Subcutaneous foslevodopa/foscarbidopa (LDp/CDp) infusion is approved for treating motor fluctuations and dyskinesias in patients with advanced Parkinson’s disease (aPD). However, efficacy data on non-motor symptoms (NMS) are limited. To evaluate the effects of LDp/CDp treatment on NMS in patients with aPD. Retrospective analysis of efficacy of LDp/CDp on NMS after 3 week therapy in a Parkinson’s day-clinic setting and further 6 weeks of outpatient treatment. Twenty-one patients with aPD were assessed at baseline (T0), after 3 weeks (T1), and after 9 weeks (T2). Assessments included broader NMS according to MDS-UPDRS Part I and NMS questionnaire (NMSQ) and in more detail sleep (PDSS-2) and depression (BDI-2). Mean MDS-UPDRS I total score significantly improved by 27

IntroductionApproximately 20% of people with Parkinson’s disease (PwP) in Germany need professional long-term care (LTC). Previous data have indicated a rather poor LTC situation and the need for more profound analyses. Therefore, we aimed to assess the quantity and quality of LTC care for PwP and the knowledge on Parkinson’s disease (PD) in German LTC nursing staff.MethodsData from our nationwide, cross-sectoral Care4PD survey, which was distributed postally and online, were analyzed. Out of 295 completed anonymous LTC nurse questionnaires, 288 were included, with descriptive results presented in this study.ResultsIn terms of age and work experience, a representative sample of 288 participants, the majority (79%) of whom were registered LTC nurses, participated in the study. A total of 95% of them had certain experience with people with Parkinson’s disease (PwP). On average, each nurse supported approximately three PwP per week, with a mean care time of 48 min per day. A total of 17% of participants complained about “never” having enough staff, and 50% complained about “frequently changing” LTC personnel in their institution. Additionally, 10% reported “unsafe” care quality, with the occurrence of avoidable complications. Insufficient knowledge on PD and the importance of PD-specialized training were highlighted, with current training options often not recognized. Optimization suggestions consisted of more personnel and time capacities, educational measures, and interprofessional exchange.Discussion/conclusionImproving PwP care in German LTC facilities requires not only the general provision of more personnel and time resources but also, in particular, the development of greater expertise among LTC nursing staff to optimize care quality. The existing, but little-known, training opportunities should therefore be made known to a larger number of LTC nurses.

Patients with advanced Parkinson's disease (PD) often need to continue with device-aided therapies (DAT), such as intestinal and subcutaneous infusion therapies. Recently, continuous subcutaneous administration of foslevodopa/foscarbidopa (LDp/CDp) has emerged as a new therapeutic method. Two years after its approval in Germany, a large amount of real-world experience has been collected. Based on this, we present important practical recommendations to help clinicians optimise treatment. Key topics include identifying suitable patients, approaches to initiation and dose determination as well as strategies for balancing LDp/CDp with concomitant oral dopaminergic therapies. Practical challenges, particularly infusion site reactions and neuropsychiatric vulnerability in older or cognitively impaired patients, are discussed, and recommendations are presented on how to prevent and manage these adverse effects during routine management. The review also addresses reasons for discontinuation, organisational factors relevant to real-world implementation and future directions in pump technology. Overall, LDp/CDp is effective in managing motor fluctuations and provides sustained benefits with an overall favourable tolerability profile. Dermatological reactions are common but manageable, and careful adjustment of oral medication rather than rapid pursuit of monotherapy is advisable. The rate of early discontinuation has decreased with growing clinical experience.

Gastrointestinal Disorders in people with Parkinson's disease (PwP) are able to cause widespread clinical symptoms which can be challenging to classify in day-to-day clinical practice. In the upper gastrointestinal tract (GIT) oropharyngeal dysphagia, esophageal motility disorders as well as delayed gastric emptying may cause nutrition problems and reduce the efficacy of oral pharmacotherapy. In the lower GIT, bacterial overgrowth and prolonged colorectal transit times induce different stages of constipation leading to reduced quality of life and GIT comorbidities as well. Most of these symptoms reflect alpha-synuclein pathology in both the enteric nervous system and at various sites of the peripheral and central nervous systems. Besides, the growing use of various device aided therapies may additionally raise specific clinical questions about the interference with the GIT motility. This standard operating procedure (SOP) is intended to provide specific recommendations for diagnostic steps as well as therapeutic options, especially for interprofessional neurological outpatient care teams.

Background: Progressive supranuclear palsy (PSP) is a tauopathy marked by early degeneration of brainstem nuclei such as the locus coeruleus (LC), a central player of the ascending reticular activating system (ARAS). ARAS dysfunction contributes to cognitive and arousal disturbances and is increasingly recognized as a therapeutic target. Methods: 14 PSP patients (eight females, age 70.81 ± 6.32 years, disease duration 4.69 ± 3.24 years) were assessed before and after ≥4 weeks of SNRI (serotonin-norepinephrine reuptake inhibitor) treatment. Participants were assessed by non-invasive neurophysiological measures as pupillometry, performed at rest and during an auditory oddball paradigm, and clinically, using PSP-specific clinical scales and quantitative gait analysis. Pupil, cognitive, and gait parameters were compared with age-matched healthy controls. Results: At baseline, pupil size, pupil dilation responses and surprise pupil responses were reduced in PSP patients compared to controls, accompanied by impaired executive functions, reduced phonemic verbal fluency and depressive symptoms in PSP patients. SNRI treatment selectively rescued certain impaired pupil metrics in PSP, leading to a significant improvement of the surprise pupil response and partial normalization of pupil fluctuations at rest. Pupil metric changes were associated with notable improvement in executive functions and quality of life at follow-up. Conclusion: In summary, our findings reveal altered pupil-linked arousal regulation in PSP and its modulation by SNRI therapy, suggesting pupillometric indices as promising biomarkers of therapeutic response. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial DRKS00025481 ### Funding Statement This study was funded by the DFG (German Research Foundation), SFB 936, project C8 (M. Pötter-Nerger, C. Moll) and project A7 (T. Donner). M. Maheu is supported by a postdoctoral fellowship from the Humboldt Stiftung and by the Fondation Bettencourt Schueller. ### 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 of the Medical Association Hamburg, Germany gave ethical approval for this work. 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 The datasets generated for this study are available upon reasonable request to the corresponding author.

BackgroundSubcutaneous foslevodopa/foscarbidopa (LDp/CDp) has expanded the treatment options in advanced Parkinson’s disease (aPD). However, the most appropriate therapeutic setting for therapy implementation is not clear.ObjectiveTo present a concept for LDp/CDp therapy implementation in a Parkinson’s day-clinic and efficacy and safety outcome data from patients under the new therapeutic regimen.MethodsRetrospective clinical data were collected from the first 24 patients with aPD who were initiated on LDp/CDp treatment at the Hamburg Parkinson’s day-clinic. Outcome parameters were analyzed in terms of motor symptoms (MDS -UPDRS II-IV), safety aspects and effects on patients’ quality of life (PDQ-39).ResultsThe concept of the Parkinson’s Day-clinic enabled the successful implementation of LDp/CDp therapy in patients with advanced Parkinson’s disease (aPD). It provided individualized medical supported via neurologists, specialized nurses and therapists and thus facilitated the transition from clinic-based care to home-based support. Compared to previous optimized oral treatment, the application of LDp/CDp significantly reduced motor complications such as dyskinesias and motor fluctuations by 53% on the MDS-UPDRS IV (p = 0.0094). Motor function improvements were paralleled by a numerical increase in activities of daily living scores (MDS-UPDRS II) and improvement in long-term mobility (PDQ-39 mobility subscale), suggesting potential benefits in daily functioning and perceived mobility.ConclusionThe value of our data is limited by its retrospective design and small sample size. However, the data suggest that a proper day-clinic setting enables the successful implementation of subcutaneous LDp/CDp therapy with improvement of motor functions and reduction of side effects. It also ensures the necessary intensive medical support and offers comprehensive device-related and psychosocial guidance for both patients and caregivers.

Background Progressive supranuclear palsy (PSP) is a rare neurodegenerative movement disorder clinically characterized by falls, axial rigidity, vertical supranuclear gaze palsy, bradykinesia, and cognitive decline. There is a relative lack of studies on the functional neuroimaging correlates of cognitive impairment in PSP. Objective This study investigated the relationship between regional cerebral glucose metabolism as assessed by static 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) with global scaling and the profile of cognitive performance according to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test battery in a sample of PSP patients representative of clinical practice. Methods 22 PSP patients from three tertiary movement disorder centers with CERAD testing and FDG-PET in close proximity were included retrospectively. Neuropsychological test performance was assessed for correlation with FDG uptake on a voxel-by-voxel basis with cluster-level correction for multiple testing, separately for each subtest. Results In comparison to matched healthy controls, PSP patients showed reduced FDG uptake in the left inferior frontal gyrus and right angular gyrus. Reduced overall cognitive performance according to Montreal Cognitive Assessment was associated with reduced FDG uptake in the right frontal eye field. Word list learning correlated with FDG uptake in the left frontal eye field, while language fluency was linked to FDG uptake in the bilateral premotor and supplementary motor areas. Conclusions Reduction of FDG uptake in PSP primarily affects frontal brain regions and is linked to the performance in specific cognitive domains. These findings may have implications for the interpretation of FDG-PET to support the etiological diagnosis of PSP.

Non-motor symptoms frequently develop throughout the disease course of Parkinson’s disease (PD), and pose affected individuals at risk of complications, more rapid disease progression and poorer quality of life. Addressing such symptom burden, the 2023 revised “Parkinson’s disease” guideline of the German Society of Neurology aimed at providing evidence-based recommendations for managing PD non-motor symptoms, including autonomic failure, pain and sleep disturbances. Key PICO (Patient, Intervention, Comparison, Outcome) questions were formulated by the steering committee and refined by the assigned authors. Recommendations were drafted based on relevant studies, systematic reviews, meta-analyses and high-quality guidelines identified by the literature search. They were subsequently reviewed, revised, and voted by the Guideline Group in online consensus conferences. Consensus was achieved in case of > 75

BACKGROUND:Diagnostic criteria for progressive supranuclear palsy (PSP) include midbrain atrophy in MRI and hypometabolism in [18F]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.

Die Einschätzung der Fahrtauglichkeit bei Patienten mit Parkinson-Erkrankung ist im Praxisalltag wichtig, aber schwierig und wird oft sowohl von Patienten als auch Ärzten ungern thematisiert. Dieser Beitrag zeigt, welche medizinischen Aspekte eine verminderte Fahrkompetenz entweder als fehlende generelle Fahrtauglichkeit oder als temporär eingeschränkte Fahrfähigkeit anzeigen, welche juristischen Aspekte der Arzt berücksichtigen muss und schlägt ein praxisnahes Vorgehen zur Abklärung der Fahrkompetenz vor.

Background and objectiveCognitive impairment and dementia as well as affective disorders are common and debilitating syndromes that develop in people with Parkinson's disease (PwPD). The authors summarized recommendations for the 2023 updated German guidelines on "Parkinson's disease" from the German Neurological Society (DGN), focusing on the diagnosis and treatment of these disorders.MethodsThe recommendations were based on literature reviews, other relevant guidelines, and expert opinions.ResultsMeasurements to assess cognitive and affective states were reviewed for psychometric properties, use in routine clinical practice, and availability in German. To improve mild cognitive impairment, cognitive training and physical aerobic training are recommended. To treat Parkinson's disease (PD)-related dementia, cognitive stimulation (as a non-pharmacological intervention) and acetylcholinesterase inhibitors (AChEIs, i.e., rivastigmine) are recommended. Cognitive behavioral therapy is recommended to treat depression, anxiety, and fear of progression. Physical interventions are recommended to treat depression, fatigue, and apathy. Optimized dopaminergic treatment is the first-line pharmacological strategy recommended to manage depression, apathy, anhedonia, fatigue, and mood swings. Major depression can be additionally treated using venlafaxine or desipramine, while moderate depression can be treated pharmacologically according to its clinical phenotype (psychomotor retardation or agitation) and comorbidities (e.g., sleep disturbances, pain). Venlafaxine and nortriptyline can be used to treat anhedonia, while citalopram can be used for anxiety.ConclusionsIn addition to the updated pharmacological treatment options, new insights into recommendations for standardized diagnostics and non-pharmacological interventions were provided for the German health care system. However, more studies are needed to explore the full potential of non-pharmacological interventions to treat and prevent cognitive impairment and affective disorders.

Parkinson's disease (PD) is characterized by the disruption of repetitive, concurrent and sequential motor actions due to compromised timing-functions principally located in cortex-basal ganglia (BG) circuits. Increasing evidence suggests that motor impairments in untreated PD patients are linked to an excessive synchronization of cortex-BG activity at beta frequencies (13-30 Hz). Levodopa and subthalamic nucleus deep brain stimulation (STN-DBS) suppress pathological beta-band reverberation and improve the motor symptoms in PD. Yet a dynamic tuning of beta oscillations in BG-cortical loops is fundamental for movement-timing and synchronization, and the impact of PD therapies on sensorimotor functions relying on neural transmission in the beta frequency- range remains controversial. Here, we set out to determine the differential effects of network neuromodulation through dopaminergic medication (ON and OFF levodopa) and STN-DBS (ON-DBS, OFF-DBS) on tapping synchronization and accompanying cortical activities. To this end, we conducted a rhythmic finger-tapping study with high-density EEG-recordings in 12 PD patients before and after surgery for STN-DBS and in 12 healthy controls. STN-DBS significantly ameliorated tapping parameters as frequency, amplitude and synchrony to the given auditory rhythms. Aberrant neurophysiologic signatures of sensorimotor feedback in the beta-range were found in PD patients: their neural modulation was weaker, temporally sluggish and less distributed over the right cortex in comparison to controls. Levodopa and STN-DBS boosted the dynamics of beta-band modulation over the right hemisphere, hinting to an improved timing of movements relying on tactile feedback. The strength of the post-event beta rebound over the supplementary motor area correlated significantly with the tapping asynchrony in patients, thus indexing the sensorimotor match between the external auditory pacing signals and the performed taps. PD patients showed an excessive interhemispheric coherence in the beta-frequency range during the finger-tapping task, while under DBS-ON the cortico-cortical connectivity in the beta-band was normalized. Ultimately, therapeutic DBS significantly ameliorated the auditory-motor coupling of PD patients, enhancing the electrophysiological processing of sensorimotor feedback-information related to beta-band activity, and thus allowing a more precise cued-tapping performance.

The use of medical Cannabis has increased in recent years due to changing legal circumstances in many countries. Approval exists only for a few neurological conditions such as rare forms of epilepsy or spasticity in multiple sclerosis. Beyond that, however, medical Cannabis is used for a wide range of neurological conditions and symptoms. In Germany, in parallel with new legislation that has simplified the prescription of medical Cannabis , an accompanying survey has been implemented for which initial data are now available. In this context, our review provides an overview of the evidence for the therapeutic use of medical Cannabis in neurology, the potential benefits, and side effects.

Background and objectivesResearch on driving ability in people with multiple sclerosis (MS) suggests that they might be at risk for unsafe driving due to MS-related motor, visual, and cognitive impairment. Our first aim was to investigate differences in driving ability and performance between people with MS (PwMS) and those without any neurologic or psychiatric disease (“controls”). Secondly, we determined disease-related factors influencing driving ability in PwMS.MethodsWe prospectively compared standardized performance in a driving simulator between 97 persons with early MS [mean (SD) = 6.4 (7.3) years since diagnosis, mean (SD) Expanded Disability Status Scale (EDSS) = 2.5 (1.4)] and 94 group-matched controls. Participants completed an extensive examination comprising questionnaires and assessments regarding driving, cognitive and psychological factors, as well as demographic and disease-related measures. Between-group comparisons of driving-relevant neuropsychological tests and driving performance were done. Correlations were performed to define demographic and disease-related factors on driving performance in MS.ResultsIn a driving simulator setting, PwMS had more driving accidents [T(188) = 2.762, p = 0.006], reacted slower to hazardous events [T(188) = 2.561, p = 0.011], made more driving errors [T(188) = 2.883, p = 0.004] and had a worse Driving Safety Score (DSS) [T(188) = 3.058, p = 0.003] than controls. The only disease-related measure to be associated with most driving outcomes was the Wechsler Block-Tapping test (WMS-R) backward: number of accidents (r = 0.28, p = 0.01), number of driving errors (r = 0.23, p = 0.05) and DSS (r = −0.23, p = 0.05).ConclusionDriving performance in a simulator seems to be reduced in PwMS at an early stage of disease compared to controls, as a result of increased erroneous driving, reduced reaction time and higher accident rate. MS-related impairment in mobility, vision, cognition, and in psychological and demographic aspects showed no or only minimal association to driving ability, but impairment in different areas of cognition such as spatial short-term memory, working memory and selective attention correlated with the number of accidents, and might indicate a higher risk for driving errors and worse performance. These results show that driving ability is a complex skill with involvement of many different domains, which need further research.

Deep brain stimulation can influence the speech and voice quality in Parkinson´s disease (PD). This controlled, randomized, double-blind, cross-over clinical trial was conducted in 15 PD patients with bilateral subthalamic deep brain stimulation (DBS) to compare the effects of STN-DBS with combined subthalamic and nigral stimulation (STN + SNr-DBS) and DBS OFF on speech and voice parameters in PD patients. Speech and voice were analyzed subjectively using questionnaires (voice/pronunciation quality VAS, VHI, SHI) and objectively using audio analysis (maximum phonation time, AVQI, mean F0, intonation, syllable rate, reading time). Both stimulation conditions, STN + SNr-DBS and STN-DBS, revealed heterogeneous effects on speech and voice production with a slight beneficial effect on the voice quality of individual patients compared to DBS OFF, but not in the whole group. Small, but not significant effects were seen only in subjective voice quality on the VAS and intonation (both stimulation conditions compared to DBS OFF). No significant changes of the objective speech parameters during the audio analysis could be observed (both stimulation conditions compared to DBS OFF). There were no significant differences between STN + SNr-DBS and STN-DBS in any speech and voice domain. The beneficial effects on speech and voice production are minor in most patients compared to the motor improvements by DBS. Both STN-DBS and STN + SNr-DBS were safe, with comparable effects between both DBS modes, and represent no contraindications from the perspective of the voice specialist.

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.

Tremor, whether arising from neurological diseases, other conditions, or medication side effects, significantly impacts patients' lives. Treatment complexities necessitate clear algorithms and strategies. Levodopa remains pivotal for Parkinson's tremor, though response variability exists. Some dopamine agonists offer notable tremor reduction targeting D2 receptors. Propranolol effectively manages essential tremor and essential tremor plus (ET/ET +), sometimes with primidone for added benefits, albeit dose-dependent side effects. As reserve medications anticholinergics and clozapine are used for treatment of parkinsonian tremor, 1-Octanol and certain anticonvulsant drugs for tremor of other orign, especially ET. Therapies such as invasive deep brain stimulation and lesional focused ultrasound serve for resistant cases. A medication review is crucial for all forms of tremor, but it is particularly important if medication may have triggered the tremor. Sensor-based detection and non-drug interventions like wristbands and physical therapy broaden diagnostic and therapeutic horizons, promising future tremor care enhancements. Understanding treatment nuances is a key for tailored tremor management respecting patient needs and tolerability. Successful strategies integrate pharmacological, non-invasive, and technological modalities, aiming for optimal symptom control and improved quality of life.