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Objective: The Progressive Supranuclear Palsy quality of life scale (PSP‐QoL) has been shown to be a useful tool for capturing health‐related quality of life of patients in "everyday life" and in progressive supranuclear palsy (PSP) research. However, at 45 items in length, the questionnaire can take a long time, exhausting PSP patients, in particular if cognitive impaired, which can have a negative impact on the assessment. The aim of this study was to establish a condensed version of the PSP‐QoL for research and routine clinical care. Methods: In this retrospective study, data originating from a German cohort of PSP patients was analyzed. Data from 245 PSP patients were included in this study. The short PSP‐QoL questionnaire was created using a two‐factor solution and item‐total and inter‐item correlations for mental and physical aspects of daily living of the PSP‐QoL followed by confirmatory factor analysis. Results: The final scale included 12 items representing mental (five items) and physical symptoms (seven items). The specified two‐factor model displayed an excellent fit in the confirmatory factor analysis. The short Progressive Supranuclear Palsy Quality of Life scale (PSP‐ShoQoL) correlated moderately with the PSP Rating Scale (r [243] = 0.514, P < 0.001) and Geriatric depression scale (r [231] = 0.548, P < 0.001). Sensitivity to change confirmed a significant decrease in QoL after 12 months. Discussion: In this study, we created a 12‐item PSP‐ShoQoL designed to "facilitate" daily clinical work that correlated strongly with the PSP‐QoL and was sensitive to change. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Head tremor is common in dystonia syndromes and difficult to treat. Deep brain stimulation (DBS) is a therapeutic option in medically‐refractory cases. In most DBS‐centers, the globus pallidus internus (GPi) is targeted in patients with predominant dystonia and the ventrointermediate nucleus of the thalamus (Vim) in predominant tremor. The aim of the study was to evaluate the effect of GPi‐ versus Vim‐DBS in dystonic or essential head tremor. Methods: All patients with dystonia or essential tremor (ET) (n = 381) who underwent DBS surgery at our institution between 1999 and 2020 were screened for head tremor in our database according to predefined selection criteria. Of the 33 patients meeting inclusion criteria tremor and dystonia severity were assessed at baseline, short‐ (mean 10 months) and long‐term follow‐up (41 months) by two blinded video‐raters. Results: Twenty‐two patients with dystonic head tremor received either GPi‐ (n = 12) or Vim‐stimulation (n = 10), according to the prevailing clinical phenotype. These two groups were compared with 11 patients with ET, treated with Vim‐stimulation. The reduction in head tremor from baseline to short‐ and long‐term follow‐up was 60–70% and did not differ significantly between the three groups. Conclusions: GPi‐DBS effectively and sustainably reduced head tremor in idiopathic dystonia. The effect was comparable to the effect of Vim‐DBS on head tremor in dystonia patients with predominant limb tremor and to the effect of Vim‐DBS on head tremor in ET. [ABSTRACT FROM AUTHOR]

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: Thalamic deep brain stimulation (DBS) is established for medically refractory tremor syndromes and globus pallidus stimulation (GPi‐DBS) for medically refractory dystonia syndromes. For combined tremor and dystonia syndromes, the best target is unclear. Objectives: We present four patients with two different profiles whose clinical course demonstrates that our current analysis of clinical symptomatology is not a sufficient predictor of surgical success. Methods: Outcome parameters were assessed with observer‐blinded video ratings and included the Fahn‐Tolosa‐Marin‐Tremor Rating Scale (FTM‐TRS) and the Unified Dystonia Rating Scale (UDRS). Results: Two patients with "predominant lateralized action tremor" of the hands and mild cervical dystonia showed no relevant tremor improvement after GPi‐DBS, but UDRS improved (mean, 45%). Rescue ventral intermediate nucleus of the thalamus (Vim)‐DBS electrodes were implanted and both patients benefited significantly with a mean tremor reduction of 51%. Two other patients with "axial‐predominant action tremor of the trunk and head" associated with cervical dystonia underwent bilateral Vim‐DBS implantation with little effect on tremor (24% reduction in mean FTM‐TRS total score) and no effect on dystonic symptoms. GPi rescue DBS was implanted and showed a significant effect on tremor (63% reduction in mean FTM‐TRS) and dystonia (49% reduction in UDRS). Conclusions: The diagnosis of dystonic tremor alone is not a sufficient predictor to establish the differential indication of GPi‐ or Vim‐DBS. Further criteria (eg, proximal‐distal distribution of tremor/dystonia) are needed to avoid rescue surgery in the future. On the other hand, the course of our patients encourages rescue surgery in such severely disabled patients if the first target fails. [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]

Dystonia is a debilitating disease with few treatment options. One effective option is deep brain stimulation (DBS) to the internal pallidum. While cervical and generalized forms of isolated dystonia have been targeted with a common approach to the posterior third of the nucleus, large-scale investigations regarding optimal stimulation sites and potential network effects have not been carried out. Here, we retrospectively studied clinical results following DBS for cervical and generalized dystonia in a multicenter cohort of 80 patients. We model DBS electrode placement based on pre- and postoperative imaging and introduce an approach to map optimal stimulation sites to anatomical space. Second, we investigate which tracts account for optimal clinical improvements, when modulated. Third, we investigate distributed stimulation effects on a whole-brain functional connectome level. Our results show marked differences of optimal stimulation sites that map to the somatotopic structure of the internal pallidum. While modulation of the striatopallidofugal axis of the basal ganglia accounted for optimal treatment of cervical dystonia, modulation of pallidothalamic bundles did so in generalized dystonia. Finally, we show a common multisynaptic network substrate for both phenotypes in the form of connectivity to the cerebellum and somatomotor cortex. Our results suggest a brief divergence of optimal stimulation networks for cervical vs. generalized dystonia within the pallidothalamic loop that merge again on a thalamo-cortical level and share a common whole-brain network. [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: Infections are feared complications following deep brain stimulation in 1.9 to 17.6% of cases. These infections can necessitate the removal of implants, which carries the risk of life-threatening withdrawal syndromes, especially in patients suffering from Parkinson's disease. In this report, we describe our procedure of removing an infected implanted pulse generator (IPG) and cables with contralateral replacement in the same session. Methods: We retrospectively analysed all patients with transpositions of an IPG and cables between 2017 and 2020 in a single-centre, university hospital setting. Medical records of all patients undergoing this particular surgical procedure were systematically reviewed. The shortest follow-up time was 12 months. Results: Between 2017 and 2020, we had 6 patients with a high risk of withdrawal syndrome in whom an infected IPG with cables was removed and replaced on the opposite side in the same session. There were postoperative complications in 2 patients: in one, the generator had to be re-affixed, and in the second, a skin transplant was required over one electrode because of skin necrosis. No case of invasive infection was seen, and the stimulation therapy was not interrupted. Conclusion: One-session removal of an IPG and cables with contralateral replacement seems to be an effective therapy for patients at high risk of withdrawal syndrome. [ABSTRACT FROM AUTHOR]

Introduction: The rate of intracranial hemorrhage (ICH) after deep brain stimulation (DBS) is between 1.5 and 6.1%, with prolonged deficits occurring in 0.4–2.5% of the patients. This retrospective study investigates whether the prophylactic administration of tranexamic acid (TA) to patients with abnormal platelet function detected preoperatively by platelet function analyzer (PFA) lowered the risk for an ICH event. Methods: We performed a systematic review of the medical records of 485 consecutively admitted patients who underwent bilateral DBS surgery in a single-center university hospital setting between 2009 and 2018. The cohort was split into two groups. In one group, preoperative PFA screening was performed (n = 156, patients recruited from 2014 to 2018), and TA was administered if platelet function was abnormal. No preoperative PFA was performed in the second group (n = 359, patients recruited from 2009 to 2013). Both cohorts were analyzed for the occurrence of ICH, defined by (i) detection of ICH in routine postoperative magnetic resonance/computed tomography imaging or (ii) in non-routine imaging for the onset of new neurological symptoms. Results: Fourteen of the 156 screened patients (9%) showed reproducible PFA-100 closure abnormalities (3 with von Willebrand disease, 11 with no identifiable cause of platelet dysfunction). Two of the 156 patients (1.3%) in this cohort revealed an ICH on imaging, 1 of whom (0.6%) exhibited a prolonged neurological deficit as a result of ICH. In the cohort without platelet testing, 11 of the 329 patients (3.3%) demonstrated ICH on imaging, of whom 5 (1.5%) suffered from a prolonged neurological deficit. Conclusion: In this retrospective study, the screening and the administration of TA appeared to lower the risk of an ICH by 1.8%. One patient with von Willebrand disease suffered an ICH despite TA treatment. A prospective study is needed to clarify the impact of platelet testing and TA administration on the of incidence ICH. [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]

Deep brain stimulation of the internal globus pallidus is a highly effective and established therapy for primary generalized and cervical dystonia, but therapeutic success is compromised by a non-responder rate of up to 25%, even in carefully-selected groups. Variability in electrode placement and inappropriate stimulation settings may account for a large proportion of this outcome variability. Here, we present probabilistic mapping data on a large cohort of patients collected from several European centres to resolve the optimal stimulation volume within the pallidal region. A total of 105 dystonia patients with pallidal deep brain stimulation were enrolled and 87 datasets (43 with cervical dystonia and 44 with generalized dystonia) were included into the subsequent 'normative brain' analysis. The average improvement of dystonia motor score was 50.5 ± 30.9% in cervical and 58.2 ± 48.8% in generalized dystonia, while 19.5% of patients did not respond to treatment (<25% benefit). We defined probabilistic maps of anti-dystonic effects by aggregating individual electrode locations and volumes of tissue activated (VTA) in normative atlas space and ranking voxel-wise for outcome distribution. We found a significant relation between motor outcome and the stimulation volume, but not the electrode location per se. The highest probability of stimulation induced motor benefit was found in a small volume covering the ventroposterior globus pallidus internus and adjacent subpallidal white matter. We then used the aggregated VTA-based outcome maps to rate patient individual VTAs and trained a linear regression model to predict individual outcomes. The prediction model showed robustness between the predicted and observed clinical improvement, with an r2 of 0.294 (P < 0.0001). The predictions deviated on average by 16.9 ± 11.6 % from observed dystonia improvements. For example, if a patient improved by 65%, the model would predict an improvement between 49% and 81%. Results were validated in an independent cohort of 10 dystonia patients, where prediction and observed benefit had a correlation of r2 = 0.52 (P = 0.02) and a mean prediction error of 10.3% (±8.9). These results emphasize the potential of probabilistic outcome brain mapping in refining the optimal therapeutic volume for pallidal neurostimulation and advancing computer-assisted planning and programming of deep brain stimulation. [ABSTRACT FROM AUTHOR]

Background: Reduced muscle strength is an independent risk factor for falls and related to postural instability in individuals with Parkinson’s disease. The ability of resistance training to improve postural control still remains unclear. Objective: To compare resistance training with balance training to improve postural control in people with Parkinson’s disease. Methods: 40 patients with idiopathic Parkinson’s disease (Hoehn&Yahr: 2.5–3.0) were randomly assigned into resistance or balance training (2x/week for 7 weeks). Assessments were performed at baseline, 8- and 12-weeks follow-up: primary outcome: Fullerton Advanced Balance (FAB) scale; secondary outcomes: center of mass analysis during surface perturbations, Timed-up-and-go-test, Unified Parkinson’s Disease Rating Scale, Clinical Global Impression, gait analysis, maximal isometric leg strength, PDQ-39, Beck Depression Inventory. Clinical tests were videotaped and analysed by a second rater, blind to group allocation and assessment time. Results: 32 participants (resistance training: n = 17, balance training: n = 15; 8 drop-outs) were analyzed at 8-weeks follow-up. No significant difference was found in the FAB scale when comparing the effects of the two training types (p = 0.14; effect size (Cohen’s d) = -0.59). Participants from the resistance training group, but not from the balance training group significantly improved on the FAB scale (resistance training: +2.4 points, Cohen’s d = -0.46; balance training: +0.3 points, Cohen’s d = -0.08). Within the resistance training group, improvements of the FAB scale were significantly correlated with improvements of rate of force development and stride time variability. No significant differences were found in the secondary outcome measures when comparing the training effects of both training types. Conclusions: The difference between resistance and balance training to improve postural control in people with Parkinson’s disease was small and not significant with this sample size. There was weak evidence that freely coordinated resistance training might be more effective than balance training. Our results indicate a relationship between the enhancement of rate of force development and the improvement of postural control. Trial Registration: ClinicalTrials.gov ID: [ABSTRACT FROM AUTHOR]