Levodopa-Induced Dyskinesias are Frequent and Impact Quality of Life in Parkinson's Disease: A 5-Year Follow-Up Study.

BACKGROUND: Levodopa-induced dyskinesias (LID) are frequent in Parkinson's disease (PD). OBJECTIVE: To analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients' quality of life (QoL). PATIENTS AND METHODS: PD patients from the 5-year follow-up COPPADIS cohort were included. LID were defined as a non-zero score in the item "Time spent with dyskinesia" of the Unified Parkinson's Disease Rating Scale-part IV (UPDRS-IV). The UPDRS-IV was applied at baseline (V0) and annually for 5 years. The 39-item Parkinson's disease Questionnaire Summary Index (PQ-39SI) was used to asses QoL. RESULTS: The frequency of LID at V0 in 672 PD patients (62.4 ± 8.9 years old; 60.1% males) with a mean disease duration of 5.5 ± 4.3 years was 18.9% (127/672) and increased progressively to 42.6% (185/434) at 5-year follow-up (V5). The frequency of disabling LID, painful LID, and morning dystonia increased from 6.9%, 3.3%, and 10.6% at V0 to 17.3%, 5.5%, and 24% at V5, respectively. Significant independent factors associated with LID (P < 0.05) were a longer disease duration and time under levodopa treatment, a higher dose of levodopa, a lower weight and dose of dopamine agonist, pain severity and the presence of motor fluctuations. LID at V0 (ß = 0.073; P = 0.027; R2 = 0.62) and to develop disabling LID at V5 (ß = 0.088; P = 0.009; R2 = 0.73) were independently associated with a higher score on the PDQ-39SI. CONCLUSION: LID are frequent in PD patients. A higher dose of levodopa and lower weight were factors associated to LID. LID significantly impact QoL.

No evidence for an association of voxel-based morphometry with short-term non-motor outcomes in deep brain stimulation for Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established therapy in advanced Parkinson's disease (PD). Motor and non-motor outcomes, however, show considerable inter-individual variability. Preoperative morphometry-based metrics have recently received increasing attention to explain treatment effects. As evidence for the prediction of non-motor outcomes is limited, we sought to investigate the association between metrics of voxel-based morphometry and short-term non-motor outcomes following STN-DBS in this prospective open-label study. Forty-nine PD patients underwent structural MRI and a comprehensive clinical assessment at preoperative baseline and 6-month follow-up. Voxel-based morphometry was used to assess associations between cerebral volume and non-motor outcomes corrected for multiple comparisons using a permutation-based approach. We replicated existing results associating volume loss of the superior frontal cortex with subpar motor outcomes. Overall non-motor burden, however, was not significantly associated with morphometric features, limiting its use as a marker to inform patient selection and holistic preoperative counselling.

Translation and cross-cultural adaptation of the Spanish version of the King's Parkinson's Disease Pain Scale (KPPS).

PURPOSE: To translate and cross-culturally adapt the King's Parkinson's Disease Pain Scale (KPPS) into Spanish. METHODS: The English KPPS was forward translated into Spanish, back translated, and revised by the original developers. Cross-cultural adaptation of relevant target groups was conducted following COSMIN standards. Cognitive pretesting in Spanish people with Parkinson's Disease (PD) and pain was performed via three semi-structured focus group meetings. Changes were implemented based on qualitative and quantitative analyses. A Delphi study (two rounds) of individual assessments by Spanish experts was conducted. Changes were implemented based on the Content Validity Index (CVI) at item and scale levels (I-CVI/S-CVI). RESULTS: Five Spanish professionals performed the initial translation. Thirty-eight inter-translation inconsistencies were identified, and consensus was reached for a unified version. After back translation and confirmation with scale developers, the pre-final Spanish KPPS was obtained. Cognitive pretesting in 30 people with PD-related pain identified 5 items where terminology changes were made to assure comprehensibility. The Delphi study in 14 Spanish experts underlined the necessity to further modify two items. After the second round, all experts agreed on the modifications and I-CVI and S-CVI were satisfactory. CONCLUSIONS: The KPPS was successfully translated and cross-culturally adapted into Spanish.

The King's Parkinson's Disease Pain Scale (KPPS) was translated into Spanish by 5 independent experts.Cross-cultural validity was assessed by Spanish Parkinson's Disease (PD) patients and neurology experts.The Spanish KPPS adaptation was relevant, understandable, and comprehensive.Rehabilitation professionals will have access to the Spanish KPPS version for assessing PD-related pain in Spanish speaking patients.

Management of Impulse Control and Related Disorders in Parkinson's Disease: An Expert Consensus.

BACKGROUND: Impulse-control and related behavioral disorders (ICBDs) significantly impact the lives of Parkinson's disease (PD) patients and caregivers, with lasting consequences if undiagnosed and untreated. While ICBD pathophysiology and risk factors are well-studied, a standardized severity definition and treatment evidence remain elusive. OBJECTIVE: This work aimed to establish international expert consensus on ICBD treatment strategies. To comprehensively address diverse treatment availabilities, experts from various continents were included. METHODS: From 2021 to 2023, global movement disorders specialists engaged in a Delphi process. A core expert group initiated surveys, involving a larger panel in three iterations, leading to refined severity definitions and treatment pathways. RESULTS: Experts achieved consensus on defining ICBD severity, emphasizing regular PD patient screenings for early detection. General treatment recommendations focused on continuous monitoring, collaboration with significant others, and seeking specialist advice for legal or financial challenges. For mild to severe ICBDs, gradual reduction in dopamine agonists was endorsed, followed by reductions in other PD medications. Second-line treatment strategies included diverse approaches like reversing the last medication change, cognitive behavior therapy, subthalamic nucleus deep brain stimulation, and specific medications like quetiapine, clozapine, and antidepressants. The panel reached consensus on distinct treatment pathways for punding and dopamine dysregulation syndrome, formulating therapy recommendations. Comprehensive discussions addressed management strategies for the exacerbation of either motor or non-motor symptoms following the proposed treatments. CONCLUSION: The consensus offers in-depth insights into ICBD management, presenting clear severity criteria and expert consensus treatment recommendations. The study highlights the critical need for further research to enhance ICBD management. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Economic Burden of Parkinson's Disease: A Multinational, Real-World, Cost-of-Illness Study.

BACKGROUND: Parkinson's disease is now one of the fastest-growing neurodegenerative disorders in the developed world, with an increasing prevalence and associated socioeconomic costs. Progression of the disease leads to a gradual deterioration in patients' quality of life, despite optimal treatment, and both medical and societal needs increase, often with the assistance of paid and/or unpaid caregivers. OBJECTIVE: We aimed to quantify the incremental economic burden of Parkinson's disease by disease severity in a real-world setting across differing geographic regions. METHODS: Demographics, clinical characteristics, health status, patient quality of life, caregiver burden, and healthcare resource utilization data were drawn from the Adelphi Parkinson's Disease Specific Program™, conducted in the USA, five European countries, and Japan. RESULTS: A total of 563 neurologists provided data for 5299 individuals with Parkinson's disease; 61% were male, with a mean age of 64 years. Approximately 15% of individuals were deemed to have advanced disease, with significantly more comorbidities, and a poorer quality of life, than those with non-advanced disease. Overall, the mean annual healthcare resource utilization increased significantly with advancing disease, and resulted in a three-fold difference in the USA and Europe. The main drivers behind the high economic burden included hospitalizations, prescription medications, and indirect costs. CONCLUSIONS: People with Parkinson's disease, and their caregivers, incur a higher economic burden as their disease progresses. Future interventions that can control symptoms or slow disease progression could reduce the burden on people with Parkinson's disease and their caregivers, whilst also substantially impacting societal costs.

Subthalamic stimulation has acute psychotropic effects and improves neuropsychiatric fluctuations in Parkinson's disease.

Background: Subthalamic nucleus deep brain stimulation (STN-DBS) is a well-established treatment for motor complications in Parkinson's disease (PD). However, its effects on neuropsychiatric symptoms remain disputed. The aim of this study was to evaluate the effects of STN-DBS on neuropsychiatric symptoms in PD. Methods: We retrospectively assessed 26 patients with PD who underwent a preoperative levodopa challenge and postoperative levodopa and stimulation challenges 1 year after STN-DBS. Based on the Neuropsychiatric Fluctuations Scale, Neuropsychiatric State Scores and Neuropsychiatric Fluctuation Indices (NFIs) were calculated. Mixed-effects models with random effects for intercept were used to examine the association of Neuropsychiatric State Score and NFI with the different assessment conditions. Results: In acute challenge conditions, there was an estimated increase of 15.9 points in the Neuropsychiatric State Score in stimulation ON conditions (95% CI 11.4 to 20.6, p<0.001) and 7.6 points in medication ON conditions (95% CI 3.3 to 11.9, p<0.001). Neuropsychiatric fluctuations induced by levodopa, quantified with NFI, decreased by 35.54% (95% CI 49.3 to 21.8, p<0.001) 1 year after STN-DBS. Conclusions: Bilateral STN-DBS at therapeutic parameters has acute psychotropic effects similar to levodopa and can modulate and decrease levodopa-induced neuropsychiatric fluctuations.

Neurostimulation for Advanced Parkinson Disease and Quality of Life at 5 Years: A Nonrandomized Controlled Trial.

Importance: Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves quality of life (QOL) in patients with advanced Parkinson disease (PD). However, controlled studies with more than 3 years of follow-up are lacking. Objective: To investigate the long-term effects of STN-DBS on QOL compared with standard-of-care medication (MED). Design, Setting, and Participants: In this prospective, observational, quasi-experimental, longitudinal nonrandomized controlled trial, 183 patients were screened for eligibility and 167 were enrolled from March 1, 2011, to May 31, 2017, at 3 European university centers. Propensity score matching for demographic and clinical characteristics was applied to 108 patients with PD (62 in the STN-DBS group and 46 in the MED group), resulting in a well-balanced, matched subcohort of 25 patients per group. Data analysis was performed from September 2022 to January 2023. Exposure: Treatment for PD of STN-DBS or MED. Main Outcomes and Measures: Assessments included Parkinson's Disease Questionnaire 8 (PDQ-8), Unified PD Rating Scale-motor examination, Scales for Outcomes in PD-activities of daily living (ADL) and motor complications, and levodopa-equivalent daily dose. Within-group longitudinal outcome changes, between-group differences, and correlations of change scores were analyzed. Results: The study population in the analysis included 108 patients (mean [SD] age, 63.7 [8.3] years; 66 [61.1%] male). At 5-year follow-up, PDQ-8 and ADL worsened only in the MED group (PDQ-8 change, -10.9; 95% CI, -19.0 to -2.7; P = .01; ADL change: -2.0; 95% CI, -3.1 to -0.8; P = .002), whereas both outcomes remained stable in the STN-DBS group (PDQ-8 change, -4.3; 95% CI, -13.2 to 4.7; P = .34; ADL change, -0.8; 95% CI, -2.5 to 1.0; P = .38). Changes in PDQ-8 and ADL correlated moderately (rs = .40, P = .008). Furthermore, STN-DBS outcomes were favorable for motor complications (median difference in change scores between STN-DBS and MED, -2.0; 95% CI, -4.0 to -1.0; P = .003), mobility (-1.0; 95% CI, -2.0 to 0; P = .03), and levodopa-equivalent daily dose reduction (-821.4; 95% CI, -1111.9 to -530.8; P < .001). Conclusions and Relevance: This study provides evidence of differences in QOL outcomes at 5-year follow-up between STN-DBS (stable) and MED (worsened), mainly driven by the favorable effect of STN-DBS on mobility (class IIb evidence). The association between changes in QOL and ADL, but not motor impairment or complications, highlights the relative importance of ADL outcomes for long-term DBS assessments. Trial Registration: German ClinicalTrials Registry: DRKS00006735.

Validation of the Kazakh version of the movement disorder Society-Unified Parkinson's disease rating scale.

Background and Purpose: The International Movement Disorder Society revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is widely used in the assessment of the severity of Parkinson's disease (PD). This study aimed to validate the Kazakh version of the MDS-UPDRS, explore its dimensionality, and compare it to the original English version. Methods: The validation was conducted in three phases: first, the English version of the MDS-UPDRS was translated into Kazakh and thereafter back-translated into English by two independent teams; second, the Kazakh version underwent a cognitive pretesting; third, the Kazakh version was tested in 360 native Kazakh-speaking PD patients. Both confirmatory and exploratory factor analyses were performed to validate the scale. We calculated the comparative fit index (CFI) for confirmatory factor analysis and used unweighted least squares for exploratory factor analysis. Results: The CFI was higher than 0.90 for all parts of the scale, thereby meeting the pre-set threshold for the official designation of a validated translation. Exploratory factor analysis also showed that the Kazakh MDS-UPDRS has the analogous factors structure in each part as the English version. Conclusions: The Kazakh MDS-UPDRS had a consistent overall structure as the English MDS-UPDRS, and it was designated as the official Kazakh MDS-UPDRS, which can reliably be used in the Kazakh-speaking populations. Presently, Kazakhstan stands as the sole country in both Central Asia and Transcaucasia with an MDS-approved translated version of the MDS-UPDRS. We expect that other Central Asian and Transcaucasian countries will embark on the MDS Translation Program for MDS-UPDRS in the near future.

Stratifying quality of life outcome in subthalamic stimulation for Parkinson's disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson's disease (PD) improves quality of life (QoL), motor and non-motor symptoms (NMS). However, in previous studies, 43%-49% of patients did not experience clinically relevant postoperative QoL improvement. To inform individualised prediction of postoperative QoL improvement, we developed a stratification analysis of QoL outcomes based on preoperative non-motor total burden, severity of motor progression and motor response in levodopa challenge tests. METHODS: This was a prospective, open-label, multicentre, international study with a 6-month follow-up. A distribution-based threshold identified 'QoL responders' in the PDQuestionnaire-8 Summary Index (PDQ-8 SI). After baseline stratification based on the NMS Scale, Hoehn and Yahr Scale and levodopa response assessed with the Unified PD Rating Scale-III, we compared postoperative QoL response between these strata. To assess the clinical usefulness and statistical feasibility of stratifications, we compared cumulative distribution function curves, respectively PDQ-8 within-stratum variation. RESULTS: All main outcomes improved postoperatively. Based on the 8.1 points threshold for clinically meaningful PDQ-8 SI improvement, only 80/161 patients were classified as 'QoL responders'. The absolute risk reductions for QoL non-response among respective non-motor, motor progression and levodopa response strata were 23%, 8% and 3%, respectively. Only non-motor stratification reduced PDQ-8 within-stratum variation compared with the overall cohort. CONCLUSIONS: Non-motor stratification, but not motor progression or levodopa response stratification, is clinically useful and statistically feasible for personalised preoperative prediction of postoperative QoL outcome of STN-DBS for PD. Our findings highlight that non-motor assessments are necessary components of a case-based, holistic approach of DBS indication evaluations geared towards optimising postoperative QoL outcomes. TRIAL REGISTRATION NUMBER: GermanClinicalTrialsRegister: #6735.

Staging Parkinson's disease according to the MNCD classification correlates with caregiver burden.

BACKGROUND AND OBJECTIVE: Recently, we demonstrated that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (motor, non-motor, cognition, and dependency) and five stages, correlated with disease severity and patients' quality of life. Here, we analyzed the correlation of MNCD staging with PD caregiver's status. PATIENTS AND METHODS: Data from the baseline visit of PD patients and their principal caregiver recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) in this cross-sectional analysis. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), PQ-10, and EUROHIS-QOL 8-item index (EUROHIS-QOL8). RESULTS: Two hundred and twenty-four PD patients (63 ± 9.6 years old; 61.2% males) and their caregivers (58.5 ± 12.1 years old; 67.9% females) were included. The frequency of MNCD stages was 1, 7.6%; 2, 58.9%; 3, 31.3%; and 4-5, 2.2%. A more advanced MNCD stage was associated with a higher score on the ZCBI (p < .0001) and CSI (p < .0001), and a lower score on the PQ-10 (p = .001), but no significant differences were observed in the BDI-II (p = .310) and EUROHIS-QOL8 (p = .133). Moderate correlations were observed between the MNCD total score and the ZCBI (r = .496; p < .0001), CSI (r = .433; p < .0001), and BDI-II (r = .306; p < .0001) in caregivers. CONCLUSION: Staging PD according to the MNCD classification is correlated with caregivers' strain and burden.

Response to levodopa in Parkinson's disease over time. A 4-year follow-up study.

BACKGROUND AND OBJECTIVE: A good response to levodopa is a key factor to indicate device-aided therapies in people with Parkinson's disease (PwPD). The aim of the present study was to analyze the response to levodopa in PwPD with motor fluctuations followed for 4 years. PATIENTS AND METHODS: PwPD with motor fluctuations recruited from January 2016 to November 2017 from the COPPADIS cohort and assessed annually (from baseline to 4-year follow-up) during the OFF and ON states were included in this analysis. At each visit, the Unified Parkinson's Disease Rating Scale - part III (UPDRS-III) was applied during the OFF state (without medication during the last 12 h) and during the ON state. General linear model repeated measures were used to test for changes in the mean UPDRS-III-OFF, UPDRS-III-ON, and ΔUPDRS-III (UPDRS-III-OFF - UPDRS-III-ON) between visits. Levodopa equivalent daily dose (LEDD) was included as covariate. RESULTS: Sixty-three patients (63.94 ± 8.42 years old; 68.3% males) were included. Mean disease duration was 7.81 ± 3.64 years. From baseline to 4-year follow-up visit, a significant increase in both the UPDRS-III-OFF (from 27.98 ± 9.58 to 31.75 ± 12.39; p = 0.003) and the UPDRS-III-ON (from 15.92 ± 7.93 to 18.84 ± 8.17; p = 0.006) was observed despite the significant increase in the LEDD (from 896.35 ± 355.65 to 1085.51 ± 488.29; p = 0.003). However, no significant differences were detected between visits in the ΔUPDRS-III. CONCLUSION: In this cohort of PwPD with motor fluctuations, the response to levodopa did not weaken after a 4-year follow-up.

How can I assess my patients with Parkinson's disease during a busy clinic day?

BACKGROUND: The evaluation of motor impairment in Parkinson's disease (PD) is mainly assessed with the motor subdomain of the Unified Parkinson's Disease Rating scale (UPDRS part III) and, lately, with the MDS-UPDRS part III. To optimize efforts and special needs during specific circumstances in clinical practice, we sought to identify the most sensitive items to assess motor impairment in PD. METHODS: We included the COPPADIS-PD cohort and collected the UPDRS part III at baseline (V0), 12 months (V1), and 24 months (V2). Factor analysis and effect size using Cohen's d formula were performed in the Off and On states at V0, V1, and V2. RESULTS: We included 667 patients with PD, mean age of 62.59 ± 8.91 years, 410 (60.2%) males, with a median HY stage of 2.00 (1.00; 4.00) at baseline. Over time, the most discriminating items were postural stability and body bradykinesia ("arise from chair" and "gait") in the Off state, right and left upper extremity bradykinesia ("finger tap", "hand movements" and "prono/supination") in the On state. Body bradykinesia and right-left finger tapping were the items with the largest effect size (0.93, 0.84, 0.83, respectively) to assess motor improvement after receiving antiparkinsonian medications over time. CONCLUSION: Under specific circumstances, selecting a few items of the UPDRS part III, including postural stability, body bradykinesia, and upper extremity bradykinesia, could be used to create a quick clinical judgment of motor status and improvement in PD.

Cognitive impairment and dementia in young onset Parkinson's disease.

BACKGROUND AND OBJECTIVE: Patients with young-onset Parkinson's disease (YOPD) have a slower progression. Our aim was to analyze the change in cognitive function in YOPD compared to patients with a later onset and controls. PATIENTS AND METHODS: Patients with Parkinson's disease (PD) and controls from the COPPADIS cohort were included. Cognitive function was assessed with the Parkinson's Disease Cognitive Rating Scale (PD-CRS) at baseline (V0), 2-year ± 1 month (V2y), and 4-year ± 3 months follow-up (V4y). Regarding age from symptoms onset, patients were classified as YOPD (< 50 years) or non-YOPD (≥ 50). A score in the PD-CRS < 81 was defined as cognitive impairment (CI): ≤ 64 dementia; 65-80 mild cognitive impairment (MCI). RESULTS: One-hundred and twenty-four YOPD (50.7 ± 7.9 years; 66.1% males), 234 non-YOPD (67.8 ± 7.8 years; 59.3% males) patients, and 205 controls (61 ± 8.3 years; 49.5% males) were included. The score on the PD-CRS and its subscore domains was higher at all visits in YOPD compared to non-YOPD patients and to controls (p < 0.0001 in all analysis), but no differences were detected between YOPD patients and controls. Only non-YOPD patients had significant impairment in their cognitive function from V0 to V4y (p < 0.0001). At V4y, the frequency of dementia and MCI was 5% and 10% in YOPD compared to 25.2% and 22.3% in non-YOPD patients (p < 0.0001). A lower score on the Parkinson's Disease Sleep Scale at baseline was a predictor of CI at V4y in YOPD patients (Adjusted R2 = 0.61; OR = 0.965; p = 0.029). CONCLUSION: Cognitive dysfunction progressed more slowly in YOPD than in non-YOPD patients.

Gender differences in referrals for deep brain stimulation for essential tremor.

Deep brain stimulation (DBS) is an established treatment for essential tremor (ET). Gender differences in DBS have been recognized for Parkinson's disease. In this systematic chart review, we also observed a gender differences in DBS for ET. The main reason was an underrepresentation of women in referrals for surgical evaluation.

Suicidal ideation among people with Parkinson's disease and comparison with a control group.

BACKGROUND: Detection of suicidal ideation (SI) is key for trying to prevent suicide. The aim of this study was to analyze the frequency of SI and related factors in Spanish people with Parkinson's Disease (PwPD) and to compare them with a control group. METHODS: PD patients and controls recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. Two visits were conducted: V0 (baseline); V2 (2-year ± 1 month follow-up). SI was defined as a score ≥1 on item nine of the Beck Depression Inventory-II (BDI-II). Regression analyses were conducted to identify factors related to SI. RESULTS: At baseline, 693 PwPD (60.2% males; 62.59 ± 8.91 years old) and 207 controls (49.8% males; 60.99 ± 8.32 years old) were included. No differences between PwPD and controls were detected in SI frequency at either V0 (5.1% [35/693] vs. 4.3% [9/207]; p = 0.421) or at V2 (5.1% [26/508] vs. 4.8% [6/125]; p = 0.549). Major depression (MD) and a worse quality of life were associated with SI at both visits in PwPD: V0 (MD, OR = 5.63; p = 0.003; PDQ-39, OR = 1.06; p = 0.021); V2 (MD, OR = 4.75; p = 0.027; EUROHIS-QOL8, OR = 0.22; p = 0.006). A greater increase in the BDI-II total score from V0 to V2 was the only factor predicting SI at V2 (OR = 1.21; p = 0.002) along with an increase in the total number of non-antiparkinsonian drugs (OR = 1.39; p = 0.041). CONCLUSION: The frequency of SI (5%) in PwPD was similar to in controls. Depression, a worse quality of life, and a greater comorbidity were related to SI.

Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals.

BACKGROUND: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed. OBJECTIVES: To update LED conversion formulae based on a systematic review. METHODS: The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency. RESULTS: The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon. CONCLUSIONS: The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Prevalence and Factors Associated with Drooling in Parkinson's Disease: Results from a Longitudinal Prospective Cohort and Comparison with a Control Group.

Introduction: Drooling in Parkinson's disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. Patients and Methods. PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30-day follow-up (V2) from 35 centers in Spain from the COPPADIS cohort were included in this longitudinal prospective study. Subjects were classified as with or without drooling according to item 19 of the NMSS (Nonmotor Symptoms Scale) at V0, V1 (1-year ± 15 days), and V2 for patients and at V0 and V2 for controls. Results: The frequency of drooling in PD patients was 40.1% (277/691) at V0 (2.4% (5/201) in controls; p < 0.0001), 43.7% (264/604) at V1, and 48.2% (242/502) at V2 (3.2% (4/124) in controls; p < 0.0001), with a period prevalence of 63.6% (306/481). Being older (OR = 1.032; p = 0.012), being male (OR = 2.333; p < 0.0001), having greater nonmotor symptom (NMS) burden at the baseline (NMSS total score at V0; OR = 1.020; p < 0.0001), and having a greater increase in the NMS burden from V0 to V2 (change in the NMSS total score from V0 to V2; OR = 1.012; p < 0.0001) were identified as independent predictors of drooling after the 2-year follow-up. Similar results were observed in the group of patients with ≤2 years since symptom onset, with a cumulative prevalence of 64.6% and a higher score on the UPDRS-III at V0 (OR = 1.121; p = 0.007) as a predictor of drooling at V2. Conclusion: Drooling is frequent in PD patients even at the initial onset of the disease and is associated with a greater motor severity and NMS burden.

Expanded and Independent Spanish Validation of the MDS-Non Motor Rating Scale.

Background: The Movement Disorder Society-sponsored Non-motor Rating Scale (MDS-NMS) assess the severity and disability caused by non-motor symptoms (NMS) in Parkinson's disease (PD). Objective: This article encapsulates the formal process for completing this program and the data on the first officially approved non-English version of the MDS-NMS (Spanish). Methods: The MDS-NMS translation program involves four steps: translation and back-translation; cognitive pre-testing to ensure that raters and patients understand the scale and are comfortable with its content; field testing of the finalized version; analysis of the factor structure of the tested version against the original English language version for the nine domains that could be analyzed in a confirmatory factor analysis. To be designated an "Official MDS translation," the confirmatory factor analysis Comparative Fit Index had to be ≥0.90. Results: The Spanish MDS-NMS was tested in 364 native-Spanish-speaking patients with PD from seven countries. For all subjects with fully computable data with all domains of the MDS-NMS (n = 349), the Comparative Fit Index was ≥0.90 for the nine eligible domains. Missing data were negligible and moderate floor effect (42.90%) was found for the Non-Motor Fluctuations subscale. Item homogeneity coefficient was adequate, and the correlation of the MDS-NMS domains with other measures for related constructs was acceptable (r s ≥ 0.50). Conclusions: The Spanish version of the MDS-NMS followed the IPMDS Translation Program protocol, reached the criterion to be designated as an Official Translation, and is now available on the MDS website.

Clinical Impression of Severity Index for Parkinson's Disease and Its Association to Health-Related Quality of Life.

Background: Clinical Impression of Severity Index for Parkinson's Disease (CISI-PD) is a simple tool that can easily be used in clinical practice. Few studies have investigated the relationship between health-related quality of life and the CISI-PD. Objective: To analyze the association of CISI-PD scores with those of generic (EQ-5D-5L) and Parkinson's disease (PD) disease-specific (Parkinson's Disease Questionnaire-8 [PDQ-8]) health-related quality of life assessments. Methods: Persons with idiopathic PD in the Swedish Parkinson's Disease registry with simultaneous registrations of CISI-PD and EQ-5D-5L and/or PDQ-8 were included. Correlations with EQ-5D dimensions were analyzed. The relationships between the CISI-PD, EQ-5D-5L, and PDQ-8 were estimated by linear mixed models with random intercept. Results: In the Swedish Parkinson's Disease registry, 3511 registrations, among 2168 persons, fulfilled the inclusion criteria. The dimensions self-care, mobility, and usual activities correlated moderately with the CISI-PD (r s = 0.60, r s = 0.54, r s = 0.57). Weak correlations were found for anxiety/depression and pain/discomfort (r s = 0.39, r s = 0.29) (P values < 0.001). The fitted model included the CISI-PD, age, sex, and time since diagnosis. The CISI-PD had a statistically significant impact on the EQ-5D and PDQ-8 (P values < 0.001). Conclusions: The CISI-PD provides a moderate correlation with the EQ-5D and could possibly be useful as a basis for defining health states in future health economic models and serving as outcomes in managed entry agreements. Nonetheless, the limitation of capturing nonmotor symptoms of the disease remains a shortcoming of clinical instruments, including the CISI-PD.

Non-motor effects of deep brain stimulation in Parkinson's disease motor subtypes.

INTRODUCTION: Deep brain stimulation (DBS) is a well-established treatment for patients with Parkinson's disease (PD) improving quality of life, motor, and non-motor symptoms. However, non-motor effects in PD subtypes are understudied. We hypothesized that patients with 'postural instability and gait difficulty' (PIGD) experience more beneficial non-motor effects than 'tremor-dominant' patients undergoing DBS for PD. METHODS: In this prospective, observational, international multicentre study with a 6-month follow-up, we assessed the Non-Motor Symptom Scale (NMSS) as primary and the following secondary outcomes: Unified PD Rating Scale-motor examination (UPDRS-III), Scales for Outcomes in PD (SCOPA)-activities of daily living (ADL) and -motor complications, PDQuestionnaire-8 (PDQ-8), and levodopa-equivalent daily dose (LEDD). We analysed within-group longitudinal changes with Wilcoxon signed-rank test and Benjamini-Hochberg correction for multiple comparisons. Additionally, we explored outcome between-group differences of motor subtypes with Mann-Whitney U-tests. RESULTS: In 82 PIGD and 33 tremor-dominant patients included in this study, baseline NMSS total scores were worse in PIGD patients, both groups experienced postoperative improvements of the NMSS sleep/fatigue domain, and between-group differences in postoperative outcomes were favourable in the PIGD group for the NMSS total and miscellaneous domain scores. CONCLUSIONS: This study provides evidence of a favourable outcome of total non-motor burden in PIGD compared to tremor-dominant patients undergoing DBS for PD. These differences of clinical efficacy on non-motor aspects should be considered when advising and monitoring patients with PD undergoing DBS.