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

Reliability and validity of Japanese version of Unified Multiple System Atrophy Rating Scale

AbstractBackground/AimThe Unified Multiple System Atrophy Rating Scale (UMSARS) has been broadly used to assess the progression of multiple system atrophy (MSA). In this study, we translated UMSARS into Japanese and tested the reliability and validity of the translated version for the assessment of Japanese patients with MSA.MethodUMSARS was translated into Japanese. For the evaluation of the reliability of the translated version, 60 and 70 participants with MSA were assessed by two neurologists using the Japanese versions of UMSARS‐I and UMSARS‐II, respectively. For the validation, 70 participants with MSA were evaluated by one neurologist using the Japanese versions of UMSARS‐I and UMSARS‐II, and other scales. Cronbach's alpha coefficient, Cohen's kappa coefficient [κ (w)], and Spearman rank correlation were calculated.ResultsCronbach's alpha coefficients of the Japanese versions of UMSARS‐I and UMSARS‐II were 0.87 and 0.90, respectively. The κ (w) values of UMSARS‐I and UMSARS‐II items were 0.61‐0.81 and 0.51‐0.86, respectively. The total UMSARS‐I score correlated well with the scores of Barthel Index, Schwab and England Activities of Daily Living Scale, Functional Independence Measure, and Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) part 2 (Spearman rank correlations, −0.75, −0.71, −0.82, and 0.81, respectively). The total UMSARS‐II score correlated well with the scores of International Cooperative Ataxia Rating Scale and MDS‐UPDRS part 3 (Spearman rank correlations, 0.85 and 0.86, respectively).ConclusionsThe Japanese version of UMSARS is reliable and valid for the assessment of the clinical severity of MSA in Japan.

The 3-Item "Apathy" Subscale Within the GDS-15 Is Not Supported in De Novo Parkinson's Disease Patients: Analysis of the PPMI Cohort.

This study examined individual components of the Geriatric Depression Scale-15 (GDS-15) to determine whether the 3-item Withdrawal-Apathy-Lack of Vigor (WAV) subscale, which has been validated in older adults and advanced Parkinson's disease (PD), was applicable to newly diagnosed patients with PD. Baseline Parkinson's Progression Markers Initiative (PPMI) data (n = 345), including GDS-15 and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) depression, apathy, and anxiety scores, were examined. Data reduction techniques (i.e., principal components, confirmatory factor analyses) were used. Model fit was poor for the previously identified GDS-15 factor structures. Via principal components analysis, 5 components were identified, none of which reflected the 3-item WAV subscale previously reported in the literature. Internal consistency of the GDS-15 was acceptable, as was the internal consistency for the largest component (labeled "Dysphoria"). All 5 components significantly correlated with the MDS-UPDRS depression, apathy, and anxiety items. Model fit was fair for the "Dysphoria" factor only. Overall, the 3-item WAV factor reported in previous literature was not supported in this sample of de novo PD patients.

A Double-Blind, Randomized, Controlled Trial of Lovastatin in Early-Stage Parkinson's Disease.

Recent evidence indicates that lipophilic statins have a neuroprotective benefit in animal models of Parkinson's disease (PD). The objective of this study was to evaluate whether lovastatin has the potential to slow motor symptom progression in patients with early-stage PD. This double-blind, randomized, placebo-controlled trial enrolled 77 patients with early-stage PD between May 23, 2017, and July 12, 2018, with follow-up ending September 1, 2019. Lovastatin 80 mg/day or placebo with 1:1 randomization was administered for 48 weeks. Mean change in the parts I-III scores of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), changes in the striatal dopamine uptake ratio measured by 18 F-dopa PET scan, and changes in PD medications between baseline and the week 48 visit were measured. Of the 77 randomized patients, 70 (90.9%) completed the study. There was a slightly beneficial trend of the MDS-UPDRS motor score in the lovastatin group (-3.18± 5.50) compared with the placebo group (-0.50 ± 6.11); P=0.14 adjusted for age, sex, disease duration, and baseline LEDD. Mean percentage change in the striatal 18 F-dopa uptake ratio deteriorated less in the lovastatin group than in the placebo group on the dominant side of caudate (1.2% ± 7.3% vs -7.1% ± 8.2%, P < 0.01) and putamen (2.3% ± 7.1% vs -6.4% ± 8.1%, P < 0.01). We found no between-group differences in the change in part I or part II MDS-UPDRS scores. Lovastatin was generally well tolerated. Lovastatin treatment in patients with early-stage PD was associated with a trend of less motor symptom worsening and was well tolerated. A future larger long-term follow-up study is needed to confirm our findings. © 2021 International Parkinson and Movement Disorder Society.

Exploring Movement Impairments in Patients With Parkinson's Disease Using the Microsoft Kinect Sensor: A Feasibility Study.

Background: Current assessments of motor symptoms in Parkinson's disease are often limited to clinical rating scales.Objectives: To develop a computer application using the Microsoft Kinect sensor to assess performance-related bradykinesia.Methods: The developed application (Motorgame) was tested in patients with Parkinson's disease and healthy controls. Participants were assessed with the Movement Disorder Society Unified Parkinson's disease Rating Scale (MDS-UPDRS) and standardized clinical side effect rating scales, i.e., UKU Side Effect Rating Scale and Simpson-Angus Scale. Additionally, tests of information processing (Symbol Coding Task) and motor speed (Token Motor Task), together with a questionnaire, were applied.Results: Thirty patients with Parkinson's disease and 33 healthy controls were assessed. In the patient group, there was a statistically significant (p < 0.05) association between prolonged time of motor performance in the Motorgame and upper body rigidity and bradykinesia (MDS-UPDRS) with the strongest effects in the right hand (p < 0.001). In the entire group, prolonged time of motor performance was significantly associated with higher Simson-Angus scale rigidity score and higher UKU hypokinesia scores (p < 0.05). A shortened time of motor performance was significantly associated with higher scores on information processing (p < 0.05). Time of motor performance was not significantly associated with Token Motor Task, duration of illness, or hours of daily physical activity. The Motorgame was well-accepted.Conclusions: In the present feasibility study the Motorgame was able to detect common motor symptoms in Parkinson's disease in a statistically significant and clinically meaningful way, making it applicable for further testing in larger samples.

Outcome of Deep Brain Stimulation (DBS) for the Treatment of Parkinson’s Disease in Terms of Improvement in MDS-UPDRS Scale Over 5 Years

Background &amp; Objective: Parkinson’s disease (PD) is the second most common Neurodegenerative disorder after Alzheimer’s disease. There are several surgical procedures for advanced PD, but amongst all deep brain stimulation has proven to be safest and effective. The objective of this study was to see the outcome of DBS for the treatment of PD in terms of improvement in MDS UPDRS over 5 years.&#x0D; Material and Methods: 44 patients were included in study from Oct 2014 to Sep 2019. History, examination was carried out, and preoperative MDS-UPDRS (Movement Disorder Society Unified Parkinson’s Disease Rating Scale) was recorded. Postoperative improvement in MDS-UPDRS score was assessed at first Programming, 2nd week, and 6th week and at 3rd month.&#x0D; Results: At baseline the mean, the MDS – UPDRS (Part-I) score was 14.20 ± 0.61 and at the end of 3rd month, the mean score was 11.18 ± 0.47 respectively. At baseline the mean, the MDS – UPDRS (part-II) score was 18.99 ± 0.70 and at the end of 3rd month, the mean score was 13.01 ± 0.57, respectively. At baseline the mean, the MDS – UPDRS (part-III) score was 45.19 ± 0.90 and at the end of 3rd month, the mean score was 25.15 ± 1.20 respectively. At baseline the mean, the MDS – UPDRS (part-IV) score was 10.18 ± 0.87 and at the end of 3rd month, the mean score was 3.85 ± 1.03, respectively. &#x0D; Conclusion: The Deep Brain Stimulation (DBS) is safe and effective in the management of PD.

Modeling long-term health and economic implications of new treatment strategies for Parkinson’s disease: an individual patient simulation study

ABSTRACT Background: Simulation modeling facilitates the estimation of long-term health and economic outcomes to inform healthcare decision-making. Objective: To develop a framework to simulate progression of Parkinson’s disease (PD), capturing motor and non-motor symptoms, clinical outcomes, and associated costs over a lifetime. Methods: A patient-level simulation was implemented accounting for individual variability and interrelated changes in common disease progression scales. Predictive equations were developed to model progression for newly diagnosed patients and were combined with additional sources to inform long-term progression. Analyses compared a hypothetical disease-modifying therapy (DMT) with a standard of care to explore the drivers of cost-effectiveness. Results: The equations captured the dependence between the various measures, leveraging prior values and rates of change to obtain realistic predictions. The simulation was built upon several interrelated equations, validated by comparison with observed values for the Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) and UPDRS subscales over time. In a case study, disease progression rates, patient utilities, and direct non-medical costs were drivers of cost-effectiveness. Conclusions: The developed equations supported the simulation of early PD. This model can support conducting simulations to inform internal decision-making, trial design, and strategic planning early in the development of new DMTs entering clinical trials.

Six-Month Community-Based Brisk Walking and Balance Exercise Alleviates Motor Symptoms and Promotes Functions in People with Parkinson's Disease: A Randomized Controlled Trial.

In Parkinson's disease (PD), sustained aerobic exercise is a promising therapy in delaying motor disability. Brisk walking is a moderate intensity aerobic training, which could be translated to community practice at low cost, but its effects on motor symptoms remains unclear. To determine the effectiveness of a six-month brisk walking and balance program in alleviating motor symptoms, and promoting functional, gait, and balance performance in people with PD. Seventy individuals with mild to moderate PD were randomly assigned to a brisk walking (BW) group or an active control (CON) group. BW group received ten 90-minute supervised brisk walking and balance exercise for six months (weeks 1-6: once/week, weeks 7-26: once/month). CON group received upper limb training. Both groups performed 2-3 self-practice sessions weekly. Primary outcome was Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score. Secondary outcomes were fast gait speed (FGS), timed-up-and-go (TUG) time, six-minute walk distance (6MWD), and Mini-Balance Evaluation Systems Test (Mini-BEST) score. Sixty-four participants (33 BW/31 CON) completed training. BW group showed greater significant decreases from baseline than CON group in MDS-UPDRS motor score after six weeks (-5.5 vs -1.6, p < 0.001) and 6 months (-6.0 vs -1.4, p < 0.001) of training. BW group also showed greater significant improvement from the baseline than CON group for TUG time, FGS, 6MWD, and mini-BEST score (all p < 0.05). The six-month brisk walking and balance program alleviates motor symptoms, promotes functional and gait performance, walking capacity, and dynamic balance in people with mild to moderate PD.

Table tennis for patients with Parkinson’s disease: A single-center, prospective pilot study

IntroductionTable tennis is a popular sport worldwide. However, no study has examined whether it is an effective exercise for patients with Parkinson’s disease (PD). The efficacy and safety of table tennis exercise for PD patients was examined. MethodsThis 6-month prospective study investigated if our table tennis exercise program could improve parkinsonian motor symptoms, cognition and psychiatric symptoms. Twelve PD patients with Hoehn & Yahr stage ≤4 were recruited. Patients participated in a 6-hour exercise session once weekly. All patients were assessed with the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) parts I-IV, Montreal Cognitive Assessment (MoCA), Frontal Assessment Battery (FAB), Self-Rating Depression Scale (SDS), and Starkstein Apathy Scale (SAS) at baseline, 3 months, and 6 months. ResultsNine of 12 PD patients were analyzed, except for three patients for which data was missing. MDS-UPDRS parts II and III were improved at 3 months (median −4.0, p = 0.012 and median −10.0, p = 0.012) and 6 months (median −7.0, p = 0.015 and median −12.0, p = 0.008), whereas MDS-UPDRS total parts I scores and total IV scores, MoCA, FAB, SDS, and SAS were unchanged. Adverse events included fall and backache in one patient each. ConclusionA table tennis exercise program is relatively safe and may improve activities of daily living and motor symptoms in patients with PD.

Randomized Trial of Focused Ultrasound Subthalamotomy for Parkinson’s Disease

BackgroundThe subthalamic nucleus is the preferred neurosurgical target for deep-brain stimulation to treat cardinal motor features of Parkinson’s disease. Focused ultrasound is an imaging-guided method for creating therapeutic lesions in deep-brain structures, including the subthalamic nucleus.MethodsWe randomly assigned, in a 2:1 ratio, patients with markedly asymmetric Parkinson’s disease who had motor signs not fully controlled by medication or who were ineligible for deep-brain stimulation surgery to undergo focused ultrasound subthalamotomy on the side opposite their main motor signs or a sham procedure. The primary efficacy outcome was the between-group difference in the change from baseline to 4 months in the Movement Disorder Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) motor score (i.e., part III) for the more affected body side (range, 0 to 44, with higher scores indicating worse parkinsonism) in the off-medication state. The primary safety outcome (procedure-related complications) was assessed at 4 months.ResultsAmong 40 enrolled patients, 27 were assigned to focused ultrasound subthalamotomy (active treatment) and 13 to the sham procedure (control). The mean MDS-UPDRS III score for the more affected side decreased from 19.9 at baseline to 9.9 at 4 months in the active-treatment group (least-squares mean difference, 9.8 points; 95% confidence interval [CI], 8.6 to 11.1) and from 18.7 to 17.1 in the control group (least-squares mean difference, 1.7 points; 95% CI, 0.0 to 3.5); the between-group difference was 8.1 points (95% CI, 6.0 to 10.3; P<0.001). Adverse events in the active-treatment group were dyskinesia in the off-medication state in 6 patients and in the on-medication state in 6, which persisted in 3 and 1, respectively, at 4 months; weakness on the treated side in 5 patients, which persisted in 2 at 4 months; speech disturbance in 15 patients, which persisted in 3 at 4 months; facial weakness in 3 patients, which persisted in 1 at 4 months; and gait disturbance in 13 patients, which persisted in 2 at 4 months. In 6 patients in the active-treatment group, some of these deficits were present at 12 months.ConclusionsFocused ultrasound subthalamotomy in one hemisphere improved motor features of Parkinson’s disease in selected patients with asymmetric signs. Adverse events included speech and gait disturbances, weakness on the treated side, and dyskinesia. (Funded by Insightec and others; ClinicalTrials.gov number, NCT03454425.)

Zuranolone as an oral adjunct to treatment of Parkinsonian tremor: A phase 2, open-label study

Parkinson's disease (PD) is characterized by both motor and nonmotor deficits. Among cardinal symptoms of this disorder, tremor is the least responsive to dopamine replacement therapy and is often undertreated. Zuranolone (SAGE-217) is an investigational oral neuroactive steroid (NAS) gamma-aminobutyric acid A (GABAA) receptor–positive allosteric modulator (PAM) that has been investigated for its safety and efficacy in patients with PD. In the current open-label study, zuranolone capsules (20 to 30 mg) were administered for 7 days in 14 patients (mean age, 65.1 years; mean time since PD diagnosis, 9 years). The primary efficacy endpoint was reduction in tremor symptoms, as assessed by change from baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part II/III Tremor Scores on Day 8. Additional endpoints included improvements in overall motor symptoms, and motor and nonmotor aspects of daily living. Adverse events (AEs) were also monitored. The MDS-UPDRS Part II/III Tremor Score improved by 40% (P < 0.0001) from baseline on Day 8. The motor score, and nonmotor experiences of daily living (nM-EDL), and motor experiences of daily living (m-EDL) scores (MDS-UPDRS Parts I and II, respectively), also improved on Day 8. No serious AEs were reported, and no patients discontinued treatment. The most common AEs were dizziness, sedation, and somnolence. Zuranolone was generally well tolerated and improved tremor symptoms in patients with PD who were on stable doses of concurrent dopaminergic agents. These data support the further investigation of NAS GABAA receptor PAMs as adjunctive treatments for tremor in patients with PD.

Changes in Motor, Cognitive, and Behavioral Symptoms in Parkinson's Disease and Mild Cognitive Impairment During the COVID-19 Lockdown.

Objective: The effects of the COVID-19 lockdown on subjects with prodromal phases of dementia are unknown. The aim of this study was to evaluate the motor, cognitive, and behavioral changes during the COVID-19 lockdown in Italy in patients with Parkinson's disease (PD) with and without mild cognitive impairment (PD-MCI and PD-NC) and in patients with MCI not associated with PD (MCInoPD).Methods: A total of 34 patients with PD-NC, 31 PD-MCI, and 31 MCInoPD and their caregivers were interviewed 10 weeks after the COVID-19 lockdown in Italy, and changes in cognitive, behavioral, and motor symptoms were examined. Modified standardized scales, including the Neuropsychiatric Inventory (NPI) and the Movement Disorder Society, Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I and II, were administered. Multivariate logistic regression was used to evaluate associated covariates by comparing PD-NC vs. PD-MCI and MCInoPD vs. PD-MCI.Results: All groups showed a worsening of cognitive (39.6%), pre-existing (37.5%), and new (26%) behavioral symptoms, and motor symptoms (35.4%) during the COVID-19 lockdown, resulting in an increased caregiver burden in 26% of cases. After multivariate analysis, PD-MCI was significantly and positively associated with the IADL lost during quarantine (OR 3.9, CI 1.61–9.58), when compared to PD-NC. In the analysis of MCInoPD vs. PD-MCI, the latter showed a statistically significant worsening of motor symptoms than MCInoPD (OR 7.4, CI 1.09–45.44). Regarding NPI items, nighttime behaviors statistically differed in MCInoPD vs. PD-MCI (16.1% vs. 48.4%, p = 0.007). MDS-UPDRS parts I and II revealed that PD-MCI showed a significantly higher frequency of cognitive impairment (p = 0.034), fatigue (p = 0.036), and speech (p = 0.013) than PD-NC. On the contrary, PD-MCI showed significantly higher frequencies in several MDS-UPDRS items compared to MCInoPD, particularly regarding pain (p = 0.001), turning in bed (p = 0.006), getting out of bed (p = 0.001), and walking and balance (p = 0.003).Conclusion: The COVID-19 quarantine is associated with the worsening of cognitive, behavioral, and motor symptoms in subjects with PD and MCI, particularly in PD-MCI. There is a need to implement specific strategies to contain the effects of quarantine in patients with PD and cognitive impairment and their caregivers.

Determinants and impact of alexithymia on quality of life in Parkinson's disease

IntroductionAlexithymia is a neuropsychiatric symptom conceptualized as difficulty identifying and describing feelings. Although associated with other non-motor symptoms, mainly neuropsychiatric, alexithymia may present as an isolated symptom in persons with Parkinson's Disease (PwP). The objective of the study is to identify determinants of alexithymia and its association with quality of life (QoL) in Parkinson's disease. MethodsSubjects with Parkinson's disease were recruited. The following instruments were applied: Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Non-Motor Symptoms Scale (NMSS), Montreal Cognitive Assessment (MoCA), Toronto alexithymia scale (TAS-20) and Parkinson's Disease Questionnaire (PDQ-8). Matched healthy controls were screened using TAS-20. Clinical and demographical variables were compared between alexithymic and non-alexithymic. Regression models were used to find determinants of alexithymia. Impact of alexithymia on QoL was estimated with a linear regression model. Results98 patients were included. 56.1% PwP and 28.8% controls were alexithymic (p<0.001). Education level (OR 0.86) and NMSS urinary score (OR 1.09) determined alexithymia as well as TAS-20 score. Alexithymia was an independent determinant of QoL. ConclusionsAlexithymia is a prevalent independent non-motor symptom in PwP with impact on QoL. Low education level and urinary symptoms are important determinants of alexithymia.

Efficacy of short-term multidisciplinary intensive rehabilitation in patients with different Parkinson's disease motor subtypes: a prospective pilot study with 3-month follow-up.

Parkinson's disease (PD) can be classified into three motor-based subtypes: postural instability/gait difficulty (PIGD), tremor dominant (TD), and indeterminate. The neuropathophysiological mechanisms of the three motor subtypes are different, which may lead to different responses to therapy. Sixty-nine patients with idiopathic Parkinson's disease (Hoehn-Yahr stage ≤ 3) were screened from 436 patients with Parkinsonism recruited through outpatient services and the internet. According to the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) TD/PIGD ratio, the patients were divided into PIGD (TD/PIGD ≤ 0.09; n = 36), TD (TD/PIGD ≥1.15; n = 19), and indeterminate (TD/PIGD = 0.90-1.15; n = 14) groups. All patients received 2 weeks of multidisciplinary intensive rehabilitation treatment (MIRT) during hospitalization, as well as a remote home rehabilitation health education class. Compared with the scores at admission, all patients showed significant improvements in their MDS-UPDRS III score, walking ability, balance, and posture control at discharge. Moreover, the MDS-UPDRS III score improvement was greater in the PIGD group than in the TD group. The follow-up data, collected for 3 months after discharge, showed that overall symptom improvement in each group was maintained for 1-3 months. Furthermore, there were no significant differences in the duration or grade effects of symptom improvement among the three groups. These findings suggest that 2 weeks of MIRT is effective for improving motor performance in all three motor subtypes. Patients in the PIGD group had a better response after hospitalization than those in the TD group. This study was approved by the Institutional Ethics Committee of Beijing Rehabilitation Hospital of Capital Medical University of China (approval No. 2018bkky022) on May 7, 2018 and registered with the Chinese Clinical Trial Registry (registration No. ChiCTR1900020771) on January 19, 2019.

PND2 Indirect Treatment Comparisons of Apomorphine Sublingual Film Versus Apomorphine Subcutaneous Injection for the on-Demand Treatment of "Off" Episodes in Patients with Parkinson's Disease

To conduct an indirect treatment comparison (ITC) of 2 approved routes of apomorphine administration for the on-demand treatment of “OFF” episodes in patients with Parkinson’s disease (PD): apomorphine sublingual film (APL-130277; APL) and apomorphine subcutaneous injection (apo-SC). A systematic literature review was conducted and updated until 20May2020 to identify relevant randomized controlled trials. Eight studies were identified, which varied in design (eg, duration, placebo arm, assessment methods, etc). Outcomes included: (1) change from baseline in Part III score of Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) for APL or UPDRS for apo-SC, (2) mean reduction in “OFF” time (determined by patient-reported “OFF”/FULL “ON” status at discrete timepoints between 0–90 minutes for APL or by mean number of treated “OFF” episodes/day multiplied by mean reduction in “OFF” time/episode due to therapy as reported in patient diaries for apo-SC), and (3) the proportion of patients who turned FULLY “ON” (for APL) or “ON” (for apo-SC) based on patient diaries. ITC feasibility was assessed based on data availability and heterogeneity across studies. Apo-SC had a more favorable mean change in UPDRS Part III score at 20 minutes postdose vs APL in MDS-UPDRS Part III score at 30 minutes postdose (mean difference [95% credible interval], –12.4 [–17.2, –7.6]), APL and apo-SC had similar response estimates at 60 minutes postdose (–0.5 [–8.0, 7.0]), and APL had a more favorable response estimate vs apo-SC at 90 minutes postdose (–8.2 [–15.0, –1.4]). APL and apo-SC had a similar estimated mean reduction in “OFF” time (mean difference [95% credible interval], 4.38 minutes [–7.5, 16.2]). Data limitations prevented ITCs for the proportion of patients who turned FULLY “ON”/“ON.” ITCs suggest that APL may provide comparable efficacy to apo-SC, therefore other factors, such as route of administration, may influence specific treatment decisions.

Comparing Objective and Subjective Measures of Parkinson's Disease Using the Parkinson's KinetiGraph.

Background: Parkinson's disease (PD) is a neurodegenerative disease that can lead to impaired motor function and execution of activities of daily living (ADL). Since clinicians typically can only observe patients' symptoms during visits, prescribed medication schedules may not reflect the full range of symptoms experienced throughout the day. Therefore, objective tools are needed to provide comprehensive symptom data to optimize treatment. One such tool is the Parkinson's KinetiGraph® (PKG), a wearable sensor that measures motor symptoms of Parkinson's disease.Objective: To build a mathematical model to determine if PKG data measuring Parkinson's patients' motor symptoms can predict patients' ADL impairment.Methods: Thirty-four patients with PD wore the PKG device for 6 days while performing their ADL. Patients' PKG scores for bradykinesia and dyskinesia, as well as their responses to a questionnaire asking if their ADL-level had been impacted by various motor symptoms, were used to build a multiple regression model predicting the patients' Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part II scores.Results: Calculation of bradykinesia score response to medication showed that using a dosage response time of 30 min yielded a greater bradykinesia response than when the response time was set to 40, 50, 60, 70, 80, or 90 min. The overall multiple regression model predicting MDS-UPDRS part II score was significant (R2 = 0.546, p < 0.001).Conclusion: The PKG's ability to provide motor symptom data that correlates with clinical measures of ADL impairment suggests that it has strong potential as a tool for the assessment and management of Parkinson's disease motor symptoms.

Validation of the Polish version of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS).

In 2008, the Movement Disorders Society (MDS) published a new Unified Parkinson's Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson's Disease (PD). We have translated and validated the Polish version of the MDS-UPDRS, explored its dimensionality, and compared it to the original English one. The MDS-UPDRS was translated into Polish by a team of Polish investigators led by JS and GO. The back-translation was completed by colleagues fluent in both languages (Polish and English) who were not involved in the original translation, and was reviewed by members of the MDS Rating Scales Programme. Then the translated version of the MDS-UPDRS underwent cognitive pretesting, and the translation was modified based on the results. The final translation was approved as the Official Working Document of the MDS-UPDRS Polish version, and was tested on 355 Polish PD patients recruited at movement disorders centres all over Poland (at Katowice, Gdańsk, Łódź, Warsaw, Wrocław, and Kraków). Confirmatory and explanatory factor analyses were applied to determine whether the factor structure of the English version could be confirmed in the Polish version. The Polish version of the MDS-UPDRS showed satisfactory clinimetric properties. The internal consistency of the Polish version was satisfactory. In the confirmatory factor analysis, all four parts had greater than 0.90 comparative fit index (CFI) compared to the original English MDS-UPDRS. Explanatory factor analysis suggested that the Polish version differed from the English version only within an acceptable range. The Polish version of the MDS-UPDRS meets the requirements to be designated as the Official Polish Version of the MDS-UPDRS, and is available on the MDS web page. We strongly recommend using the MDS-UPDRS instead of the UPDRS for research purposes and in everyday clinical practice.

Estimating the Effect of Early Treatment Initiation in Parkinson's Disease Using Observational Data.

ABSTRACTBackgroundBoth patients and physicians may choose to delay initiation of dopamine replacement therapy in Parkinson's disease (PD) for various reasons. We used observational data to estimate the effect of earlier treatment in PD. Observational data offer a valuable source of evidence, complementary to controlled trials.MethodWe studied the Parkinson's Progression Markers Initiative cohort of patients with de novo PD to estimate the effects of duration of PD treatment during the first 2 years of follow‐up, exploiting natural interindividual variation in the time to start first treatment. We estimated the Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part III (primary outcome) and several functionally relevant outcomes at 2, 3, and 4 years after baseline. To adjust for time‐varying confounding, we used marginal structural models with inverse probability of treatment weighting and the parametric g‐formula.ResultsWe included 302 patients from the Parkinson's Progression Markers Initiative cohort. There was a small improvement in MDS‐UPDRS Part III scores after 2 years of follow‐up for patients who started treatment earlier, and similar, but nonstatistically significant, differences in subsequent years. We found no statistically significant differences in most secondary outcomes, including the presence of motor fluctuations, nonmotor symptoms, MDS‐UPDRS Part II scores, and the Schwab and England Activities of Daily Living Scale.ConclusionEarlier treatment initiation does not lead to worse MDS‐UPDRS motor scores and may offer small improvements. These findings, based on observational data, are in line with earlier findings from clinical trials. Observational data, when combined with appropriate causal methods, are a valuable source of additional evidence to support real‐world clinical decisions. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Kinematic but not clinical measures predict falls in Parkinson-related orthostatic hypotension.

We sought to test the hypothesis that technology could predict the risk of falls in Parkinson's disease (PD) patients with orthostatic hypotension (OH) with greater accuracy than in-clinic assessment. Twenty-six consecutive PD patients with OH underwent clinical (including home-like assessments of activities of daily living) and kinematic evaluations of balance and gait as well as beat-to-beat blood pressure (BP) monitoring to estimate their association with the risk of falls. Fall frequency was captured by a diary collected prospectively over 6months. When applicable, the sensitivity, specificity, and diagnostic accuracy were measured using the area under the receiver operating characteristics curve (AUC). Additional in-clinic assessments included the OH Symptom Assessment (OHSA), the OH Daily Activity Score (OHDAS), and the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The prevalence of falls was 53.8% over six months. There was no association between the risk of falls and test of gait and postural stability (p ≥ 0.22) or home-like activities of daily living (p > 0.08). Conversely, kinematic data (waist sway during time-up-and-go, jerkiness, and centroidal frequency during postural sway with eyes-opened) predicted the risk of falls with high sensitivity and specificity (> 80%; AUC ≥ 0.81). There was a trend for higher risk of falls in patients with orthostatic mean arterial pressure ≤ 75mmHg. Kinematic but not clinical measures predicted falls in PD patients with OH. Orthostatic mean arterial pressure ≤ 75mmHg may represent a hemodynamic threshold below which falls become more prevalent, supporting the aggressive deployment of corrective measures.

Open-label titration of apomorphine sublingual film in patients with Parkinson's disease and “OFF” episodes

IntroductionThe efficacy and safety of apomorphine sublingual film (APL-130277; APL) for the on-demand treatment of “OFF” episodes associated with Parkinson's disease (PD) was demonstrated in a double-blind trial. Herein we describe the ability of patients to receive effective and tolerable APL dose titration during the open-label titration phase. MethodsAdult patients with levodopa-responsive PD and “OFF” episodes were enrolled. In practically defined “OFF,” patients were observed for a FULL “ON” after their usual morning carbidopa/levodopa (CD/LD) dose and then after titration with APL following each increasing dose (10–35 mg). Antiemetic medication was administered for 3 days before initiation of titration and was continued throughout titration. Motor responses were evaluated predose and postdose using Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III score. Safety outcomes were evaluated. ResultsAmong 141 patients who enrolled in the study and received APL during open-label titration, 109 (77.3%) achieved a FULL “ON” (66.1% at 10–20 mg) and 10 did not. Patients who successfully completed APL dose titration tended to be younger, had a longer mean time since PD diagnosis, and had lower levodopa requirements than those who discontinued during titration for any reason. Change in MDS-UPDRS Part III scores from predose to 30 min postdose after titration with the effective dose of APL (n = 109) was similar across all dose groups. In a post hoc analysis, the magnitude of motor response with APL was ~2-fold higher than with CD/LD 15 min postdose, and the observed peak response occurred earlier with APL than with the trend seen for CD/LD (45 vs 90 min, respectively). Overall, the most common (≥10%) treatment-emergent adverse events (TEAEs) during APL dose titration were nausea (20.6%), yawning (12.1%), dizziness (11.3%), and somnolence (11.3%). Twelve patients discontinued due to TEAEs during APL dose titration, most commonly (≥2%) because of dizziness (2.8%), nausea (2.1%), and somnolence (2.1%). ConclusionAmong eligible patients with PD and “OFF” episodes who had their APL dose successfully titrated to an effective and tolerable level, most were able to do so within the first 3 titrated doses but some required further dose escalations. The use of APL can provide benefit for the treatment of “OFF” episodes.

Parkinson’s Disease, Periodontitis and Patient-Related Outcomes: A Cross-Sectional Study

Background and objectives: People with Parkinson’s disease (PD) may be at risk of having bad periodontal status. A consistent periodontal examination is critical to investigate how it impacts on PD quality of life. We aimed to assess the periodontal status of people with PD, and its association with quality of life and self-perceived xerostomia. Materials and Methods: To this end, from February to March 2020, we consecutively enrolled 28 PD individuals, and motor and non-motor symptoms of PD were assessed using the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS). We performed full-mouth periodontal examination and gathered information on self-perceived quality of life in PD, oral health impact profile (OHIP-14) and xerostomia. Results: The prevalence of periodontitis was 75.0% and most cases were identified as severe (46.4%). Upper extremity rigidity, hand posture and kinetic tremors were significantly correlated with worse periodontal status. PDQ-8 showed to be correlated with self-perceived oral health-related quality of life and xerostomia levels. Conclusions: This group of people with PD had a high prevalence of periodontitis. Deteriorated levels of the upper extremities in advanced stages of PD were associated with worse periodontal status and hygiene habits. Quality of life in PD appears to be associated with self-perceived OHRQoL and xerostomia.