Guideline "Parkinson's disease" of the German Society of Neurology (Deutsche Gesellschaft für Neurologie): concepts of care.

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.

[Multidisciplinary Complex Treatment of Parkinson's disease : Cornerstone of an individualized treatment]. / Multidisziplinäre Komplextherapie der Parkinson-Krankheit : Eckpfeiler einer individualisierten Behandlung.

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.

Care of Late-Stage Parkinsonism: Resource Utilization of the Disease in Five European Countries.

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. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

[How the implementation of a school for people with Parkinson's disease can succeed-Results of a consensus study and a formative evaluation]. / Wie die Umsetzung einer Schule für Menschen mit Parkinson-Krankheit gelingen kann ­ Ergebnisse eines Konsensusverfahrens und einer formativen Evaluation.

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.

The comorbidity and co-medication profile of patients with progressive supranuclear palsy.

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.

Inpatient care of neuromyelitis optica spectrum disorder in Germany: Nationwide analysis from 2010 to 2021.

Background: Despite tremendous development in the treatment of neuromyelitis optica spectrum disorder (NMOSD), less is known about the characteristics of hospitalized patients and inpatient care utilization. Objective: To investigate the development of inpatient NMOSD case numbers and implemented immunotherapies in the last decade in Germany. Methods: We conducted a nationwide retrospective study using an administrative database of all hospitalized NMOSD patients between 2010 and 2021. We evaluated yearly data on case numbers, demographics, treatment regimens, and seasonal variations of apheresis therapy as a surrogate marker of severe relapse incidence. Results: During the observational period case number of inpatients substantially increased (2010:n = 463, 2021:n = 992). The mean age was 48.1 ± 2.5 years (74% females). The pooled yearly rate of plasmapheresis/immunoadsorption was 14% (95% CI [13-15%]), without seasonal variations. Its application peaked in 2013 (18%, 95% CI [15-21%]) with decreasing trend since. Predominant immunotherapy was rituximab (40%, 95% CI [34-45%]), followed by tocilizumab (4%, 95% CI [3-5%]) since 2013 and eculizumab (4%, 95% CI [3-5%]) since 2020. Inpatient mortality ranged between 0% and 1% per year. Conclusions: Inpatient case numbers of NMOSD substantially increased during the past decade, probably reflecting improving disease awareness. In parallel with the administration of highly effective therapies rate of apheresis therapies decreased. A stable apheresis rate over the year makes seasonal variations of the steroid-refractive relapses unlikely.

Significance of clinical symptoms and red flags in early differential diagnosis of Parkinson's disease and atypical Parkinsonian syndromes.

The clinical presentation of Parkinson's disease and atypical Parkinsonian syndromes is often heterogeneous. Additional diagnostic procedures including brain imaging and biomarker analyses can help to appreciate the various syndromes, but a precise clinical evaluation and differentiation is always necessary. To better assess the relevance of distinct clinical symptoms that arose within 1 year of disease manifestation and evaluate their indicative potential for an atypical Parkinsonian syndrome, we conducted a modified Delphi panel with seven movement disorder specialists. Five different topics with several clinical symptom items were discussed and consensus criteria were tested. This resulted in distinct symptom patterns for each atypical Parkinsonian syndrome showing the multitude of clinical involvement in each neurodegenerative disease. Strongly discriminating clinical signs were few and levels of indication were variable. A prospective validation of the assessments made is needed. This demonstrates that both clinical evaluation and elaborate additional diagnostic procedures are needed to achieve a high diagnostic standard.

Data-driven subtyping of Parkinson's disease: comparison of current methodologies and application to the Bochum PNS cohort.

Considerable efforts have been made to better describe and identify Parkinson's disease (PD) subtypes. Cluster analyses have been proposed as an unbiased development approach for PD subtypes that could facilitate their identification, tracking of progression, and evaluation of therapeutic responses. A data-driven clustering analysis was applied to a PD cohort of 114 subjects enrolled at St. Josef-Hospital of the Ruhr University in Bochum (Germany). A wide spectrum of motor and non-motor scores including polyneuropathy-related measures was included into the analysis. K-means and hierarchical agglomerative clustering were performed to identify PD subtypes. Silhouette and Calinski-Harabasz Score Elbow were then employed as supporting evaluation metrics for determining the optimal number of clusters. Principal Component Analysis (PCA), analysis of variance (ANOVA), and analysis of covariance (ANCOVA) were conducted to determine the relevance of each score for the clusters' definition. Three PD cluster subtypes were identified: early onset mild type, intermediate type, and late-onset severe type. The between-cluster analysis consistently showed highly significant differences (P < 0.01), except for one of the scores measuring polyneuropathy (Neuropathy Disability Score; P = 0.609) and Levodopa dosage (P = 0.226). Parkinson's Disease Questionnaire (PDQ-39), Non-motor Symptom Questionnaire (NMSQuest), and the MDS-UPDRS Part II were found to be crucial factors for PD subtype differentiation. The present analysis identifies a specific set of criteria for PD subtyping based on an extensive panel of clinical and paraclinical scores. This analysis provides a foundation for further development of PD subtyping, including k-means and hierarchical agglomerative clustering.Trial registration: DRKS00020752, February 7, 2020, retrospectively registered.

Quality Control-A Stepchild in Quantitative Proteomics: A Case Study for the Human CSF Proteome.

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.

Vagal cross-sectional area correlates with parasympathetic dysfunction in Parkinson's disease.

The aim of this prospective study was to investigate autonomic function in Parkinson's disease with a multidimensional approach including clinical evaluation tools, head-up tilt test and morphological studies of the vagus nerve. Head-up tilt test parameters including high frequency power of the heart frequency interval, the ratio of low frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval) to the high frequency and low frequency power of systolic blood pressure were used to evaluate parasympathetic, cardiac sympathetic and vasomotor sympathetic functions, respectively, in 80 patients with Parkinson's disease. We examined the cross-sectional area of the vagus nerves bilaterally using nerve ultrasound and compared mean values with a control group of healthy subjects (n = 40) as well as patients with chronic inflammatory demyelinating polyneuropathy (n = 76). The cross-sectional area of right/left vagus nerve of Parkinson's patients was significantly lower compared to the right/left vagus nerve of the control group and of chronic demyelinating polyneuropathy patients. Furthermore, the cross-sectional area of the right vagus nerve was significantly larger from the one of the left vagus nerve for all groups. Based on tilt test, 43 patients (disease duration 7 ± 5, age at evaluation 71 ± 9, Hoehn and Yahr score 2.8 ± 8) were diagnosed with autonomic dysfunction (orthostatic hypertension n = 11, chronotropic incompetence n = 31, postural orthostatic tachycardia syndrome n = 1). Patients with orthostatic hypotension showed significantly higher Unified Parkinson's Disease Rating Scale-III values than those with chronotropic incompetence. The cross-sectional area of the vagus nerve correlated inversely with heart rate in rest and supine position and positively with tilt test parameters representing parasympathetic modulation through vagal activity [high frequency power of the distance between two consecutive R waves in electrocardiogram (RR interval)] at rest. We demonstrate for the first time that morphological characteristics of the vagus nerve correlate with parameters of parasympathetic function from the spectral analysis of cardiovascular parameters in tilt test for Parkinson's patients. This correlation reveals the impact of the atrophy of vagal atrophy for autonomic function in Parkinson's disease. Nerve ultrasound of the vagus nerve could potentially be used as an adjunct to tilt table examination to diagnose autonomic dysfunction.

COVID-19 outcomes in hospitalized Parkinson's disease patients in two pandemic waves in 2020: a nationwide cross-sectional study from Germany.

BACKGROUND: The individualized clinical and public health management of the COVID-19 pandemic have changed over time, including care of people with PD. The objective was to investigate whether in-hospital COVID-19 outcomes and hospital care utilization of people with PD differed between the first two pandemic waves (W) 2020 in Germany. METHODS: We conducted a nationwide cross-sectional study of inpatients with confirmed COVID-19 and PD between March 1 and May 31 (W1), and October 1 and December 31 (W2), 2020 and 2019, using an administrative database. Outcomes were in-hospital mortality, ICU admission rate, change in hospital care utilization, demographical data, PD clinical characteristics, and selected comorbidities. Differences were assessed between waves, PD/non-PD groups, and years. RESULTS: We identified 2600 PD COVID-19 inpatients in W2 who in total showed higher in-hospital mortality rates and lower ICU admission rates, compared to both W1 (n = 775) and W1/W2 non-PD COVID-19 inpatients (n = 144,355). Compared to W1, W2 inpatients were more long-term care-dependent, older, more of female sex, and had less advanced disease. During both waves, PD inpatients were older, more frequently male and long-term care-dependent, and showed more risk comorbidities than non-PD COVID-19 inpatients. Decreases in hospital care utilization were stronger than average for PD inpatients but relatively weaker during W2. Non-COVID-19 PD inpatients showed poorer in-hospital outcomes in 2020 than in 2019 with better outcomes during W2. CONCLUSIONS: In-hospital COVID-19 outcomes and hospital care utilization of PD patients in Germany differed between the two pandemic waves in 2020 with increased in-hospital mortality for PD COVID-19. Overall hospital care utilization for PD was increased during W2. TRIAL REGISTRATION: No trial registration or ethical approval was required because data were publicly available, anonymized, and complied with the German data protection regulations.

SARS-CoV-2, COVID-19 and Neurodegeneration.

The COVID-19 pandemic continues to affect many areas of our daily life [...].

Parkinson's disease multimodal complex treatment improves gait performance: an exploratory wearable digital device-supported study.

BACKGROUND: Wearable device-based parameters (DBP) objectively describe gait and balance impairment in Parkinson's disease (PD). We sought to investigate correlations between DBP of gait and balance and clinical scores, their respective changes throughout the inpatient multidisciplinary Parkinson's Disease Multimodal Complex Treatment (PD-MCT), and correlations between their changes. METHODS: This exploratory observational study assessed 10 DBP and clinical scores at the start (T1) and end (T2) of a two-week PD-MCT of 25 PD in patients (mean age: 66.9 years, median HY stage: 2.5). Subjects performed four straight walking tasks under single- and dual-task conditions, and four balance tasks. RESULTS: At T1, reduced gait velocity and larger sway area correlated with motor severity. Shorter strides during motor-motor dual-tasking correlated with motor complications. From T1 to T2, gait velocity improved, especially under dual-task conditions, stride length increased for motor-motor dual-tasking, and clinical scores measuring motor severity, balance, dexterity, executive functions, and motor complications changed favorably. Other gait parameters did not change significantly. Changes in motor complications, motor severity, and fear of falling correlated with changes in stride length, sway area, and measures of gait stability, respectively. CONCLUSION: DBP of gait and balance reflect clinical scores, e.g., those of motor severity. PD-MCT significantly improves gait velocity and stride length and favorably affects additional DBP. Motor complications and fear of falling are factors that may influence the response to PD-MCT. A DBP-based assessment on admission to PD inpatient treatment could allow for more individualized therapy that can improve outcomes. TRIAL REGISTRATION NUMBER AND DATE: DRKS00020948 number, 30-Mar-2020, retrospectively registered.

Residents as teachers in Neurology: a Germany-wide survey on the involvement of neurological residents in clinical teaching.

BACKGROUND: Residents play an important role in the clinical training of medical students, spending up to 25% of their daily work teaching. In the US medical curriculum didactic courses for residents already exist and their role as a teacher is firmly anchored. In Germany, there are no fixed regulations or residents-as-teachers-programs. The aim of this study was to evaluate the activities of neurological residents in clinical teaching. METHODS: We conducted a prospective cross-sectional online survey among neurological residents in Germany. The evaluation was carried out descriptively and by means of text analysis. RESULTS: 138 residents from 39 German neurological university hospitals answered the survey. Nearly half of them needed the teaching activity as part of their career planning. The residents are mostly involved in practical courses. More than 80% stated, that they enjoy teaching. 64% stated that there were no preparatory courses for teaching at their hospital/university. 78.4% of the respondents received no or merely insufficient feedback for their own teaching and 62.5% had only little or even no knowledge about the university curriculum. CONCLUSIONS: By teaching medical students, residents play an outstanding role in recruiting students for neurology and, simultaneously, teaching leads an improvement in the residents' own learning. To encourage young neurologists as teachers and-at the same time as learners-Clinic directors and universities should promote residents-as-teachers programs in neurology and reward the residents' teaching activities.

SARS-CoV-2, COVID-19 and Parkinson's Disease-Many Issues Need to Be Clarified-A Critical Review.

Neurological manifestations during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are of interest, regarding acute treatment and the so-called post-COVID-19 syndrome. Parkinson's disease (PD) is one of the most common neurodegenerative movement disorders worldwide. Hence, the influence of SARS-CoV-2 and the COVID-19 syndrome on PD patients has raised many questions and produced various publications with conflicting results. We reviewed the literature, with respect to symptoms, treatment, and whether the virus itself might cause PD during the SARS-CoV-2 pandemic in SARS-CoV-2-affected symptomatic PD patients (COVID-19 syndrome). In addition, we comment on the consequences in non-symptomatic and non-affected PD patients, as well as post-COVID syndrome and its potential linkage to PD, presenting our own data from our out-patient clinic.

Blood-based biomarker in Parkinson's disease: potential for future applications in clinical research and practice.

The clinical presentation of Parkinson's disease (PD) is both complex and heterogeneous, and its precise classification often requires an intensive work-up. The differential diagnosis, assessment of disease progression, evaluation of therapeutic responses, or identification of PD subtypes frequently remains uncertain from a clinical point of view. Various tissue- and fluid-based biomarkers are currently being investigated to improve the description of PD. From a clinician's perspective, signatures from blood that are relatively easy to obtain would have great potential for use in clinical practice if they fulfill the necessary requirements as PD biomarker. In this review article, we summarize the knowledge on blood-based PD biomarkers and present both a researcher's and a clinician's perspective on recent developments and potential future applications.

Immediate-release/extended-release amantadine (OS320) to treat Parkinson's disease with levodopa-induced dyskinesia: Analysis of the randomized, controlled ALLAY-LID studies.

BACKGROUND: Immediate-release (IR) amantadine has been used for treatment of levodopa induced dyskinesia (LID). The immediate-release/extended-release (IR/ER) amantadine formulation OS320 (OSMOLEX ER®) contains an IR outer layer and ER core for once-daily dosing. OBJECTIVE: Report individual and pooled results for the similarly designed double-blind, placebo-controlled ALLAY-LID I and II trials, assessing IR/ER-amantadine for LID. METHODS: PD patients with LID were randomized to IR/ER-amantadine 193 mg, 258 mg, or placebo. Primary endpoint was Unified Dyskinesia Rating Scale (UDysRS) score change from baseline to Day 98. Secondary outcome was ON time without troublesome dyskinesia based on diaries. Exploratory outcomes were other diary states (including OFF), MDS-UPDRS Parts II + III and Fatigue Severity Scale. RESULTS: Overall, 222 individuals enrolled (N = 87 ALLAY-LID I, N = 135 ALLAY-LID II); both trials terminated early for sponsor's decision. While ALLAY-LID I did not meet its primary endpoint, a significant reduction in UDysRS scores versus placebo was observed in ALLAY-LID II for both 193 mg and 258 mg doses. In the pooled analysis, placebo-adjusted UDysRS score differences were -5.5 [-9.8, -1.2], p = 0.012 and -5.2 [-9.5, -0.9], p = 0.017, respectively. IR/ER-amantadine 258 mg significantly increased time spent ON without troublesome dyskinesia in ALLAY-LID II and pooled analysis. Reductions in ON time with dyskinesia supported the primary outcome. There was no effect on OFF time or other outcomes. Overall, 13.3% (193 mg), 18.7% (258 mg) and 11.1% (placebo) discontinued for adverse events, most commonly hallucinations (4.0%, 10.7%, and 1.4%, respectively). CONCLUSIONS: IR/ER-amantadine significantly reduced LID in ALLAY-LID II but not in ALLAY-LID I; post-hoc pooled data also indicated a positive treatment effect on LID.

Monogenetic Forms of Parkinson's Disease - Bridging the Gap Between Genetics and Biomarkers.

The therapy of neurodegenerative diseases such as Parkinson's disease (PD) is still limited to the treatment of symptoms and primarily aimed at compensating for dopaminergic hypofunction. Numerous disease-modifying therapies currently in the pipeline attempt to modify the underlying pathomechanisms. In recent decades, the results of molecular genetics and biomarker research have raised hopes of earlier diagnosis and new neuroprotective therapeutic approaches. As the disease-causing processes in monogenetic forms of PD are better understood than in sporadic PD, these disease subsets are likely to benefit first from disease-modifying therapies. Recent studies have suggested that disease-relevant changes found in genetically linked forms of PD (i.e., PARK-LRRK2, PARK-GBA) can also be reproduced in patients in whom no genetic cause can be found, i.e., those with sporadic PD. It can, therefore, be assumed that as soon as the first causal therapy for genetic forms of PD is approved, more patients with PD will undergo genetic testing and counseling. Regarding future neuroprotective trials in neurodegenerative diseases and objective parameters such as biomarkers with high sensitivity and specificity for the diagnosis and course of the disease are needed. These biomarkers will also serve to monitor treatment success in clinical trials. Promising examples in PD, such as alpha-synuclein species, lysosomal enzymes, markers of amyloid and tau pathology, and neurofilament light chain, are under investigation in blood and CSF. This paper provides an overview of the opportunities and current limitations of monogenetic diagnostic and biomarker research in PD and aims to build a bridge between current knowledge and association with PD genetics and biomarkers.

[Adenosine A2A Receptor Antagonists as a Treatment Option for Parkinson's Disease?] / Adenosin A2A Rezeptorantagonisten als Therapieoption beim idiopathischen Parkinson-Syndrom?

In Parkinson's disease, the focus has long been on motor symptoms and therapy with dopaminergic substances. In recent years, the importance of non-motor symptoms has been increasingly recognized, as they occur early in the course of the disease and restrict considerably the quality of life. However, this also made the need for treatment of non-dopaminergic deficits obvious. Adenosine A2A receptor antagonists were identified as an additional therapy, since the adenosine A2A receptors are non-dopaminergic and selectively localized in the basal ganglia. This means that the striato-thalamo-cortical loops can be modulated. An adenosine A2A receptor antagonist was already approved in Japan in 2013 and in the USA in 2019 as an add-on to L-DOPA. Approval for this drug in Europe is expected in the near future. In this overview, we present the theoretical basis and current data on its efficacy and therapeutic use.

Update on CSF Biomarkers in Parkinson's Disease.

Progress in developing disease-modifying therapies in Parkinson's disease (PD) can only be achieved through reliable objective markers that help to identify subjects at risk. This includes an early and accurate diagnosis as well as continuous monitoring of disease progression and therapy response. Although PD diagnosis still relies mainly on clinical features, encouragingly, advances in biomarker discovery have been made. The cerebrospinal fluid (CSF) is a biofluid of particular interest to study biomarkers since it is closest to the brain structures and therefore could serve as an ideal source to reflect ongoing pathologic processes. According to the key pathophysiological mechanisms, the CSF status of α-synuclein species, markers of amyloid and tau pathology, neurofilament light chain, lysosomal enzymes and markers of neuroinflammation provide promising preliminary results as candidate biomarkers. Untargeted approaches in the field of metabolomics provide insights into novel and interconnected biological pathways. Markers based on genetic forms of PD can contribute to identifying subgroups suitable for gene-targeted treatment strategies that might also be transferable to sporadic PD. Further validation analyses in large PD cohort studies will identify the CSF biomarker or biomarker combinations with the best value for clinical and research purposes.