Turkish Standardization of Movement Disorders Society Unified Parkinson's Disease Rating Scale and Unified Dyskinesia Rating Scale.

Formulas were developed to define tremor dominant (TD) and postural instability/gait difficulty (PIGD) phenotypes of Parkinson's Disease (PD) using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). TD and PIGD designations, based on the original Unified Parkinson's Disease Rating Scale (UPDRS), provided useful designations for classifying different phenotypes of PD. With the advent of the MDS-UPDRS, a valid set of calculations for these phenotypes is needed. UPDRS and MDS-UPDRS scores were collected on 877 PD patients. TD/PIGD scores were calculated using the UPDRS formula for all patients. Comparable TD and PIGD items from the MDS-UPDRS were used to calculate new ratios. Data were analyzed using receiver operating characteristic models. The new MDS-UPDRS TD/PIGD ratios accounted for a significant area under the curve compared with the UPDRS classification. Optimal sensitivity and specificity were obtained with MDS-UPDRS cutoff scores of ≥1.15 for TD classification and ≤0.90 for PIGD. The development of comparable and valid PIGD and TD scores from the MDS-UPDRS provides a clear method for clinicians and researchers to transition from the original UPDRS to the new MDS-UPDRS in categorizing patients with different clinical phenotypes. © 2013 Movement Disorder Society.

Regulatory recommendations favor outcomes combining objective and patient input. The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the most commonly used scale in Parkinson's disease (PD), includes patient and investigator ratings in distinct parts, but original clinimetric analyses failed to confirm the validity of combining parts by simple summing. The aim was to develop clinimetrically valid constructs for combining patient-reported Part 2 and investigator-rated Part 3 MDS-UPDRS scores. Using 7888 MDS-UPDRS scores, we assessed construct validity of combined Part 2 and Part 3 items using exploratory factor analysis (EFA) and graded item response theory (IRT) with threshold criteria: comparative fit index≥0.9 (EFA) and discrimination parameters≥0.65 (IRT). The direct sum of Parts 2+3 failed to meet the threshold for a valid outcome of PD severity (comparative fit index, CFI=0.855). However, a two-domain construct combining item scores for tremor and non-tremor domains from Parts 2 and 3 confirmed validity, meeting both EFA and IRT criteria as distinct but correlated indices of disease severity (CFI=0.923; discrimination mean 2.197 ± 0.480 [tremor] and 1.737 ± 0.344 [non-tremor] domains). The sum of Parts 2+3 is not clinimetrically sound. However, considering tremor and non-tremor items of both Parts 2 and 3 as two outcomes results in a valid summary of PD motor severity that leverages simultaneous patient- and investigator-derived measures. This analytic application addresses regulatory prioritizations and retains the well-validated MDS-UPDRS items. In future interventional trials, we suggest that tremor and non-tremor components of PD motor severity from Parts 2+3 be monitored and analyzed to accurately detect objective changes that integrate the patient's voice. © 2023 International Parkinson and Movement Disorder Society.

This systematic review and meta-analysis investigated the long-term efficacy of Amantadine for Levodopa-induced dyskinesia (LID) in Parkinson's disease patients. Our analysis focused on longer-term motor outcomes, including those which are under-reported in the literature. We identified relevant articles by searching four online databases and reviewing citations. The primary outcomes included the Unified Parkinson's Disease Rating Scale (UPDRS) or Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV and daily "ON" time; secondary outcomes included UPDRS/MDS-UPDRS III and IVa, Unified Dyskinesia Rating Scale (UDysRS) total score, and daily "OFF" time. For each outcome, we conducted meta-analyses for numerous time-points after beginning treatment: "up to 13weeks", "up to 16weeks", "12 to 16weeks", and "38 to 101weeks". Our outcome measure was the Standardized Mean Differences (SMDs) between the pooled Amantadine-Levodopa and Levodopa only (control) groups. We found associations between Amantadine and each motor outcome. The most considerable was an SMD of -0.73 points for Amantadine compared to control for the UPDRS/MDS-UPDRS IV at up to 16weeks after beginning treatment (P<0.0001). However, the magnitude of most associations decreased with time, indicating declining long-term efficacy. We also identified a risk of added "adverseness"; 11 studies had patient-reported adverse events, mainly overlaid with known symptoms. Our findings suggest that Amantadine is an effective adjunct medication for improving LID and broader Parkinson's disease symptoms. However, evidence of its declining long-term efficacy and "adverseness" have important implications for its use in Parkinson's disease therapy.

Cognitive pretesting, a qualitative step in scale development, precedes field testing and assesses the difficulty of instrument completion for examiners and respondents. Cognitive pretesting assesses respondent interest, attention span, discomfort, and comprehension, and highlights problems with the logical structure of questions/response options that can affect understanding. In the past this approach was not consistently used in the development or revision of movement disorders scales. We applied qualitative cognitive pretesting using testing guides in development of the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The guides were based on qualitative techniques, verbal probing and "think-aloud" interviewing, to identify problems with the scale from the patient and rater perspectives. English-speaking Parkinson's disease patients and movement disorders specialists (raters) from multiple specialty clinics in the United States, Western Europe and Canada used the MDS-UPDRS and completed the testing guides. Two rounds of cognitive pretesting were necessary before proceeding to field testing of the revised scale to assess clinimetric properties. Scale revisions based on cognitive pretesting included changes in phrasing, simplification of some questions, and addition of a reassuring statement explaining that not all PD patients experience the symptoms described in the questions. The strategy of incorporating cognitive pretesting into scale development and revision provides a model for other movement disorders scales. Cognitive pretesting is being used in translating the MDS-UPDRS into multiple languages to improve comprehension and acceptance and in the development of a new Unified Dyskinesia Rating Scale for Parkinson's disease patients.

ABSTRACTBackgroundLevodopa‐carbidopa intestinal gel infusion (LCIG) is an effective therapy for advanced Parkinson's disease (PD). Opicapone (OPC) is an enzyme inhibitor that enhances the bioavailability of levodopa in the brain.ObjectivesThis study evaluates the effect of Opicapone addition in PD‐LCIG patients, assessing its impact on motor fluctuations and dyskinesias. Secondly, the study analyses the impact of OPC on non‐motor symptoms, LCIG dosage, and peripheral neuropathy.MethodsIn this pilot study, 22 PD patients on LCIG were randomized to receive OPC or not, based on persistent or reemergent fluctuations. The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), Unified Dyskinesia Rating Scale (UDysRS), Montreal Cognitive Assessment (MoCA), electroneurography (ENG), LCIG doses, homocysteine, vitamin B12, and folic acid levels were measured at baseline (T0) and after 12 months (T1).ResultsEleven patients added OPC (addOPC group), while 11 maintained standard treatment (nOPC group). At baseline, both groups had similar disease duration and severity. At T1, the addOPC group showed significant: (i) improvement in motor fluctuations evaluated by the MDS‐UPDRS part IV; (ii) reduction in dyskinesias (UDyRS); (iii) decrease in LCIG infusion rate; (iv) improvement in motor and non‐motor symptoms (MDS‐UPDRS parts I‐III); (v) increase in Vitamin B12. No significant differences were observed in the ENG data, and no serious adverse events occurred. Four addOPC patients (36%) discontinued OPC after 15 ± 2 months, mainly due to hallucinations.ConclusionsOPC addition appeared well tolerated and beneficial in reducing motor fluctuations, dyskinesia, and LCIG dose. Randomized controlled trials are needed to confirm these findings.

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.

ADS‐5102 is a long‐acting, extended‐release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy, and tolerability of ADS‐5102 in Parkinson's disease (PD) patients with levodopa‐induced dyskinesia. This was a randomized, double‐blind, placebo‐controlled, parallel‐group study of 83 PD patients with troublesome dyskinesia assigned to placebo or one of three doses of ADS‐5102 (260 mg, 340 mg, 420 mg) administered daily at bedtime for 8 weeks. The primary efficacy analysis compared change from baseline to week 8 in Unified Dyskinesia Rating Scale (UDysRS) total score for 340 mg ADS‐5102 versus placebo. Secondary outcome measures included change in UDysRS for 260 mg, 420 mg, Fatigue Severity Scale (FSS), Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS), patient diary, Clinician's Global Impression of Change, and Parkinson's Disease Questionnaire (PDQ‐39). ADS‐5102 340 mg significantly reduced dyskinesia versus placebo (27% reduction in UDysRS, P = 0.005). In addition, ADS‐5102 significantly increased ON time without troublesome dyskinesia, as assessed by PD patient diaries, at 260 mg (P = 0.004), 340 mg (P = 0.008) and 420 mg (P = 0.018). Adverse events (AEs) were reported for 82%, 80%, 95%, and 90% of patients in the placebo, 260‐mg, 340‐mg, and 420‐mg groups, respectively. Constipation, hallucinations, dizziness, and dry mouth were the most frequent AEs. Study withdrawal rates were 9%, 15%, 14%, and 40% for the placebo, 260‐mg, 340‐mg, and 420‐mg groups, respectively. All study withdrawals in the active treatment groups were attributable to AEs. ADS‐5102 was generally well tolerated and resulted in significant and dose‐dependent improvements in dyskinesia in PD patients. © 2015 Adamas Pharmaceuticals, Inc. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

BackgroundThe 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.ObjectiveTo 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.MethodsPivotal 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.ResultsThe 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.ConclusionAnchored 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.

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.

The Unified Wilson's Disease Rating Scale (UWDRS) was first introduced in 2007 to assess neurologic status and impairment in patients with Wilson's disease (WD). However, major issues have been raised, including the lack of assessment of mental and psychiatric status, the lack of instructions for the assessment of certain motor functions, difficulties with gait and posture assessment, and heterogenous response options for questions across the scale. The development of a modified version of the UWDRS (mUWDRS) was proposed. A new version of UWDRS with revised wording and options was created, incorporating items from the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the Unified Dyskinesia Rating Scale, and the Pantothenate Kinase Associated Neurodegeneration Disease Rating Scale (PKAN-DRS). As in the original, part I of the mUWDRS assesses the level of consciousness. Part II is now divided into two partly self-reported subscales: part IIa assesses 10 daily living activities and a new part IIb addresses cognitive functioning, mental and behavioral status. Part III assesses neurologic status as before, but with modifications for gait and posture items. After 2 rounds of cognitive pretesting, mUWDRS was validated in 7 patients by 8 neurologists for interrater agreement (Fleiss kappa or Kuder Richardson Coefficient) and for internal consistency (Cronbach's alpha). In the pilot test, interrater agreement with mUWDRS was almost perfect or substantial, with index values of 1 for part I, 0.90 for part IIa, 0.93 for cognitive functioning and 0.86 for behavioral status in part IIb, and 0.826 for part III. A high level of internal consistency was observed, with Cronbach's α of 0.82 for part II and 0.84 for part III. The mUWDRS, designed to assess both motor and nonmotor symptoms of WD and functional impairment, performed well in pilot testing. Since the modified version of the WD rating scale has a good interrater agreement, a proper validity study is planned to be conducted. The scale is available on: https://www.movementdisorders.org/MDS/MDS-Clinical-Outcome-Assessment.htm.

BackgroundEvaluating the discrepancies between patient‐reported measures and clinician examination has implications for formulating individual treatment regimens.ObjectiveThis study investigated the association between health outcomes and level of self‐reported motor‐related function impairment relative to clinician‐examined motor signs.MethodsRecently diagnosed PD patients were evaluated using the Parkinson's Progression Marker Initiative (PPMI, N = 420) and the PASADENA phase II clinical trial (N = 316). We calculated the average normalized difference between each participant's part II and III MDS‐UPDRS (Movement Disorder Society Unified Parkinson's Disease Rating Scale) scores. Individuals with score differences <25th or >75th percentiles were labeled as low‐ and high‐self‐reporters, respectively (those between ranges were labeled intermediate‐self‐reporters). We compared a wide range of clinical/biomarker readouts among these three groups, using Kruskal–Wallis nonparametric and Pearson's χ2 tests. Spearman's correlations were tested for associations between MDS‐UPDRS subscales.ResultsIn both cohorts, high‐self‐reporters reported the largest impairment/symptom experience for most motor and nonmotor patient‐reported variables. By contrast, these high‐self‐reporters were similar to or less impaired on clinician‐examined and biomarker measures. Patient‐reported nonmotor symptoms on MDS‐UPDRS part IB showed the strongest positive correlation with self‐reported motor‐related impairment (PPMI rs = 0.54, PASADENA rs = 0.52). This correlation was numerically stronger than the part II and clinician‐examined MDS‐UPDRS part III correlation (PPMI rs = 0.38, PASADENA rs = 0.28).ConclusionSelf‐reported motor‐related impairments reflect not only motor signs/symptoms but also other self‐reported nonmotor measures. This may indicate (1) a direct impact of nonmotor symptoms on motor‐related functioning and/or (2) the existence of general response tendencies in how patients self‐rate symptoms. Our findings suggest further investigation into the suitability of MDS‐UPDRS II to assess motor‐related impairments. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Validation of the Hebrew version of the Movement Disorder Society—Unified Parkinson's Disease Rating Scale

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

Background/Objective: Numerous studies have examined motor and cognitive decline in neurodegenerative diseases such as Parkinson’s Disease (PD) and results vary considerably. Studies also show that decline does not occur synchronously across all aspects of cognition or motor functions in PD. The goal was to examine if correlations exist between decline in specific motor and cognitive functions. Experimental Design: A cohort of 15 PD patients (age 49-81;6 female) and 9 healthy controls (age 53-75;4 female) were enrolled and their motor and cognitive functions were assessed. Decline in motor function, covering tremor, rigidity and bradykinesia was evaluated using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MS-UPDRS) scores. Cognition, covering attention, memory, language, and visuospatial functions, was assessed using the Montreal Cognitive Assessment (MoCA) test. Inertial measurement units (recording at 100 Hz), placed on both wrists, recorded linear acceleration and angular velocity while subjects performed the pronation/supination and kinetic tremor tasks of the MS-UPDRS. Using angular velocity, response time (RT) to initiate movement in each task was computed. Data analysis correlated MS-UPDRS scores with MoCA scores, and RTs. Results: There were no significant correlations between MS-UPDRS and cognitive MoCA scores. There was a significant relationship between deficits in visuospatial function (MoCA) and increased RT in the pronation/supination task. Conclusion/Potential Impact: Using correlation analyses, no correlation was found between MS-UPDRS and MoCA scores. However, RT on the pronation/supination task correlated positively with visuospatial deficits, suggesting a common voluntary attentional deficit. Although no relationship was found between a clinical score of bradykinesia and RT, measures of movement velocities (measured but not analyzed) may correlate better. Identification of interrelating factors between hard-to-measure cognitive and easy-to-measure motor changes in PD patients may aid clinicians in implementing simple and timely interventions to more easily track and ameliorate cognitive deficits and improve patients' overall functional status.

Objectives: The study aimed to investigate the association of anticholinergic burden with polypharmacy, the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), and the modified Hoehn and Yahr (HY) staging system in Parkinson's disease (PD). Patients and methods: The cross-sectional study included 75 patients (38 males, 37 females; mean age: 65.7±9.6 years; range, 32 to 86 years) who were admitted between January 2023 and January 2024. Demographic characteristics, systemic diseases, medications, MDS-UPDRS, and modified HY were recorded. Polypharmacy was defined as the use of five or more medications at the same time. The anticholinergic burden was calculated using the Anticholinergic Cognitive Burden (ACB) scale. Patients were divided into two groups: those with an ACB risk score ≥3 (high risk) and those with a risk score &lt;3 (low risk). Results: When analyzed according to ACB scale risk status, 41 patients with PD were found to be at high risk for anticholinergic burden (score ≥3). The presence of at least one comorbid disease was more common in the high-risk group than in the low-risk group (p&lt;0.05). The presence of unipolar depression was higher in the high-risk group (p=0.001). Frequency of polypharmacy was higher in the high-risk group (73.2% vs. 32.4%; p=0.001). In regression analysis, a high ACB score was statistically associated with modified HY Stage 4 when confounding factors were excluded (odds ratio=12.80; p=0.030). Conclusion: Patients with polypharmacy in PD had higher ACB scores (&gt;3) and depression as a comorbidity in these patients. A high ACB risk score was associated with modified HY Stage 4 when adjusted for confounding factors. The anticholinergic risk might be highest in the advanced stage of PD. Therefore, patients diagnosed with PD should be questioned about their drug history and evaluated for anticholinergic drug use at every visit.