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Background: The decision to choose invasive treatments for Parkinson's disease (PD) is complex and needs careful consideration. Objectives: Although the recommendations of the European Academy of Neurology/Movement Disorder Society European Section guideline for invasive therapies of PD are useful, the different clinical profiles of people with PD who seek advice for possible invasive therapy need further attention. Methods and Results: Here we describe 8 clinical standard situations of people with PD unsatisfied with their current oral treatment where invasive therapies may be considered. These are PD patients presenting with the following symptoms: (1) severe motor fluctuations, (2) beginning of levodopa‐responsive fluctuations, severe tremor at (3) young or (4) advanced age, (5) impulse control disorders and related behavioral disorders, (6) hallucinations and psychosis, (7) minimal cognitive impairment or mild dementia, and (8) patients in need of palliative care. For some of these conditions, evidence at lower level or simple clinical considerations exist. Conclusions: There are no one‐fits‐all answers, but physician and patient should discuss each option carefully considering symptom profile, psychosocial context, availability of therapy alternatives, and many other factors. The current paper outlines our proposed approach to these circumstances. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Deep brain stimulation of the subthalamic nucleus (STN‐DBS) is an effective and evidence‐based treatment for idiopathic Parkinson's disease (iPD). A minority of patients does not sufficiently benefit from STN‐DBS. Objective: The predictive validity of the levodopa challenge for individual patients is analyzed. Methods: Data from patients assessed with a preoperative Levodopa‐test and a follow‐up examination (mean ± standard deviation: 9.15 months ±3.39) from Kiel (n = 253), Berlin (n = 78) and Toronto (n = 98) were studied. Insufficient DBS outcome was defined as an overall UPDRS‐III reduction <33% compared to UPDRS‐III in med‐off at baseline or alternatively if the minimal clinically important improvement of 5 points was not reached. Single UPDRS‐items and sub‐scores were dichotomized. Following exploratory analysis, we trained supervised regression‐ and classification models for outcome prediction. Results: Data analysis confirmed significant correlation between the absolute UPDRS‐III reduction during Levodopa challenge and after stimulation. But individual improvement was inaccurately predicted with a large range of up to 30 UPDRS III points. Further analysis identified preoperative UPDRS‐III/med‐off‐scores and preoperative Levodopa‐improvement as most influential factors. The models for UPDRS‐III and sub‐scores improvement achieved comparably low accuracy. Conclusions: With large prediction intervals, the Levodopa challenge use for patient counseling is limited, though remains important for excluding non‐responders to Levodopa. Despite these deficiencies, the current practice of patient selection is highly successful and builds not only on the Levodopa challenge. However, more specific motor tasks and further paraclinical tools for prediction need to be developed. [ABSTRACT FROM AUTHOR]

Background: The EARLYSTIM trial demonstrated for Parkinson's disease patients with early motor complications that deep brain stimulation of the subthalamic nucleus (STN‐DBS) and best medical treatment (BMT) was superior to BMT alone. Objective: This prospective, ancillary study on EARLYSTIM compared changes in blinded speech intelligibility assessment between STN‐DBS and BMT over 2 years, and secondary outcomes included non‐speech oral movements (maximum phonation time [MPT], oral diadochokinesis), physician‐ and patient‐reported assessments. Methods: STN‐DBS (n = 102) and BMT (n = 99) groups underwent assessments on/off medication at baseline and 24 months (in four conditions: on/off medication, ON/OFF stimulation—for STN‐DBS). Words and sentences were randomly presented to blinded listeners, and speech intelligibility rate was measured. Statistical analyses compared changes between the STN‐DBS and BMT groups from baseline to 24 months. Results: Over the 2‐year period, changes in speech intelligibility and MPT, as well as patient‐reported outcomes, were not different between groups, either off or on medication or OFF or ON stimulation, but most outcomes showed a nonsignificant trend toward worsening in both groups. Change in oral diadochokinesis was significantly different between STN‐DBS and BMT groups, on medication and OFF STN‐DBS, with patients in the STN‐DBS group performing slightly worse than patients under BMT only. A signal for clinical worsening with STN‐DBS was found for the individual speech item of the Unified Parkinson's Disease Rating Scale, Part III. Conclusion: At this early stage of the patients' disease, STN‐DBS did not result in a consistent deterioration in blinded speech intelligibility assessment and patient‐reported communication, as observed in studies of advanced Parkinson's Disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Orthostatic hypotension (OH) in Parkinson's disease (PD) is frequent and associated with impairments in quality of life and reduced activities of daily living. Abdominal binders (AB) and compression stockings (CS) have been shown to be effective non-pharmacological treatment options. Objective: Here, we investigate the effect of AB versus CS on physical activity using a digital mobility outcome (sit to stand [STS] frequency) collected in the usual environment as a primary endpoint. Methods: We enrolled 16 PD patients with at least moderate symptomatic OH. In a randomized, single-blinded, controlled, crossover design, participants were assessed without OH treatment over 1 week (baseline), then were given AB or CS for 1 week and subsequently switched to the other treatment arm. The primary outcome was the number of real-life STS movements per hour as assessed with a lower back sensor. Secondary outcomes included real-life STS duration, mean/systolic/diastolic blood pressure drop (BPD), orthostatic hypotension questionnaire (OHQ), PD quality of life (PDQ-39), autonomic symptoms (SCOPA-AUT), non-motor symptoms (NMSS), MDS-UPDRS, and activities of daily living (ADL/iADL). Results: Real-life STS frequency on CS was 4.4±4.1 per hour compared with 3.6±2.2 on AB and 3.6±1.8 without treatment (p = 1.0). Concerning the secondary outcomes, NMSS showed significant improvement with CS and AB. OHQ and SCOPA-AUT improved significantly with AB but not CS, and mean BPD drop worsened with CS but not AB. Mean STS duration, PDQ-39, MDS-UPDRS, ADL, and iADL did not significantly change. Conclusion: Both AB and CS therapies do not lead to a significant change of physical activity in PD patients with at least moderate symptomatic OH. Secondary results speak for an effect of both therapies concerning non-motor symptoms, with superiority of AB therapy over CS therapy. [ABSTRACT FROM AUTHOR]

Background: Subthalamic nucleus deep brain stimulation (STN‐DBS) effectively treats motor symptoms and quality of life (QoL) of advanced and fluctuating early Parkinson's disease. Little is known about the relation between electrode position and changes in symptom control and ultimately QoL. Objectives: The relation between the stimulated part of the STN and clinical outcomes, including the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS) and the quality‐of‐life questionnaire, was assessed in a subcohort of the EARLYSTIM study. Methods: Sixty‐nine patients from the EARLYSTIM cohort who underwent DBS, with a comprehensive clinical characterization before and 24 months after surgery, were included. Intercorrelations of clinical outcome changes, correlation between the affected functional parts of the STN, and changes in clinical outcomes were investigated. We further calculated sweet spots for different clinical parameters. Results: Improvements in the UPDRS III and Parkinson's Disease Questionnaire (PDQ‐39) correlated positively with the extent of the overlap with the sensorimotor STN. The sweet spots for the UPDRS III (x = 11.6, y = −13.1, z = −6.3) and the PDQ‐39 differed (x = 14.8, y = −12.4, z = −4.3) ~3.8 mm. Conclusions: The main influence of DBS on QoL is likely mediated through the sensory‐motor basal ganglia loop. The PDQ sweet spot is located in a posteroventral spatial location in the STN territory. For aspects of QoL, however, there was also evidence of improvement through stimulation of the other STN subnuclei. More research is necessary to customize the DBS target to individual symptoms of each patient. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Objective: The response of freezing of gait (FOG) to deep brain stimulation of the subthalamic nucleus (STN-DBS) is controversial and depends on many poorly controlled factors. On the other hand, a clinical predictor for the individual patient is needed to counsel the patient regarding this symptom.Methods: A cohort of 124 patients undergoing STN-DBS was evaluated based on the video-documented Levodopa test at baseline in the OFF- and ON-drug condition and postoperatively in the best condition (ON-drug/ON-stim) and the worst condition (OFF-drug/ON-stim). We compared the freezing item of the Unified Parkinson's disease rating scale (#14), the UPDRS III total score, and FOG severity rated during four provoking situations with regard to its predictive value.Results: We found 'FOG during the turning task' to be the best predictor with an ROC-value of 0.857 compared to 0.603 for the UPDRS Item 14 and 0.583 for the total UPDRS III. An improvement of 1 or 2 grades of the turning item during the preoperative levodopa test predicts an improvement during the worst condition postoperatively of 1 grade or more with an 80% probability.Conclusion: This FOG prediction test is simple and clinically useful. The test needs to be studied in a prospective study. [ABSTRACT FROM AUTHOR]

Background: Freezing of gait (FOG) in Parkinson's disease (PD) is provoked by specific situations. The sensitivity of these situations to detect FOG and the relative FOG response to l-dopa and subthalamic nucleus deep brain stimulation (STN-DBS) is unknown.Methods: Two blinded reviewers analyzed the video recordings of a standardized patient assessment before and 10 months after DBS-implantation of 124 PD patients with positive FOG according to the Unified Parkinson Rating Scale part II item 14. Baseline evaluations were done under 2 conditions (OFF- and ON-drug states). Postoperatively, the patients were evaluated under 4 conditions (OFF-drug/OFF-stim, OFF-drug/ON-stim, ON-drug/OFF-stim, and ON-drug/ON-stim). FOG frequency and its severity was rated during different provoking situations (start, turning, reaching a destination and open space hesitations) during a standardized walking task. Cumulative link mixed models were calculated to investigate the immediate and carry-over effect of medication and stimulation.Results: Eighty-one percent of patients presented FOG at least in one provoking situation on video assessment. During turning, the FOG severity was significantly worse than for the other subtypes (p < 0.0001). Both interventions improve all FOG subtypes similarly. The effect size of l-dopa and STN-DBS on subtypes were similar (p > 0.05), but the combined intervention had a stronger effect on FOG severity (p < 0.0001) compared to each intervention separately. FOG severity was lower at follow-up OFF compared to baseline OFF condition (p < 0.02) demonstrating a carry-over effect of STN-DBS.Conclusion: Turning is the most sensitive provoking situation for gait freezing. STN-DBS and l-dopa improve all FOG subtypes similarly, their effect is stronger in combination. [ABSTRACT FROM AUTHOR]

Background: Effects of DBS on freezing of gait and other axial signs in PD patients are unclear.Objective: Secondary analysis to assess whether DBS affects these symptoms within a large randomized controlled trial comparing DBS of the STN combined with best medical treatment and best medical treatment alone in patients with early motor complications (EARLYSTIM-trial).Methods: One hundred twenty-four patients were randomized in the stimulation group and 127 patients in the best medical treatment group. Presence of freezing of gait was assessed in the worst condition based on item-14 of the UPDRS-II at baseline and follow-up. The posture, instability, and gait-difficulty subscore of the UPDRS-III, and a gait test including quantification of freezing of gait and number of steps, were performed in both medication-off and medication-on conditions.Results: Fifty-two percent in both groups had freezing of gait at baseline based on UPDRS-II. This proportion decreased in the stimulation group to 34%, but did not change in the best medical treatment group at 24 months (P = 0.018). The steps needed to complete the gait test decreased in the stimulation group and was superior to the best medical treatment group (P = 0.016). The axial signs improved in the stimulation group compared to the best medical treatment group (P < 0.01) in both medication-off and medication-on conditions.Conclusions: Within the first 2 years of DBS, freezing of gait and other axial signs improved in the medication-off condition compared to best medical treatment in these patients. © 2019 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Objective: Two strategies are known for turning while walking: step turns (the direction change is performed with 3 steps or more) and spin turns (turning on one/both feet simultaneously). It is unknown which strategy patients with Parkinson's disease (PD) choose and if l-dopa and STN-DBS are influencing this strategy.Methods: Video-recordings of 171 PD patients that completed 180° turns were analyzed by two blinded raters before surgery, both off and on l-dopa, and one year after STN-DBS-implantation. The strategies were classified: 1) spin 2) step and 3) mixed (spin plus step) strategy. The characteristics of the patients with different strategies were compared.Results: Interrater reliability for classification of turning strategy showed high agreement (κ = 0.894). The distribution of the preferred strategy differed significantly between treatment conditions (untreated, treated with l-dopa, l-dopa plus stimulation; X2(4) = 67.2, p < 0.0001). The spin turn was found in 10.5% of patients OFF-drug, 23.5% ON-drug and in 38.8% ON-drug/ON-stim condition. In the three treatment conditions patients with spin turns had significantly lower UPDRS III scores compared to people with step turns (p = 0.017, p = 0.001, p = 0.006, respectively); step turn patients had poorer postural instability and gait disorders (PIGD) scores (p = 0.04, p = 0.002, p = 0.04, respectively).Conclusion: The turn strategy can be reliably identified in clinical settings and is a simple motor sign. The spin turn is associated with better motor performance. Since improvements in motor score in patients with fluctuations are also related to behavioral changes, we cannot exclude that the turn strategy also represents a feature of psycho-motor interaction. [ABSTRACT FROM AUTHOR]

Purpose: The decision for subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease (PD) relies on clinical predictors. Whether genetic variables could predict favourable or unfavourable decisions is under investigation.Objective: First, we aimed to reproduce the previous observation that SNCA rs356220 was associated with favourable STN-DBS motor response. In additional exploratory analyses, we studied if other PD risk and progression variants from the latest GWAS are associated with therapeutic outcome. Further, we evaluated the predictive value of polygenic risk scores.Methods: We comprehensively genotyped patients from the EarlyStim cohort using NeuroChip, and assessed the clinico-genetic associations with longitudinal outcome parameters.Results: The SNCA rs356220 variant did not predict UPDRS III outcomes. However, it was associated with quality of life improvement in secondary analyses. Several polymorphisms from previously identified GWAS hits predicted motor or quality of life outcomes in DBS patients. Polygenic risk scores did not predict any outcome parameter.Conclusions: Our findings support the hypothesis that different common genetic markers are associated with favourable quality of life outcomes of STN-DBS in PD. These findings can be the basis for further validation in larger and independent cohorts. [ABSTRACT FROM AUTHOR]