Abstract Misfolding and aggregation of alpha-synuclein (αSyn) play a key role in the pathophysiology of Parkinson’s disease (PD). Despite considerable advances in diagnostics, an early and differential diagnosis of PD still represents a major challenge. We innovated the immuno-infrared sensor (iRS) platform for measuring αSyn misfolding. We analyzed cerebrospinal fluid (CSF) from two cohorts comprising PD cases, atypical Parkinsonian disorders, and disease controls. We obtained an AUC of 0.90 (n = 134, 95% CI 0.85–0.96) for separating PD/MSA from controls by determination of the αSyn misfolding by iRS. Using two thresholds divided individuals as unaffected/affected by misfolding with an intermediate area in between. Comparing the affected/unaffected cases, controls versus PD/MSA cases were classified with 97% sensitivity and 92% specificity. The spectral data revealed misfolding from an α-helical/random-coil αSyn in controls to β-sheet enriched αSyn in PD and MSA cases. Moreover, a first subgroup analysis implied the potential for patient stratification in clinically overlapping cases. The iRS, directly measuring all αSyn conformers, is complementary to the αSyn seed-amplification assays (SAAs), which however only amplify seeding competent conformers.

Parkinson’s disease (PD) is characterized by hypokinetic motor symptoms, tremor, and various non-motor symptoms with frequent fluctuations of symptoms in advanced disease stages. Invasive therapies, such as deep brain stimulation (DBS), ablative therapies, and continuous subcutaneous or intrajejunal delivery of dopaminergic drugs via pump therapies are available for the management of this complex motor symptomatology and may also impact non-motor symptoms. The recent update of the clinical guideline on PD by the German Neurological Society (Deutsche Gesellschaft für Neurologie e.V.; DGN) offers clear guidance on the indications and applications of these treatment options. The guideline committee formulated diagnostic questions for invasive therapies and structured them according to the PICOS framework (Population–Intervention–Comparisons–Outcome–Studies). A systematic literature review was conducted. Questions were addressed using the findings from the literature review and consented by the guideline committee. Specific recommendations are given regarding (i) the optimal timing for starting invasive therapies, (ii) the application of DBS, (iii) the use of pump therapies in advanced PD, (iv) the indications for ablative procedures, and (iv) selecting the most appropriate therapy according to individual patient characteristics. This review is an adapted excerpt of the chapters on the use of invasive therapies in PD of the novel German guideline on PD. Clear recommendations on the use of treatment options for advanced PD are provided.

BACKGROUND:Patients with Progressive Supranuclear Palsy (PSP) suffer from several neuropsychological impairments. These mainly affect the frontal lobe and subcortical brain structures. However, a scale for the assessment of cognitive and neuropsychiatric disability in PSP is still missing. OBJECTIVES:To create and validate a new scale for cognitive and neuropsychiatric impairment in PSP. METHODS:The Short Cognitive and Neuropsychiatric (ShoCo) scale was developed containing five items (bradyphrenia, apathy, aphasia, dysexecution and disinhibition). Each item can be categorized into 0 = no deficit, 1 = mild deficit, 2 = moderate deficit and 3 = severe deficit. The total score includes 15 points, 0 meaning no deficit and 15 severe deficits. Cross-sectional and longitudinal data from 201 baseline and 71 follow up patients were analyzed. RESULTS:Baseline ShoCo scale results were 5.9 ± 2.9. No significant differences between patients with Richardson syndrome (PSP-RS) and variants (vPSP) could be detected in the PSP-ShoCo scale scores (PSP-RS 6.1 ± 3.0, n = 160, vPSP 5.1 ± 2.6, n = 41, P = 0.057). The scale showed good correlation with established scores (eg, Montreal cognitive assessment r = -0.535, P = 0.001). The ShoCo scale showed significant annualized change within the PSP-RS patients (baseline 6.2 ± 2.9, follow up 6.9 ± 3.1, annualized diff. 1.0 ± 3.1, n = 57, P = 0.022). CONCLUSIONS:The ShoCo scale seems a promising and valid tool to measure specific neuropsychological disabilities of PSP patients in clinical routine and research.

Parkinson′s disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA) are characterized by pathological aggregation of misfolded alpha-synuclein (αSyn) in the central and peripheral nervous systems. Seed amplification assays (SAAs) can detect misfolded αSyn in cerebrospinal fluid (CSF), allowing a more precise biological classification of these diseases. Translating biomarker-based diagnostics to blood represents a crucial milestone to democratize access to molecular testing, as blood sampling is minimally invasive and widely scalable. However, current blood-based SAA approaches require extensive sample preprocessing, which introduces variability and has yielded inconsistent results. Here, we present the immuno-infrared-sensor (iRS) platform, which detects misfolded αSyn directly in blood serum without sample preprocessing and without amplification. The iRS measures the secondary-structure distribution of αSyn by distinguishing α-helical/random-coil monomers from β-sheet-rich oligomers and fibrils. This conformational distribution reflects disease-associated structural changes in blood and provides information beyond the binary readout of SAAs. In a combined cohort (n = 127) consisting of 74 individuals with synucleinopathies (PD, DLB, MSA and isolated rapid eye movement sleep behavior disorder (iRBD)) and 53 controls, the assay achieved a receiver operating characteristic area under the curve (ROC AUC) of 0.94 (95% confidence interval (CI), 0.88–0.99), with 88% sensitivity and 89% specificity in serum using a dual-threshold classification that categorized individuals as controls (no misfolding, green), at risk (low misfolding, yellow) or diseased (high misfolding, red). By extending the iRS platform from CSF to blood serum, this study demonstrates αSyn misfolding as a promising blood-based structural biomarker for synucleinopathies. The iRS assay provides a broadly applicable platform technology for more precise biological classification, disease monitoring and assessment of drug response for PD in peripheral blood. ### Competing Interest Statement Klaus Gerwert is the founder and CEO of betaSENSE GmbH. The remaining authors declare no competing interests. ### Funding Statement This research was funded by the Center for Protein Diagnostics (ProDi) and the Ministry of Culture and Science of North Rhine-Westphalia. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of Landesaerztekammer Hessen gave ethical approval for this work (approval no. FF89/2008 and FF38/2016) I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors

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.

In addition to their motor symptoms, almost all Parkinson’s disease patients report non-motor symptoms (NMS) and, in the later course of the disease, non-motor fluctuations as well. These NMS encompass e.g. neuropsychiatric, gastrointestinal, urogenital, cardiovascular symptoms and pain. For a long time, these symptoms received no or at best very little attention, but there is a growing trend towards their recognition and treatment. Despite this progress, significant gaps remain, particularly due to the sometimes-limited expertise among neurologists regarding these symptoms. The clinical need to consequently treat these NMS raises the question of whether Movement Disorder specialists should and can address them sufficiently or if additional consultant physicians have to be enrolled. Therefore, our objective is to establish benchmarking criteria to outline a potential way forward. Ideally, Movement Disorder specialists should take on greater responsibility when treating non-motor PD symptoms, integrating diagnostic and therapeutic pathways from other medical disciplines where feasible.

Die stationäre Parkinson-Komplextherapie (PKT) wurde 2022 in Deutschland mehr als 15.000-mal angewendet. Diese Zahl nimmt ebenso zu wie die Parkinson-Krankheit (PK), die in Deutschland gut 400.000 Personen betrifft und zu 100.000 verlorenen gesunden Lebensjahren führt. In den letzten Jahren wurden mehrere Beobachtungsstudien zur Wirksamkeit der multidisziplinären PKT durchgeführt. Zusammenfassung und Diskussion der Evidenz zu Wesen, Nutzen und Potenzialen der PKT Es erfolgte ein narratives Review selektierter empirischer Befunde. Die häufig 2‑ bis 3‑wöchige PKT zielt auf den Erhalt der Lebensqualität von Personen mit PK ab. Krankheitssymptome und Alltagsfunktionen werden gemeinsam durch pharmakologische Strategien und aktivierende Therapien verbessert (Physiotherapie, Ergotherapie, Logopädie, körperliches Training, künstlerische Therapien). Die PKT ist eine nützliche Maßnahme, um Krisensituationen im Krankheitsverlauf zu vermeiden oder abzumildern. Acht Beobachtungsstudien (n = 1246) weisen eine gute Wirksamkeit nach (insgesamt durchschnittliche Verbesserung um 7,8 Punkte auf der International Parkinson and Movement Disorder Society Unified Parkinson’s Disease Rating Scale III [MDS-UPDRS III]). Für nachhaltige Effekte auf die Lebensqualität muss der Transfer von Übungen in den Alltag durch intensive und spezialisierte ambulante Therapien sichergestellt werden. Dieser Transfer kann im Idealfall zukünftig durch Parkinson-Netzwerke und digitale Technologien unterstützt werden. Es bestehen Entwicklungspotenziale bei der Standardisierung, Patientenauswahl und Qualitätssicherung der PKT sowie bei der Einbettung in Versorgungsstrukturen wie Parkinson-Netzwerke. Offene wissenschaftliche Fragen umfassen die genauere Definition der Zielgruppe und den höherwertigen Nachweis der kurz- und langfristigen Wirksamkeit.

BACKGROUND:The inpatient Parkinson's disease multimodal complex treatment (PD-MCT) was applied more than 15,000 times in 2022, in Germany. This number is increasing as is Parkinson's disease (PD), which affects more than 400,000 people in Germany and leads to 100,000 disability-adjusted life years. In recent years, several observational studies have been conducted on the effectiveness of this kind of multidisciplinary care. OBJECTIVE:To summarize and discuss the evidence on the nature, benefits and potential of PD-MCT. METHODS:A narrative review of selected empirical findings was carried out. RESULTS:The PD-MCT frequently lasts for 2-3 weeks and aims to maintain the quality of life of people with PD. Disease symptoms and activities of daily living are jointly improved by pharmacological strategies and activating therapies (physiotherapy, occupational therapy, speech and language therapy, physical training, art therapy). The PD-MCT is a useful measure to avoid or mitigate crisis situations in the course of the disease. A total of eight observational studies (n = 1246) have shown good effectiveness with a total mean improvement of the International Parkinson and Movement Disorder Society unified Parkinson's disease rating scale III (MDS-UPDRS III) by 7.8 points. The transfer of effects into everyday life through intensive and specialized community-based care must be ensured in order to achieve sustained effects on the quality of life. Ideally, this transfer can be supported by integrated PD networks and digital technologies in the future. CONCLUSION:There is potential for development in the standardization, patient selection and quality assurance of PD-MCT as well as in the embedding in care structures such as PD networks. Open research questions include a precise definition of the target group and higher quality evidence of short-term and long-term effectiveness.

Background:Vagal atrophy is a hallmark of Parkinson's disease (PD) and has been found to be associated with autonomic dysfunction, while analyses of the vagus nerve (VN) in atypical Parkinsonian syndromes (APS) have not yet been performed. We here investigate the characteristics of the VN in multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) and, in a second step, its potential as a possible biomarker for orthostatic dysregulation. Objectives:The aim was to compare the VN pathology in MSA and PSP with healthy individuals and patients with PD as a differentiating factor and to further analyse the correlation of the VN with clinical parameters and cardiovascular response. Design:We conducted a monocentric, cross-sectional cohort study in 41 APS patients and compared nerve ultrasound (NUS) parameters with 90 PD patients and 39 healthy controls. Methods:In addition to a detailed neurological history and examination, several clinical severity and motor scores were obtained. Autonomic symptoms were reported in the Scales for Outcomes in Parkinson's Disease - Autonomic questionnaire. Further scores were used to detect other non-motor symptoms, quality of life and cognition. Additionally, we performed a head up tilt test (HUTT) and NUS of the VN. We conducted correlation analyses of the VN cross-sectional area (CSA) with clinical scores and the heart rate and blood pressure variability parameters of the HUTT. Results:The examination demonstrated a high prevalence of abnormal autonomic response in both MSA (90%) and PSP (80%). The VN CSA correlated with spectral parameters of the HUTT, which are associated with sympatho-vagal imbalance. In addition, the CSA of the VN in patients with PD and PSP were significantly smaller than in healthy controls. In MSA, however, there was no marked vagal atrophy in comparison. Conclusion:The occurrence of autonomic dysfunction was high in MSA and PSP, which underlines its impact on these syndromes. Our findings indicate a connection between vagal pathology and autonomic dysfunction and might contribute to a better comprehension of APS. To further evaluate the clinical relevance and the VN as a possible marker of autonomic dysfunction in APS, prospective longitudinal observations are necessary.

Estimates of the spectrum and frequency of pathogenic variants in Parkinson's disease (PD) in different populations are currently limited and biased. Furthermore, although therapeutic modification of several genetic targets has reached the clinical trial stage, a major obstacle in conducting these trials is that PD patients are largely unaware of their genetic status and, therefore, cannot be recruited. Expanding the number of investigated PD-related genes and including genes related to disorders with overlapping clinical features in large, well-phenotyped PD patient groups is a prerequisite for capturing the full variant spectrum underlying PD and for stratifying and prioritizing patients for gene-targeted clinical trials. The Rostock Parkinson's disease (ROPAD) study is an observational clinical study aiming to determine the frequency and spectrum of genetic variants contributing to PD in a large international cohort. We investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap in a group of 12 580 PD patients from 16 countries [62.3% male; 92.0% White; 27.0% positive family history (FH+), median age at onset (AAO) 59 years] using a next-generation sequencing panel. Altogether, in 1864 (14.8%) ROPAD participants (58.1% male; 91.0% White, 35.5% FH+, median AAO 55 years), a PD-relevant genetic test (PDGT) was positive based on GBA1 risk variants (10.4%) or pathogenic/likely pathogenic variants in LRRK2 (2.9%), PRKN (0.9%), SNCA (0.2%) or PINK1 (0.1%) or a combination of two genetic findings in two genes (similar to 0.2%). Of note, the adjusted positive PDGT fraction, i.e. the fraction of positive PDGTs per country weighted by the fraction of the population of the world that they represent, was 14.5%. Positive PDGTs were identified in 19.9% of patients with an AAO <= 50 years, in 19.5% of patients with FH+ and in 26.9% with an AAO <= 50 years and FH+. In comparison to the idiopathic PD group (6846 patients with benign variants), the positive PDGT group had a significantly lower AAO (4 years, P = 9 x 10(-34)). The probability of a positive PDGT decreased by 3% with every additional AAO year (P = 1 x 10(-35)). Female patients were 22% more likely to have a positive PDGT (P = 3 x 10(-4)), and for individuals with FH+ this likelihood was 55% higher (P = 1 x 10(-14)). About 0.8% of the ROPAD participants had positive genetic testing findings in parkinsonism-, dystonia/dyskinesia- or dementia-related genes. In the emerging era of gene-targeted PD clinical trials, our finding that similar to 15% of patients harbour potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. Thus, the insights from the ROPAD study allow for data-driven, differential genetic counselling across the spectrum of different AAOs and family histories and promote a possible policy change in the application of genetic testing as a routine part of patient evaluation and care in PD.

Background: The inpatient Parkinson’s Disease Multimodal Complex Treatment (PD-MCT) is an important therapeutical approach to improving gait and activities of daily living (ADL) of people with PD (PwP). Wearable device-based parameters (DBP) are new options for specific gait analyses toward individualized treatments. Objectives: We sought to identify predictors of perceived ADL benefit taking clinical scores and DBP into account. Additionally, we analyzed DBP and clinical scores before and after PD-MCT. Design: Exploratory observational cohort study. Methods: Clinical scores and DBP of 56 PwP (mean age: 66.3 years, median Hoehn and Yahr (H&Y) stage: 2.5) were examined at the start and the end of a 14-day inpatient PD-MCT in a German University Medical Center. Participants performed four straight walking tasks under single- and dual-task conditions for gait analyses. Additionally, clinical scores of motor and nonmotor functions and quality of life (QoL) were assessed. Using dichotomized data of change in Movement Disorders Society Unified Parkinson’s Disease Rating Scale Part II (MDS-UPDRS II) as a dependent variable and clinical and DBP as independent variables, a binomial logistic regression model was implemented. Results: Young age, high perceived ADL impairment at baseline, high dexterity skills, and a steady gait were significant predictors of ADL benefit after PD-MCT. DBP like gait speed, number of steps, step time, stance time, and double limb support time were improved after PD-MCT. In addition, motor functions (e.g., MDS-UPDRS III and IV), QoL, perceived ADL (MDS-UPDRS II), and experience of nonmotor functions (MDS-UPDRS I) improved significantly. Conclusion: The logistic regression model identified a group of PwP who had the most probable perceived ADL benefit after PD-MCT. Additionally, gait improved toward a faster and more dynamic gait. Using wearable technology in context of PD-MCT is promising to offer more personalized therapeutical concepts. Trial registration: German Clinical Trial Register, https://drks.de ; DRKS00020948 number, 30 March 2020, retrospectively registered.

Background Parkinson's disease (PD) is a neurodegenerative disease that leads to progressive disability. Cost studies have mainly explored the early stages of the disease, whereas late-stage patients are underrepresented. Objective The aim is to evaluate the resource utilization and costs of PD management in people with late-stage disease. Methods The Care of Late-Stage Parkinsonism (CLaSP) study collected economic data from patients with late-stage PD and their caregivers in five European countries (France, Germany, the Netherlands, UK, Sweden) in a range of different settings. Patients were eligible to be included if they were in Hoehn and Yahr stage >3 in the on state or Schwab and England stage at 50% or less. In total, 592 patients met the inclusion criteria and provided information on their resource utilization. Costs were calculated from a societal perspective for a 3-month period. A least absolute shrinkage and selection operator approach was utilized to identify the most influential independent variables for explaining and predicting costs. Results During the 3-month period, the costs were 20,573 (France), 19,959 (Germany), 18,319 (the Netherlands), 25,649 (Sweden), and 12,156 (UK). The main contributors across sites were formal care, hospitalization, and informal care. Gender, age, duration of the disease, Unified Parkinson's Disease Rating Scale 2, the EQ-5D-3L, and the Schwab and England Scale were identified as predictors of costs. Conclusion Costs in this cohort of individuals with late-stage PD were substantially higher compared to previously published data on individuals living in earlier stages of the disease. Resource utilization in the individual sites differed in part considerably among these three parameters mentioned. (c) 2024 The Authors. 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.

Background Increasing evidence indicates a higher prevalence of polyneuropathy (PNP) in Parkinson's disease (PD). However, the involvement of large fiber neuropathy in PD still remains poorly understood. Given the lack of longitudinal data, we investigated the course of PNP associated with PD. Methods In total, 41 PD patients underwent comprehensive clinical evaluation including motor and non-motor assessments as well as nerve conduction studies at baseline and at 2 years of follow-up. The definition of PNP was based on electrophysiological standard criteria. Common causes of PNP were excluded. Results At baseline, PNP was diagnosed in 65.85% of PD patients via electroneurography. Patients with PNP presented with higher age (p = 0.019) and PD motor symptom severity (UPDRS III; p < 0.001). Over the course of 2 years, PNP deteriorated in 21.95% of cases, and 26.83% remained without PNP. Deterioration of nerve amplitude was most prevalent in the median sensory nerve affecting 57.58% of all PD cases with an overall reduction of median sensory nerve amplitude of 45.0%. With regard to PD phenotype, PNP progression was observed in 33.33% of the tremor dominant and 23.81% of the postural instability/gait difficulties subtype. Decrease of sural nerve amplitude correlated with lower quality of life (PDQ-39, p = 0.037) and worse cognitive status at baseline (MoCA, p = 0.042). Conclusion The study confirms the high PNP rate in PD, and demonstrates a significant electrophysiological progression also involving nerves of the upper extremities. Longitudinal studies with larger cohorts are urgently needed and should elucidate the link between PD and PNP with the underlying pathomechanisms.

Zusammenfassung Hintergrund Die Parkinson-Krankheit ist als weltweit am schnellsten zunehmende neurodegenerative Erkrankung gesellschaftlich hoch relevant. Für eine erfolgreiche Behandlung ist die aktive Beteiligung der Patient*innen erforderlich. Patientenschulen werden bei vielen chronischen Erkrankungen wie Diabetes erfolgreich eingesetzt und könnten auch Menschen mit der Parkinson-Krankheit Fähigkeiten vermitteln, besser mit der Krankheit umzugehen und an Therapieentscheidungen teilzunehmen. Material und Methoden Um die Implementierung eines Konzepts für eine Patientenschule für Menschen mit der Parkinson-Krankheit vorzubereiten, wurde ein strukturiertes Konsensusverfahren durchgeführt und ein Pilotprojekt formativ evaluiert. Das strukturierte Konsensusverfahren mit deutschlandweit rekrutierten Expert*innen gliederte sich in eine 1. und 2. Onlinebefragung sowie eine abschließende Konsensuskonferenz. Die formative Evaluation erfolgte durch drei Fokusgruppen. Die Transkripte dieser Gruppeninterviews wurden computergestützt mittels inhaltlich-strukturierender qualitativer Inhaltsanalyse ausgewertet. Ergebnisse In dem Konsensusverfahren konnten 59 Aussagen konsentiert werden, insbesondere zu den Inhalten einer Patientenschule und zu einer Gruppengröße von 6 bis 8 Personen. Lediglich zwei Aussagen wurden nicht konsentiert. Aus der formativen Evaluation waren eine tendenziell positive Haltung gegenüber einem digitalen Schulungsformat und eine sehr positive Bewertung der Inhalte ableitbar. Diskussion Insgesamt konnten wichtige Empfehlungen für eine Patientenschule formuliert werden. Zu den Themen Format, Einschlusskriterien, Gruppenzusammensetzung und Einbeziehung von Angehörigen ist dagegen eine weitere Betrachtung erforderlich.

INTRODUCTION:In 2023, the German Society of Neurology published a new guideline on Parkinson's disease. An important section dealt with PD care concepts, which represent a particularly dynamic field of PD research, including their implementation in clinical practice. Parkinson's disease is the second most common age-associated neurodegenerative disease. Current estimates of the number of cases in the population describe a significant increase in prevalence in Germany by 2030 with higher proportions in rural areas, which also have a lack of sufficient PD care resources. RECOMMENDATIONS:In comparison with other international guidelines, which have so far mentioned palliative care and Parkinson's nurses in particular, the German S2k guideline expands the recommended concepts of PD care to include PD day clinics, inpatient complex treatment, and PD networks. CONCLUSION:Concepts of PD care guidelines are necessary because of the complex and rapidly evolving field of PD care provision. If applied appropriately, the potential for optimized care can be exploited and both the patient burden and the economic burden can be reduced. Given that modern care concepts have so far only been applied in a few regions, it is often impossible to generate broad evidence-based data, so that the evaluation of PD care concepts is partly dependent on expert opinion.

Abstract Background Numerous studies reported a higher prevalence of polyneuropathy (PNP) in patients with Parkinson’s disease (PD) compared to the general population. Importantly, PNP symptoms can aggravate both motor and sensory disturbances in PD patients and negatively impact the disease course. Recent analyses indicate distinct PNP patterns in PD. Main text This review aims to provide an overview of the current insights into etiological factors, diagnostic methods, and management strategies of large fiber neuropathy in PD. Despite the higher prevalence, the causes of PNP in PD are still not fully understood. A genetic predisposition can underlie PNP onset in PD. Main research attention is focused on long-term levodopa exposure which is suggested to increase PNP risk by depletion of methylation cofactors such as vitamin B12 and accumulation of homocysteine that altogether can alter peripheral nerve homeostasis. Beyond a potential “iatrogenic” cause, alpha-synuclein deposition has been detected in sural nerve fibers that could contribute to peripheral neuronal degeneration as part of the systemic manifestation of PD. Whereas mild axonal sensory PNP predominates in PD, a considerable proportion of patients also show motor and upper limb nerve involvement. Intriguingly, a correlation between PNP severity and PD severity has been demonstrated. Therefore, PNP screening involving clinical and instrument-based assessments should be implemented in the clinical routine for early detection and monitoring. Given the etiological uncertainty, therapeutic or preventive options remain limited. Vitamin supplementation and use of catechol-O-methyltransferase-inhibitors can be taken into consideration. Conclusion PNP is increasingly recognized as a complicating comorbidity of PD patients. Long-term, large-scale prospective studies are required to elucidate the causative factors for the development and progression of PD-associated PNP to optimize treatment approaches. The overall systemic role of “idiopathic” PNP in PD and a putative association with the progression of neurodegeneration should also be investigated further.

Proteomic studies using mass spectrometry (MS)-based quantification are a main approach to the discovery of new biomarkers. However, a number of analytical conditions in front and during MS data acquisition can affect the accuracy of the obtained outcome. Therefore, comprehensive quality assessment of the acquired data plays a central role in quantitative proteomics, though, due to the immense complexity of MS data, it is often neglected. Here, we address practically the quality assessment of quantitative MS data, describing key steps for the evaluation, including the levels of raw data, identification and quantification. With this, four independent datasets from cerebrospinal fluid, an important biofluid for neurodegenerative disease biomarker studies, were assessed, demonstrating that sample processing-based differences are already reflected at all three levels but with varying impacts on the quality of the quantitative data. Specifically, we provide guidance to critically interpret the quality of MS data for quantitative proteomics. Moreover, we provide the free and open source quality control tool MaCProQC, enabling systematic, rapid and uncomplicated data comparison of raw data, identification and feature detection levels through defined quality metrics and a step-by-step quality control workflow.