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Linda Veith Sanches,1,* Stephan Greten,1,* Johanna Doll-Lee,1 Sophia Marie Rogozinski,1 Johanne Heine,1 Lea Krey,1 Sarana Ulaganathan,1 Ida Jensen,1,2 Matthias Höllerhage,1 Sam Sadeghi Sani,1 Günter U Höglinger,1– 4 Florian Wegner,1 Martin Klietz1 1Department of Neurology, Hannover Medical School, Hannover, Germany; 2Department of Neurology, Ludwig-Maximilians-Universität (LMU) Munich, Munich, Germany; 3Munich Cluster for Systems Neurology, SyNergy, Munich, Germany; 4German Center for Neurodegenerative Diseases, DZNE, Munich, Germany*These authors contributed equally to this workCorrespondence: Stephan Greten, Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, Hannover, 30625, Germany, Tel +49 511 532-6462, Fax +49 511 532-6677, Email Greten.stephan@mh-hannover.deIntroduction: Neuropsychiatric symptoms in particular impair health-related quality of life (QoL) of patients with Parkinson’s disease and atypical Parkinsonian syndromes. For this reason, various scales have been developed for detection of neuropsychiatric symptoms, such as the Scale for evaluation of neuropsychiatric disorders in Parkinson’s disease (SEND-PD).Objective: First, the objective of this study was to explore the interrelation between the SEND-PD and clinical parameters in patients with Parkinson’s disease and thus confirm its validity. In addition, the applicability in a well-defined cohort of patients with atypical Parkinsonian syndromes was investigated for the very first time.Methods: A clinically well-defined cohort of 122 patients with Parkinson’s disease (PD), 55 patients with Progressive Supranuclear Palsy (PSP) and 33 patients with Multiple System Atrophy (MSA) were analyzed. First, the SEND-PD was correlated with established disease-specific scores in patients with PD. Next, the results of the SEND-PD were compared between the different Parkinsonian syndromes.Results: The SEND-PD showed a strong significant correlation with several scores, especially the UPDRS I (Rho = 0.655) and GDS-15 (Rho = 0.645). Depressive burden was significantly higher in MSA patients in comparison to the PD patient cohort (PD, 3.8 ± 3.3; MSA, 5.45 ± 3.87), while PSP patients showed significantly less psychotic (PD 1.6 ± 2.1; PSP 0.6 ± 0.9) and impulse control disorders (PD 0.3 ± 1.0; PSP 0.02 ± 0.1).Conclusion: The SEND-PD is a useful, brief and highly applicable screening tool for neuropsychiatric symptoms in PD, but not in atypical Parkinsonism, as their unique neuropsychiatric symptom composition is not fully captured.Keywords: neuropsychiatric symptoms, SEND-PD, Parkinsonian syndromes

Background: Multiple system atrophy (MSA), an atypical parkinsonian syndrome, is a rapidly progressive neurodegenerative disease with currently no established fluid biomarkers available. MSA is characterized by an oligodendroglial α-synucleinopathy, progressive neuronal cell loss and concomitant astrocytosis. Here, we investigate glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) as fluid biomarkers for differential diagnosis, assessment of clinical disease severity and prediction of disease progression in MSA., Methods: GFAP and NfL levels were analyzed in plasma and CSF samples of 47 MSA patients as well as 24 Parkinson's disease (PD) and 25 healthy controls (HC) as reference cohorts. In MSA, biomarker levels were correlated to baseline and longitudinal clinical disease severity (UMSARS scores)., Results: In MSA, GFAP levels in CSF and plasma predicted baseline clinical disease severity as indicated by UMSARS scores, while NfL levels predicted clinical disease progression as indicated by longitudinal changes in UMSARS scores. Cross-sectionally, NfL levels in CSF and plasma were significantly elevated in MSA compared to both PD and HC. Receiver operating curves (ROC) indicated high diagnostic accuracy of NfL for distinguishing MSA from PD (CSF: AUC = 0.97, 95% CI 0.90-1.00; plasma: AUC = 0.90, 95% CI 0.81-1.00)., Discussion: In MSA, GFAP shows promise as novel biomarker for assessing current clinical disease severity, while NfL might serve as biomarker for prediction of disease progression and differential diagnosis of MSA against PD., (© 2024. The Author(s).)

Background : Anticholinergic adverse effects pose a relevant threat to patients, in particular elderly and cognitively impaired patients. Patients with Parkinsonian syndromes are especially at risk from anticholinergic adverse effects due to the often-required complex drug therapy. Aims : The aim of this study was to evaluate the potential effect of the anticholinergic burden on motor and non-motor symptoms in Parkinson's disease and atypical Parkinsonian syndromes. Methods: This cross-sectional, monocentric retrospective data analysis included 151 patients with Parkinson's disease (PD), 63 with progressive supranuclear palsy (PSP), and 36 with multiple system atrophy (MSA). The anticholinergic burden of patients' medications was determined using two established scores: the Anticholinergic Drug Scale (ADS) and the German Anticholinergic Burden Scale (GABS). These scores were compared between the different diseases and correlated with several disease-specific scores. Results : Anticholinergic burden was higher in patients with PD, in particular, compared to PSP. In the PD group, anticholinergic burden showed a weak correlation with almost all analyzed clinical scores and the number of administered drugs. The UMSARS I and II showed a significant correlation with the anticholinergic burden in MSA patients. In general, the GABS-measured anticholinergic burden was significantly higher compared to the ADS-measured. Conclusions : The calculated anticholinergic burden affected motor and non-motor symptoms in patients with various Parkinsonian syndromes poorly. Since the GABS also contains basic anti-parkinsonian drugs, this score tended to overestimate the anticholinergic burden in patients with Parkinsonian syndromes and, therefore, seemed less appropriate for this application.

Background: Diagnostic criteria for progressive supranuclear palsy (PSP) include midbrain atrophy in MRI and hypometabolism in [ 18 F]fluorodeoxyglucose (FDG)-positron emission tomography (PET) as supportive features. Due to limited data regarding their relative and sequential value, there is no recommendation for an algorithm to combine both modalities to increase diagnostic accuracy. This study evaluated the added value of sequential imaging using state-of-the-art methods to analyse the images regarding PSP features., Methods: The retrospective study included 41 PSP patients, 21 with Richardson's syndrome (PSP-RS), 20 with variant PSP phenotypes (vPSP) and 46 sex- and age-matched healthy controls. A pretrained support vector machine (SVM) for the classification of atrophy profiles from automatic MRI volumetry was used to analyse T1w-MRI (output: MRI-SVM-PSP score). Covariance pattern analysis was applied to compute the expression of a predefined PSP-related pattern in FDG-PET (output: PET-PSPRP expression score)., Results: The area under the receiver operating characteristic curve for the detection of PSP did not differ between MRI-SVM-PSP and PET-PSPRP expression score (p≥0.63): about 0.90, 0.95 and 0.85 for detection of all PSP, PSP-RS and vPSP. The MRI-SVM-PSP score achieved about 13% higher specificity and about 15% lower sensitivity than the PET-PSPRP expression score. Decision tree models selected the MRI-SVM-PSP score for the first branching and the PET-PSPRP expression score for a second split of the subgroup with normal MRI-SVM-PSP score, both in the whole sample and when restricted to PSP-RS or vPSP., Conclusions: FDG-PET provides added value for PSP-suspected patients with normal/inconclusive T1w-MRI, regardless of PSP phenotype and the methods to analyse the images for PSP-typical features., Competing Interests: Competing interests: H-JH has used atlas-based volumetric MRI analysis in industry-sponsored research projects. CB received a grant from the Hilde-Ulrichs-Stiftung, served as a consultant for Bial, Hormosan Pharma, Merz Pharmaceuticals and Zambon and received honoraria for scientific presentations from Abbvie, Bial, Stada Pharma, TAD Pharma, UCB Pharma and Zambon. MP-N received lecture fees from Abbott, Abbvie, Boston Scientific and served as consultant for Medtronic, Boston Scientific, Abbott, Zambon and Abbvie. SK was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy–ID 390857198), the Ehrmann Foundation and the Lüneburg Heritage. SK receives research funding from CurePSP and reports travel support from Life Molecular Imaging outside the submitted work. MK received honoraria for scientific presentations from Abbvie and Ever Pharma. JL reports speaker fees from Bayer Vital, Biogen, EISAI, TEVA and Roche, consulting fees from Axon Neuroscience and Biogen, author fees from Thieme medical publishers and W. Kohlhammer medical publishers and is inventor in a patent 'Oral Phenylbutyrate for Treatment of Human 4-Repeat Tauopathies' (EP 23 156 122.6) filed by LMU Munich. In addition, he reports compensation for serving as chief medical officer for MODAG, is beneficiary of the phantom share program of MODAG and is inventor in a patent 'Pharmaceutical Composition and Methods of Use' (EP 22 159 408.8) filed by MODAG, all activities outside the submitted work. J-JR received speaker honoraria from GE Healthcare. OS received research support from Life Molecular Imaging. HB received reader honoraria from Life Molecular Imaging and speaker honoraria from Novartis/AAA. MPW received speaker or consultancy honoraria from Alexion, Bayer Healthcare, Biogen, Biologix, Bristol Myers Squibb, Celgene, Genilac, Imcyse, IXICO, Icometrix, Medison, Merck-Serono, Novartis, Roche, Sanofi-Genzyme. Publication royalties from Springer and Elsevier. GH was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy–ID 390857198) and within the Hannover Cluster RESIST (EXC 2155–project number 39087428), the EU/EFPIA/Innovative Medicines Initiative (2) Joint Undertaking (IMPRIND grant no 116060), the European Joint Programme on Rare Diseases (Improve-PSP), Deutsche Forschungsgemeinschaft (DFG, HO2402/6-2 Heisenberg Program, HO2402/18-1 MSAomics), the VolkswagenStiftung (Niedersächsisches Vorab), the Petermax-Müller Foundation (Etiology and Therapy of Synucleinopathies and Tauopathies); participated in indurtry-sponsored research projects from Abbvie, Biogen, Biohaven, Novartis, Roche, Sanofi, UCB; served as a consultant for Abbvie, Alzprotect, Aprineua, Asceneuron, Bial, Biogen, Biohaven, Kyowa Kirin, Lundbeck, Novartis, Retrotope, Roche, Sanofi, UCB; received honoraria for scientific presentations from Abbvie, Bayer Vital, Bial, Biogen, Bristol Myers Squibb, Kyowa Kirin, Roche, Teva, UCB, Zambon; received publication royalties from Academic Press, Kohlhammer and Thieme. All other authors declare that they have no potential conflicts of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Several magnetic resonance imaging (MRI) measures have been suggested as progression biomarkers in progressive supranuclear palsy (PSP), and some PSP staging systems have been recently proposed., Objective: Comparing structural MRI measures and staging systems in tracking atrophy progression in PSP and estimating the sample size to use them as endpoints in clinical trials., Methods: Progressive supranuclear palsy-Richardson's syndrome (PSP-RS) patients with one-year-follow-up longitudinal brain MRI were selected from the placebo arms of international trials (NCT03068468, NCT01110720, NCT01049399) and the DescribePSP cohort. The discovery cohort included patients from the NCT03068468 trial; the validation cohort included patients from other sources. Multisite age-matched healthy controls (HC) were included for comparison. Several MRI measures were compared: automated atlas-based volumetry (44 regions), automated planimetric measures of brainstem regions, and four previously described staging systems, applied to volumetric data., Results: Of 508 participants, 226 PSP patients including discovery (n = 121) and validation (n = 105) cohorts, and 251 HC were included. In PSP patients, the annualized percentage change of brainstem and midbrain volume, and a combined index including midbrain, frontal lobe, and third ventricle volume change, were the progression biomarkers with the highest effect size in both cohorts (discovery: >1.6; validation cohort: >1.3). These measures required the lowest sample sizes (n < 100) to detect 30% atrophy progression, compared with other volumetric/planimetric measures and staging systems., Conclusions: This evidence may inform the selection of imaging endpoints to assess the treatment efficacy in reducing brain atrophy rate in PSP clinical trials, with automated atlas-based volumetry requiring smaller sample size than staging systems and planimetry to observe significant treatment effects. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

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., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: As the most rapidly increasing neurodegenerative disease worldwide, Parkinson's disease is highly relevant to society. Successful treatment requires active patient participation. Patient education has been successfully implemented for many chronic diseases, such as diabetes and could also provide people with Parkinson's disease with skills to manage the disease better and to participate in shared decision making., Material and Methods: To prepare the implementation of a concept for patient education for people with Parkinson's disease, a structured consensus study was conducted and a pilot project formatively evaluated. The structured consensus study included experts from all over Germany. It consisted of two online surveys and an online consensus conference. The formative evaluation was conducted as three focus groups. Transcripts were evaluated using content-structuring qualitative content analysis., Results: From the consensus procedure 59 consented statements emerged, mainly regarding the contents of a patient school and a group size of 6-8 persons. Only two statements could not be consented. The formative evaluation detected a tendency towards a positive attitude for a digital training format and a very positive evaluation of the contents., Discussion: Overall, important recommendations for a patient school can be drawn from this study. The following subjects require further investigation: format, inclusion criteria, group composition and inclusion of caregivers., (© 2024. The Author(s).)

Background: Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patients' safety and management., Objectives: To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients., Methods: Cross-sectional data of MSA patients according to Gilman et al. (2008) diagnostic criteria and control patients without neurodegenerative diseases (non-ND) were collected from German, multicenter cohorts. The prevalence of comorbidities according to WHO ICD-10 classification and drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were identified using AiDKlinik®., Results: The analysis included 254 MSA and 363 age- and sex-matched non-ND control patients. MSA patients exhibited a significantly higher burden of comorbidities, in particular diseases of the genitourinary system. Also, more medications were prescribed MSA patients, resulting in a higher prevalence of polypharmacy. Importantly, the risk of potential drug-drug interactions, including severe interactions and contraindicated combinations, was elevated in MSA patients. When comparing MSA-P and MSA-C subtypes, MSA-P patients suffered more frequently from diseases of the genitourinary system and diseases of the musculoskeletal system and connective tissue., Conclusions: MSA patients face a substantial burden of comorbidities, notably in the genitourinary system. This, coupled with increased polypharmacy and potential drug interactions, highlights the complexity of managing MSA patients. Clinicians should carefully consider these factors when devising treatment strategies for MSA patients., (© 2024. The Author(s).)

Background: Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients., Objectives: To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease., Methods: Cross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik®., Results: In total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions., Conclusions: PSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients., (© 2023. The Author(s).)

Background: To date, studies on positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) in progressive supranuclear palsy (PSP) usually included PSP cohorts overrepresenting patients with Richardson's syndrome (PSP-RS)., Objectives: To evaluate FDG-PET in a patient sample representing the broad phenotypic PSP spectrum typically encountered in routine clinical practice., Methods: This retrospective, multicenter study included 41 PSP patients, 21 (51%) with RS and 20 (49%) with non-RS variants of PSP (vPSP), and 46 age-matched healthy controls. Two state-of-the art methods for the interpretation of FDG-PET were compared: visual analysis supported by voxel-based statistical testing (five readers) and automatic covariance pattern analysis using a predefined PSP-related pattern., Results: Sensitivity and specificity of the majority visual read for the detection of PSP in the whole cohort were 74% and 72%, respectively. The percentage of false-negative cases was 10% in the PSP-RS subsample and 43% in the vPSP subsample. Automatic covariance pattern analysis provided sensitivity and specificity of 93% and 83% in the whole cohort. The percentage of false-negative cases was 0% in the PSP-RS subsample and 15% in the vPSP subsample., Conclusions: Visual interpretation of FDG-PET supported by voxel-based testing provides good accuracy for the detection of PSP-RS, but only fair sensitivity for vPSP. Automatic covariance pattern analysis outperforms visual interpretation in the detection of PSP-RS, provides clinically useful sensitivity for vPSP, and reduces the rate of false-positive findings. Thus, pattern expression analysis is clinically useful to complement visual reading and voxel-based testing of FDG-PET in suspected PSP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Brain magnetic resonance imaging (MRI) is used to support the diagnosis of progressive supranuclear palsy (PSP). However, the value of visual descriptive, manual planimetric, automatic volumetric MRI markers and fully automatic categorization is unclear, particularly regarding PSP predominance types other than Richardson's syndrome (RS)., Objectives: To compare different visual reading strategies and automatic classification of T1-weighted MRI for detection of PSP in a typical clinical cohort including PSP-RS and (non-RS) variant PSP (vPSP) patients., Methods: Forty-one patients (21 RS, 20 vPSP) and 46 healthy controls were included. Three readers using three strategies performed MRI analysis: exclusively visual reading using descriptive signs (hummingbird, morning-glory, Mickey-Mouse), visual reading supported by manual planimetry measures, and visual reading supported by automatic volumetry. Fully automatic classification was performed using a pre-trained support vector machine (SVM) on the results of atlas-based volumetry., Results: All tested methods achieved higher specificity than sensitivity. Limited sensitivity was driven to large extent by false negative vPSP cases. Support by automatic volumetry resulted in the highest accuracy (75.1% ± 3.5%) among the visual strategies, but performed not better than the midbrain area (75.9%), the best single planimetric measure. Automatic classification by SVM clearly outperformed all other methods (accuracy, 87.4%), representing the only method to provide clinically useful sensitivity also in vPSP (70.0%)., Conclusions: Fully automatic classification of volumetric MRI measures using machine learning methods outperforms visual MRI analysis without and with planimetry or volumetry support, particularly regarding diagnosis of vPSP, suggesting the use in settings with a broad phenotypic PSP spectrum. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Lipedema is a widespread disease with painful accumulations of subcutaneous fat in the legs and arms. Often, obesity co-occurs. Many patients suffer from impairment in mobility and mental health. Obesity and mental health in turn can be positively influenced by physical activity. In this study, we aimed to examine the interrelations between pain and physical activity on mental health in lipedema patients. In total, 511 female lipedema patients (age M = 40.16 ± 12.45 years, BMI M = 33.86 ± 7.80 kg/m 2 ) filled in questionnaires measuring pain, physical activity, and mental health (PHQ-9; WHOQOL-BREF with subscales mental, physical, social, environmental, and overall health). Response surface analyses were calculated via R statistics. The explained variance was high for the model predicting depression severity (R 2 = 0.18, p < 0.001) and physical health (R 2 = 0.30, p < 0.001). Additive incongruence effects of pain and physical activity on depression severity, mental, physical, and overall health were found (all p < 0.001). In our study, physical activity and pain synergistically influenced physical, mental, and overall health. The pain not only led to low mental health but also interfered with the valuable potential of engaging in physical activity in lipedema patients.

Background: Progressive supranuclear palsy (PSP) is an atypical Parkinsonian syndrome characterized by supranuclear gaze palsy, early postural instability, and a frontal dysexecutive syndrome. Contrary to normal brain magnetic resonance imaging in Parkinson's disease (PD), PSP shows specific cerebral atrophy patterns and alterations, but these findings are not present in every patient, and it is still unclear if these signs are also detectable in early disease stages., Objective: The aim of the present study was to analyze the metabolic profile of patients with clinically diagnosed PSP in comparison with matched healthy volunteers and PD patients using whole-brain magnetic resonance spectroscopic imaging (wbMRSI)., Methods: Thirty-nine healthy controls (HCs), 29 PD, and 22 PSP patients underwent wbMRSI. PSP and PD patients were matched for age and handedness with HCs. Clinical characterization was performed using the Movement Disorder Society Unified Parkinson's Disease Rating Scale, PSP rating scale, and DemTect (test for cognitive assessment)., Results: In PSP patients a significant reduction in N-acetyl-aspartate (NAA) was detected in all brain lobes. Fractional volume of the cerebrospinal fluid significantly increased in PSP patients compared to PD and healthy volunteers., Conclusions: In PSP much more neuronal degeneration and cerebral atrophy have been detected compared with PD. The most relevant alteration is the decrease in NAA in all lobes of the brain, which also showed a partial correlation with clinical symptoms. However, more studies are needed to confirm the additional value of wbMRSI in clinical practice. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Lipedema, as a disabling and consequential disease, is gaining more awareness due to its potential omnipresence. Patients suffering from lipedema show a characteristic painful display of symmetric accumulations of adipose tissue. The combination of swelling, pain and decreased quality of life (QOL) is outstanding for the diagnosis. The aim of this study was to identify the effect of liposuction in terms of the QOL for patients and underline important factors of current and pending research regarding surgical therapy of lipoedema., Methods: Patients suffering from lipedema prior to and after receiving liposuction at our hospital were included in this study. Patients completed a lipedema-specific self-designed 50 item questionnaire: the World Health Organization Quality of Life BREF (WHOQOL-BREF) and the Patient Health Questionnaire 9 (PHQ-9). A linear mixed model was used for outcome analysis., Results: In total, 511 patients completed a questionnaire prior to the surgery at primary presentation to the hospital and a total number of 56 patients completed a questionnaire after liposuction. A total of 34 of these patients filled in both questionnaires prior to and after surgery. The general characteristics of the disease, such as daily symptoms and psychological health, pertinently improved after surgery., Conclusions: Liposuction can have a general improving effect on the QOL of patients, both in private and professional life. Liposuction may currently be the most evident and promising method in the treatment of lipedema.

Purpose: To determine the nature and frequency of duplicate prescriptions (DPs) in the emergency department (ED) by utilization of a novel categorization of DPs which differentiates between appropriate DPs (ADPs) and potentially inappropriate DPs (PIDPs)., Methods: In this retrospective cohort study, adult patients who presented to the ED for internal medicine of a large university hospital in northern Germany in 2018 and 2019 were screened for the presence of DPs. Descriptive statistical methods were used to characterize the nature and frequency of PIDPs compared to the frequency of ADPs., Results: A total of 4208 patients were enrolled into the study. The median age of the study population was 63 years (interquartile range (IQR) 48-77), 53.9% were female. The patients took a median of 5 drugs (IQR 3-9). 10.9% of the study population were affected by at least one PIDP (at least one grade-1 PIDP: 6.1%; at least one grade-2 PIDP: 4.5%; at least one grade-3 PIDP: 1.1%). Non-opioid analgesics accounted for the majority of grade-1 PIDPs, while inhalatives were most frequently responsible for grade-2 and grade-3 PIDPs. Nearly half of the study population (48.6%) displayed at least one ADP., Conclusion: PIDPs pose a frequent pharmacological challenge in the ED. The medication review should comprise a systematic screening for PIDPs with a particular focus on non-opioid analgesics and inhalatives. ADPs were detected more frequently than PIDPs, questioning the predominant notion in the medical literature that DPs are exclusively deleterious., (© 2022. The Author(s).)

Neuropsychological assessment needs a more profound grounding in psychometric theory. Specifically, psychometrically reliable and valid tools are required, both in patient care and in scientific research. The present study examined convergent and discriminant validity of some of the most popular indicators of executive functioning (EF). A sample of 96 neurological inpatients (aged 18-68 years) completed a battery of standardized cognitive tests (Raven's matrices, vocabulary test, Wisconsin Card Sorting Test, verbal fluency test, figural fluency test). Convergent validity of indicators of intelligence (Raven's matrices, vocabulary test) and of indicators of EF (Wisconsin Card Sorting Test, verbal fluency test, figural fluency) were calculated. Discriminant validity of indicators of EF against indicators of intelligence was also calculated. Convergent validity of indicators of intelligence (Raven's matrices, vocabulary test) was good ( r xtyt = 0.727; R 2 = 0.53). Convergent validity of fluency indicators of EF against executive cognition as indicated by performance on the Wisconsin Card Sorting Test was poor (0.087 ≤ r xtyt ≤ 0.304; 0.008 ≤ R 2 ≤ 0.092). Discriminant validity of indicators of EF against indicators of intelligence was good (0.106 ≤ r xtyt ≤ 0.548; 0.011 ≤ R 2 ≤ 0.300). Our conclusions from these data are clear-cut: apparently dissimilar indicators of intelligence converge on general intellectual ability. Apparently dissimilar indicators of EF (mental fluency, executive cognition) do not converge on general executive ability. Executive abilities, although non-unitary, can be reasonably well distinguished from intellectual ability. The present data contribute to the hitherto meager evidence base regarding the validity of popular indicators of EF.

Adverse drug reactions (ADRs) constitute a frequent cause of hospitalization in older people. The risk of ADRs is increased by the prescription of potentially inappropriate medications for older people (PIMs). The PRISCUS list and the FORTA classification represent established tools to detect PIMs. The aim of the present study was to examine the prevalence and characteristics of PIM prescriptions on the gerontopsychiatric ward of a university hospital in Germany. To this aim, medication charts of 92 patients (mean age 75.9 ± 7.7 years; 66.3% female) were analyzed on a weekly basis until patient discharge by utilization of the PRISCUS list and the FORTA classification. Overall, 335 medication reviews comprising 2363 drug prescriptions were analyzed. 3.0% of the prescribed drugs were PIMs according to the PRISCUS list, with benzodiazepines and Z-drugs accounting for nearly half (49.3%) of all PIM prescriptions. 30.4% of the patients were prescribed at least one PRISCUS-PIM, while 43.5% of the study population took at least one FORTA class D drug. A considerable proportion of gerontopsychiatric patients were affected by PIMs; however, the overall number of PIM prescriptions in the study population was low. Further improvements in the quality of prescribing should target the use of sedating agents such as benzodiazepines and Z-drugs. Physicians should be aware of discrepancies between the PRISCUS list and the FORTA classification., (© 2022. The Author(s).)

Objectives: Information on medication-related problems (MRPs) in elderly psychiatric patients is scarce. In the present study, we analyzed the frequency and characteristics of MRPs in patients ≥60 years treated on the gerontopsychiatric ward of Hannover Medical School in 2019., Methods: Taking advantage of an interdisciplinary approach, two independent investigators screened hospital discharge letters of 230 psychiatric inpatients for clinically relevant MRPs, followed by validation through an interdisciplinary expert panel. Drug interactions as a subset of MRPs were analyzed with the aid of two different drug interaction programs., Results: 230 patients (63.0% female, mean age 73.7 ± 8.4 years, median length of stay 18 days) were prescribed a median of 6 drugs. In total, 2180 MRPs were detected in the study population and 94.3% of the patients exhibited at least one MRP. Patients displayed a median of 7 MRPs (interquartile range 3-15). Pharmacodynamic interactions accounted for almost half of all MRPs (48.1%; 1048/2180). The number of drugs prescribed and the number of MRPs per patient showed a strong linear relationship (adjusted R 2  = 0.747)., Conclusion: An exceedingly high proportion of elderly psychiatric inpatients displayed clinically relevant MRPs in the present study, which may be explained by the multimorbidity prevalent in the study population and the associated polypharmacy. The number of drug interactions was largely in accordance with previous studies. As a novel finding, we detected that a considerable proportion of elderly psychiatric inpatients were affected by potential prescribing omissions, potentially inappropriate duplicate prescriptions, and insufficient documentation., (© 2022 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

A major proportion of people with Parkinson's disease (PwP) in Germany has written an advance directive (AD). Unfortunately, these ADs are unclear for PD-specific endpoints. We previously established consensus-based recommendations for disease-specific content of an AD in PwP. However, the implementation of those recommendations and the consulting of AD creation and modification in PwP remains to be evaluated. This study aimed to investigate the practical use of PD-specific recommendations for ADs in outpatient settings. A total of 87 physicians (45 general practitioners (GPs) and 42 neurologists, 10% response rate) answered a self-constructed semiquantitative questionnaire. The participants were asked to evaluate the suggested PD-specific recommendations for ADs and the supply of palliative care in the outpatient setting. Overall, the vast majority of treating physicians agreed on the usefulness of the newly constructed PD-specific recommendations. Consultations to discuss information about PD-specific ADs were scarce with short durations. Only 24% of participating physicians implemented the PD-specific recommendations in their daily practice. GPs and neurologists agreed on the benefit of disease-specific recommendations for ADs. In future, a more general integration of these recommendations in routine care might improve specific AD creation of PwP and advanced care planning.

Objectives: To study in vivo gray matter (GM) volumes of the nucleus basalis of Meynert (nbM) in different parkinsonian syndromes and assess their relationship with clinical variables., Methods: T1-weighted magnetic resonance images from patients with progressive supranuclear palsy (PSP, N = 43), multiple system atrophy (MSA, N = 23), Parkinson's disease (PD, N = 26), and healthy controls (HC, N = 29) were included. T1-weighted images were analyzed using a voxel-based morphometry approach implemented in the VBM8 toolbox, and nbM volumes were extracted from the spatially normalized GM images using a cyto-architectonically-defined nbM mask in stereotactic standard space. NbM volumes were compared between groups, while controlling for intracranial volume. Further, within each group correlation analyses between nbM volumes and the Mini Mental Status Examination (MMSE), Hoehn and Yahr stage, PSP Rating Scale, Unified Parkinson's Disease Rating Scale part III and Frontal Assessment Battery scores were performed., Results: Significantly lower nbM volumes in patients with PSP and PD compared to HC or patients with MSA were found. No significant correlations between MMSE and nbM volumes were detected in any of the subgroups. No significant correlations were found between clinical scores and nbM volumes in PSP or other groups., Conclusion: nbM volumes were reduced both in PD and PSP but not in MSA. The lack of significant correlations between nbM and cognitive measures suggests that other factors, such as frontal atrophy, may play a more important role than subcortical cholinergic atrophy in PSP patients. These results may indicate that other drug-targets are needed to improve cognitive function in PSP patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rogozinski, Klietz, Respondek, Oertel, Grothe, Pereira and Höglinger.)

Parkinson's disease (PD) is a progressive neurodegenerative disorder resulting in reduced health-related quality of life (HR-QoL) of people with PD (PwP) and their caregivers. Furthermore, there is an accumulating burden on caregivers of patients in advanced stages of the disease. In previous studies, motor- and non-motor-symptoms of PwP have been identified to contribute to reduced HR-QoL and an increased caregiver burden. This cross-sectional observational study aimed to study the influence of neuropsychiatric symptoms measured with the Scale for Evaluation of Neuropsychiatric Disorders in Parkinson's Disease (SEND-PD) questionnaire on the HR-QoL of PwP, as well as the caregiver burden. Analyses revealed a significant association between SEND-PD subscale mood/apathy and reduced HR-QoL in PwP, measured by the Parkinson's disease quality of life questionnaire (PDQ-8) ( p < 0.001). Furthermore, mood/apathy was significantly correlated with caregiver burden ( p = 0.001) in the multiple linear regression analysis. Hence, neuropsychiatric symptoms were found to have a profound impact on the HR-QoL of PwP, as well as on caregiver burden. Since neuropsychiatric symptoms were one of the main predictors for caregiver burden, physicians of PwP should treat these symptoms to stabilize caregiver burden, as well as HR-QoL in PwP and their caregivers.

In an industrial society, the proportion of geriatric people increases with rising age. These people are likely to use polypharmacy and experience medical emergencies. However, their emergency care can be complicated by unclear comorbidities and medication. The aim of this prospective interventional study was to assess the demand for a drug safety tool in clinical practice and to analyze whether the emergency box can improve acute care in a geriatric cohort. Therefore, emergency room (ER) doctors in a German tertiary hospital recorded the number of geriatric patients lacking medical information and its impact on diagnostics/treatment. Furthermore, the emergency box was distributed to patients on the neurological ward and their current drug safety concepts were assessed. After 6 months, we evaluated in a follow-up whether the tool was helpful in emergency cases. Our study revealed that 27.4% ( n = 28) of the patients came to the ER without their medical information, which caused a relevant delay or possible severe complications in 11.8% ( n = 12). The emergency box was perceived as easily manageable and 87.9% ( n = 109) of the participants wanted to keep it after the study. Subjectively, participants benefitted in emergencies. In conclusion, the emergency box is a cheap tool that is easy to use. It can save valuable time in emergencies and increases the safety of geriatric patients.

Parkinson's disease (PD) is a neurodegenerative disease which gives a person a high risk of becoming care-dependent. During disease progression, the amount of care concerning activities of daily living can increase, possibly resulting in transition of the people with Parkinson's disease (PwP) to a care facility. However, there is a lack of knowledge concerning the factors leading to institutionalization of PwP and the consequences for them and their informal caregivers. The aim of this cross-sectional retrospective study was to investigate reasons leading to the transition into an institutional care facility, the process of decision-making and its effects on PwP symptoms and caregiver burden. Participating PwP had to be institutionalized for at most one year after transition at study inclusion. Participants completed a range of semiquantitative questionnaires as well as the caregiving tasks questionnaire. Fourteen patient-caregiver pairs were included. PwP suffered from late-stage PD symptoms with high dependence on help, experiencing several hospitalizations before transition. Analyses revealed a significant decrease in caregiver burden and depressive symptoms of the caregivers after PwP institutionalization. Factors influencing the transition were, e.g., fear of PwP health issues and concerns about caregivers' health. This study presents new insights into the process of institutionalization and its influence on caregiver burden, including aspects for discussions of physicians with PwP and their caregivers for counselling the decision to move to institutional care.

Objective: Parkinson's disease (PD) is the second most common neurodegenerative disease in the elderly. In early stages of PD, patients typically display normal brain magnet resonance imaging (MRI) in routine screening. Advanced imaging approaches are necessary to discriminate early PD patients from healthy controls. In this study, microstructural changes in relevant brain regions of early PD patients were investigated by using quantitative MRI methods. Methods: Cerebral MRI at 3T was performed on 20 PD patients in early stages and 20 age and sex matched healthy controls. Brain relative proton density, T1, T2, and T2' relaxation times were measured in 14 regions of interest (ROIs) in each hemisphere and compared between patients and controls to estimate PD related alterations. Results: In comparison to matched healthy controls, the PD patients revealed decreased relative proton density in contralateral prefrontal subcortical area, upper and lower pons, in ipsilateral globus pallidus, and bilaterally in splenium corporis callosi, caudate nucleus, putamen, thalamus, and mesencephalon. The T1 relaxation time was increased in contralateral prefrontal subcortical area and centrum semiovale, putamen, nucleus caudatus and mesencephalon, whereas T2 relaxation time was elevated in upper pons bilaterally and in centrum semiovale ipsilaterally. T2' relaxation time did not show significant changes. Conclusion: Early Parkinson's disease is associated with a distinct profile of brain microstructural changes which may relate to clinical symptoms. The quantitative MR method used in this study may be useful in early diagnosis of Parkinson's disease. Limitations of this study include a small sample size and manual selection of the ROIs. Atlas-based or statistical mapping methods would be an alternative for an objective evaluation. More studies are necessary to validate the measurement methods for clinical use in diagnostics of early Parkinson's disease., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Klietz, Elaman, Mahmoudi, Nösel, Ahlswede, Wegner, Höglinger, Lanfermann and Ding.)

Parkinson's disease (PD) is a neurodegenerative disorder, which leads to reduced health-related quality of life (HR-QoL) and autonomy in advanced stages of the disease. Hence, people with PD (PwPD) are in need of help, which is often provided by informal caregivers, especially spouses. This might influence the relationship satisfaction in patients and their spousal caregivers. Additionally, previous studies have shown that a reduced relationship satisfaction may result in mental disorders and reduced physical health. The aim of this study is to identify factors influencing PwPD and their caregivers' relationship satisfaction in a cross-sectional observational study. Analyses revealed an overall satisfying relationship, measured by the Quality of Marriage Index, in PwPD ( n = 84) and their caregivers ( n = 79). Relationship satisfaction in PwPD mildly decreased with reduced HR-QoL and more severe depressive symptoms. Reduced relationship satisfaction in caregivers was significantly associated with decreased HR-QoL, higher caregiver burden, more severe depressive symptoms and increased neuropsychiatric symptoms in PwPD. Further studies are needed to investigate the influence of the identified factors over time and if relationship satisfaction has a reciprocal impact on caregiver burden, HR-QoL as well as mental and physical health.

DYT-THAP1 dystonia (formerly DYT6) is an adolescent-onset dystonia characterized by involuntary muscle contractions usually involving the upper body. It is caused by mutations in the gene THAP1 encoding for the transcription factor Thanatos-associated protein (THAP) domain containing apoptosis-associated protein 1 and inherited in an autosomal-dominant manner with reduced penetrance. Alterations in the development of striatal neuronal projections and synaptic function are known from transgenic mice models. To investigate pathogenetic mechanisms, human induced pluripotent stem cell (iPSC)-derived medium spiny neurons (MSNs) from two patients and one family member with reduced penetrance carrying a mutation in the gene THAP1 (c.474delA and c.38G > A) were functionally characterized in comparison to healthy controls. Calcium imaging and quantitative PCR analysis revealed significantly lower Ca 2+ amplitudes upon GABA applications and a marked downregulation of the gene encoding the GABA A receptor alpha2 subunit in THAP1 MSNs indicating a decreased GABAergic transmission. Whole-cell patch-clamp recordings showed a significantly lower frequency of miniature postsynaptic currents (mPSCs), whereas the frequency of spontaneous action potentials (APs) was elevated in THAP1 MSNs suggesting that decreased synaptic activity might have resulted in enhanced generation of APs. Our molecular and functional data indicate that a reduced expression of GABA A receptor alpha2 subunit could eventually lead to limited GABAergic synaptic transmission, neuronal disinhibition, and hyperexcitability of THAP1 MSNs. These data give pathophysiological insight and may contribute to the development of novel treatment strategies for DYT-THAP1 dystonia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Staege, Kutschenko, Baumann, Glaß, Henkel, Gschwendtberger, Kalmbach, Klietz, Hermann, Lohmann, Seibler and Wegner.)

Progressive supranuclear palsy (PSP) is an atypical Parkinson syndrome with axial akinetic-rigid symptoms, early postural instability, and ocular motor impairments. Patients experience a rapid loss of autonomy and care dependency; thus, caregivers must assist in the activities of daily living early in the course of the disease. Caregiver burden is an extremely important factor in disease management. However, there are no specific questionnaires for assessment of caregiver burden in PSP. This study aims to validate the Parkinson's disease caregiver burden questionnaire (PDCB) as a specific measure of caregiver burden in PSP. PSP patients were assessed by the PSP rating scale, PSP quality-of-life questionnaire (PSP-QoL), Montreal cognitive assessment test (MoCA), and geriatric depression scale (GDS-15). Caregivers filled out the short form 36-health survey, GDS-15, PDCB, and the caregiver burden inventory (CBI). 22 patient caregiver pairs completed the study. PDCB showed a highly significant correlation with the CBI (r 0.911; p < 0.001). Internal reliability of the PDCB measured by Cronbach's alpha was favourable at 0.803. These data support the specificity of the PDCB in PSP caregivers. Future studies with larger sample sizes of PSP patients and caregivers and a multicentric longitudinal design should be performed to gain further insight of caregiver burden in PSP., Competing Interests: The authors declare that they have no conflicts of interest to report., (Copyright © 2021 Martin Klietz et al.)