum score when Rigidity and Postural Stability scores were withdrawn, using one or multiple visits, multivariate imputation by chained equations imputation reached near-perfect agreement with the original total-sum score. However, at the item level, the degree of perfect agreement between the surrogate and actual Rigidity items and Postural Stability scores always fell below threshold. The MDS-UPDRS Part III total-sum score, a key clinical outcome in research and in clinical practice, can be accurately imputed without the Rigidity and Postural Stability items that cannot be rated by telemedicine. No formula, however, allows for specific item-level imputation. When Rigidity and Postural Stability item scores are of key clinical or research interest, patients with PD must be scored in person. © 2022 International Parkinson and Movement Disorder Society.

Cost-effectiveness analysis of the Parkinson’s KinetiGraph and clinical assessment in the management of Parkinson's disease

Aims The Parkinson’s KinetiGraph (PKG) is a wrist-worn movement recording system that collates continuous, objective, data during daily activities in people with Parkinson’s disease (PD) providing a report for clinicians. This study explores the cost-effectiveness of adding the PKG to routine PD assessments. Methods A de novo Markov model of three health states: uncontrolled, controlled and death compared PKG plus routine assessment by a Movement Disease Specialist (MDS) versus routine assessment. Uncontrolled and controlled states were based on the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) II and III scores. The transition between health states was dependent on improvement in MDS-UPDRS II and III, and transition to death state on all cause-mortality and PD-specific relative mortality risk. Markov cycle length was yearly beyond year 1 and lifetime horizon 22 years. Limitations PKG evidence incorporated in this analysis is based on findings from one clinical trial. Health state utilities were mapped and the probability of patients progressing from uncontrolled to controlled health state at the second visit and beyond was derived from a bootstrap method which assumed a normal distribution for MDS-UPDRS. Results The addition of the PKG to usual PD assessments is a cost-effective intervention. PKG plus routine assessment is associated with lower total costs compared to routine assessment (£141,950 versus £159,312) and improved quality-adjusted life years (7.88 versus 7.61), resulting in an incremental cost-effectiveness ratio of −£64,978.99 and a net monetary benefit of £22,706.37 using a £20,000 threshold. Results were robust across sensitivity and scenario analyses. Conclusions Management of PD involves monitoring and evaluation of symptoms to assess disease progression and ensure appropriate treatment choices. Adding the PKG to clinical assessment in routine care allows for improved and objective identification of PD motor symptoms which can be used in clinical decision making to improve patient outcomes.

Abbreviated MDS-UPDRS for Remote Monitoring in PD Identified Using Exhaustive Computational Search

Background The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) comprises 50 items, consisting of historical questions and motor ratings, typically taking around 30 minutes to complete. We sought to identify an abbreviated version that could facilitate use in clinical practice or used remotely via telemedicine. Methods To create an 8-item version we conducted an “exhaustive search” of all possible subsets. We measured explained variance in comparison to the 50-item version using linear regression, with the “optimal” subset maximising this while also meeting remote assessment practicality constraints. The subset was identified using a dataset collected by the Parkinson's Progression Markers Initiative and validated using an MDS Non-Motor Symptoms Scale validation study dataset. Results The optimal remote version comprised items from all parts of the MDS-UPDRS and was found to act as an unbiased estimator of the total 50-item score. This version had an explained variance score of 0.844 and was highly correlated with the total MDS-UPDRS score (Pearson's r = 0.919, p-value <0.0001). Another subset that maximised explained variance score without adhering to remote assessment practicality constraints provided similar results. Conclusion This result demonstrates that the total scores of an abbreviated form identified by computational statistics had high agreement with the MDS-UPDRS total score. Whilst it cannot capture the richness of information of the full MDS-UPDRS, it can be used to create a total score where practicality limits the application of the full MDS-UPDRS, such as remote monitoring. Further validation will be required, including in specific subgroups and advanced disease stages, and full validation of clinimetric properties.

Not just a Snapshot: An Italian Longitudinal Evaluation of Stability of Gut Microbiota Findings in Parkinson’s Disease

Most research analyzed gut-microbiota alterations in Parkinson’s disease (PD) through cross-sectional studies, as single snapshots, without considering the time factor to either confirm methods and findings or observe longitudinal variations. In this study, we introduce the time factor by comparing gut-microbiota composition in 18 PD patients and 13 healthy controls (HC) at baseline and at least 1 year later, also considering PD clinical features. PD patients and HC underwent a fecal sampling at baseline and at a follow-up appointment. Fecal samples underwent sequencing and 16S rRNA amplicons analysis. Patients’clinical features were valued through Hoehn&Yahr (H&Y) staging-scale and Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) Part-III. Results demonstrated stability in microbiota findings in both PD patients and HC over a period of 14 months: both alfa and beta diversity were maintained in PD patients and HC over the observation period. In addition, differences in microbiota composition between PD patients and HC remained stable over the time period. Moreover, during the same period, patients did not experience any worsening of either staging or motor impairment. Our findings, highlighting the stability and reproducibility of the method, correlate clinical and microbiota stability over time and open the scenario to more extensive longitudinal evaluations.

Short chain fatty acids-producing and mucin-degrading intestinal bacteria predict the progression of early Parkinson’s disease

To elucidate the relevance of gut dysbiosis in Parkinson’s disease (PD) in disease progression, we made random forest models to predict the progression of PD in two years by gut microbiota in 165 PD patients. The area under the receiver operating characteristic curves (AUROCs) of gut microbiota-based models for Hoehn & Yahr (HY) stages 1 and 2 were 0.799 and 0.705, respectively. Similarly, gut microbiota predicted the progression of Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III scores in an early stage of PD with AUROC = 0.728. Decreases of short-chain fatty acid-producing genera, Fusicatenibacter, Faecalibacterium, and Blautia, as well as an increase of mucin-degrading genus Akkermansia, predicted accelerated disease progression. The four genera remained unchanged in two years in PD, indicating that the taxonomic changes were not the consequences of disease progression. PD patients with marked gut dysbiosis may thus be destined to progress faster than those without gut dysbiosis.

Alteration of Gut Microbial Metabolites in the Systemic Circulation of Patients with Parkinson's Disease.

Emerging evidence suggests that gut dysbiosis contributes to Parkinson's disease (PD) by signaling through microbial metabolites. Hippuric acid (HA), indole derivatives, and secondary bile acids are among the most common gut metabolites. To examine the relationship of systemic concentrations of these microbial metabolites associated with changes of gut microbiota, PD status, and severity of PD. We enrolled 56 patients with PD and 43 age- and sex-matched healthy participants. Motor and cognitive severity were assessed with Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III motor score and the Mini-Mental State Examination (MMSE), respectively. Plasma concentrations of targeted gut metabolites were measured with liquid chromatography-tandem mass spectrometry. Gut microbiota was analyzed with shotgun metagenomic sequencing. Compared with controls, PD patients had significantly higher plasma levels of HA, indole-3-propionic acid (IPA), deoxycholic acid (DCA), and glycodeoxycholic acid (GDCA). After adjustment for age and sex in a multivariate logistic regression analysis, plasma levels of HA (odds ratio [OR] 3.21, p < 0.001), IPA (OR 2.59, p = 0.031), and GDCA (OR 2.82, p = 0.036) were associated with positive PD status. Concentrations of these gut metabolites did not correlate with MDS-UPDRS part III score or MMSE after adjustment for confounders. Microbial metabolite levels were associated with the relative abundance of pro-inflammatory gut bacteria. Aberrant gut microbial metabolites of HA, indole derivatives and secondary bile acids associated with specific gut microbiota changes were observed in patients with PD.

Unilateral GPi-DBS Improves Ipsilateral and Axial Motor Symptoms in Parkinson's Disease as Evidenced by a Brain Perfusion Single Photon Emission Computed Tomography Study.

IntroductionDeep brain stimulation (DBS) is an effective treatment for advanced Parkinson’s disease (PD) with the targeting bilateral subthalamic nucleus or globus pallidus internus (STN or GPi-DBS). So far, detailed studies on the efficacy of unilateral STN-DBS for motor symptoms have been reported, but few studies have been conducted on unilateral GPi-DBS.Materials and MethodsSeventeen patients with Parkinson’s disease (PwPD) who underwent unilateral GPi-DBS were selected. We conducted comparison analyses between scores obtained 6–42 months pre- and postoperatively using the following measurement tools: the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III, the Hoehn and Yahr stage, the presence/absence of dyskinesia, Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), Geriatric Depression Scale (GDS), levodopa equivalent dose (LED), and cerebral blood flow by single photon emission computed tomography (SPECT). Patient backgrounds were compared between four cohorts with favorable (good responders, ≥50% improvement) and unfavorable (poor responders, <50% improvement) postoperative outcome.ResultsSignificant improvement was observed postoperatively in the following: total MDS-UPDRS Part III scores during the off period, contralateral scores, ipsilateral scores, and axial scores. Similarly, the Hoehn and Yahr stages during the off period, and GDS also showed significant decrease. In contrast, LED, MMSE, and FAB remained unchanged while the number of patients who scored positive for dyskinesia decreased by 40%. Abnormal cerebral blood flow preoperatively seen in the cerebral cortex had normalized in the total score-based good responder cohort. In the ipsilateral score-based good responder cohort, cerebral blood flow increased in the contralateral frontal lobe including in the premotor cortex, contralateral to the DBS. Compared to the poor responders, postoperative good responders demonstrated significantly higher preoperative MMSE scores.DiscussionUnilateral GPi-DBS therapy was effective in improving contralateral, ipsilateral, and axial motor symptoms of patients with advanced PD; in particular, it was found to be especially beneficial in PwPD whose cognitive function was unimpaired; the treatment efficacy rivaled that of bilateral counterparts up till at least 6 months postoperatively. Finally, normalization of preoperative abnormalities in cerebral blood flow and increased cerebral blood flow in the contralateral frontal lobe indicated the beneficial potential of this therapy on ipsilateral motor symptoms.

Elevated α-synuclein and NfL levels in tear fluids and decreased retinal microvascular densities in patients with Parkinson's disease.

The pathognomonic hallmark of Parkinson's disease (PD), α-synuclein, has been observed in the retina of PD patients. We investigated whether biomarkers in the tears and retinal microvascular changes associate with PD risk and progression. This prospective study enrolled 49 PD patients and 45 age-matched healthy controls. The α-synuclein and neurofilament light chain (NfL) levels were measured using an electrochemiluminescence immunoassay. Retinal vessel density was assessed using optical coherence tomography angiography (OCT-A). The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Mini-Mental State Examination score were used to assess motor and cognitive progression. The α-synuclein and NfL levels in the tears were higher in PD patients than in controls (α-synuclein: 55.49 ± 8.12pg/mL vs. 31.71 ± 3.25pg/mL, P = 0.009; NfL: 2.89 ± 0.52pg/mL vs. 1.47 ± 0.23pg/mL, P = 0.02). The vessel densities in the deep plexus of central macula and the radial peripapillary capillary layer of disc region were lower in PD patients with moderate-stage compared with early-stage PD (P < 0.05). The accuracy of predicting PD occurrence using age and sex alone (area under the curve [AUC] 0.612) was significantly improved by adding α-synuclein and NfL levels and retinal vascular densities (AUC 0.752, P = 0.001). After a mean follow-up of 1.5 ± 0.3years, the accuracy of predicting motor or cognitive progression using age, sex, and baseline motor severity as a basic model was increased by incorporating retinal microvascular and biofluid markers as a full model (P = 0.001). Our results showed that retinal microvascular densities combined with α-synuclein and NfL levels in tears are associated with risk and progression of PD.

Intraoperative Quantification of MDS-UPDRS Tremor Measurements Using 3D Accelerometry: A Pilot Study.

The most frequently used method for evaluating tremor in Parkinson’s disease (PD) is currently the internationally standardized Movement Disorder Society—Unified PD Rating Scale (MDS-UPDRS). However, the MDS-UPDRS is associated with limitations, such as its inherent subjectivity and reliance on experienced raters. Objective motor measurements using accelerometry may overcome the shortcomings of visually scored scales. Therefore, the current study focuses on translating the MDS-UPDRS tremor tests into an objective scoring method using 3D accelerometry. An algorithm to measure and classify tremor according to MDS-UPDRS criteria is proposed. For this study, 28 PD patients undergoing neurosurgical treatment and 26 healthy control subjects were included. Both groups underwent MDS-UPDRS tests to rate tremor severity, while accelerometric measurements were performed at the index fingers. All measurements were performed in an off-medication state. Quantitative measures were calculated from the 3D acceleration data, such as tremor amplitude and area-under-the-curve of power in the 4–6 Hz range. Agreement between MDS-UPDRS tremor scores and objective accelerometric scores was investigated. The trends were consistent with the logarithmic relationship between tremor amplitude and MDS-UPDRS score reported in previous studies. The accelerometric scores showed a substantial concordance (>69.6%) with the MDS-UPDRS ratings. However, accelerometric kinetic tremor measures poorly associated with the given MDS-UPDRS scores (R2 < 0.3), mainly due to the noise between 4 and 6 Hz found in the healthy controls. This study shows that MDS-UDPRS tremor tests can be translated to objective accelerometric measurements. However, discrepancies were found between accelerometric kinetic tremor measures and MDS-UDPRS ratings. This technology has the potential to reduce rater dependency of MDS-UPDRS measurements and allow more objective intraoperative monitoring of tremor.

Physical Activity and Its Diurnal Fluctuations Vary by Non-Motor Symptoms in Patients with Parkinson's Disease: An Exploratory Study.

Background: This exploratory study investigated the association between non-motor symptoms (NMS) and both physical activity and diurnal activity patterns in patients with Parkinson’s disease (PwPD). Methods: Participants included PwPD with modified Hoehn and Yahr stages 1–3. The presence of NMS was assessed with Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part I. Physical activity was measured using a waist-mounted triaxial accelerometer. Logistic regression analyses evaluated associations between NMS and physical activity; furthermore, diurnal fluctuation in physical activity due to NMS was examined by ANCOVA. Results: Forty-five PwPD were included in the study. Among the domains of NMS, pain and other sensations (OR, 8.36; 95% CI, 1.59–43.94) and fatigue (OR, 14.26; 95% CI, 1.85–109.90) were associated with low daily step count (<4200 steps/day). Analysis by time of day showed no characteristic variability in physical activity but had constant effect sizes for pain and other sensations (p = 0.20, ES = 0.36) and fatigue (p = 0.08, ES = 0.38). Conclusion: Our exploratory study suggested that PwPD with pain and other sensations and fatigue recorded lower step counts than their asymptomatic counterparts. Therefore, PwPD with pain and fatigue may need more support in promoting physical activity.