Classification of advanced stages of Parkinson's disease: translation into stratified treatments.

Advanced stages of Parkinson's disease (advPD) still impose a challenge in terms of classification and related stage-adapted treatment recommendations. Previous concepts that define advPD by certain milestones of motor disability apparently fall short in addressing the increasingly recognized complexity of motor and non-motor symptoms and do not allow to account for the clinical heterogeneity that require more personalized approaches. Therefore, deep phenotyping approaches are required to characterize the broad-scaled, continuous and multidimensional spectrum of disease-related motor and non-motor symptoms and their progression under real-life conditions. This will also facilitate the reasoning for clinical care and therapeutic decisions, as neurologists currently have to refer to clinical trials that provide guidance on a group level; however, this does not always account for the individual needs of patients. Here, we provide an overview on different classifications for advPD that translate into critical phenotypic patterns requiring the differential therapeutic adjustments. New concepts refer to precision medicine approaches also in PD and first studies on genetic stratification for therapeutic outcomes provide a potential for more objective treatment recommendations. We define novel treatment targets that align with this concept and make use of emerging device-based assessments of real-life information on PD symptoms. As these approaches require empowerment of patients and integration into treatment decisions, we present communication strategies and decision support based on new technologies to adjust treatment of advPD according to patient demands and safety.

[Epidemiology of Parkinson's Disease and Current Concepts of Outpatient Care in Germany]. / Epidemiologie der Parkinsonerkrankung und aktuelle ambulante Versorgungskonzepte in Deutschland.

The ambulatory care of patients with Parkinson's disease (PD) in Germany has been established for a long time. As the prevalence of Parkinson's disease continues to increase, the outpatient neurological sector is becoming more and more important and needs to adapt itself to current needs. This includes an optimization of the care structures for Parkinson's patients as well as adequate concepts for the execution of differentiated diagnostics and therapy. For many patients care is provided by non-specialized neurological practices or general practitioners, without exchange of views with neurologists or a specialized university outpatient clinic for movement disorders. A connective link between these care structures could be provided by a "practice with focus on Parkinson's disease", whose idea and conception is presented in this article. In addition to the necessity and usefulness of such an institution, structural prerequisites and basic principles for the treatment of Parkinsonian patients in a disease state-centered manner will be presented but also current limitations of the concept are pointed out. This article presents the results of an expert workshop on Parkinson's disease, which took place in Frankfurt am Main on 21 November 2015.

Advanced stages of PD: interventional therapies and related patient-centered care.

During the last decades, symptomatic treatment of motor symptoms of Parkinson's disease (PD) improved continuously and is reflected by long-range independency of the patient during the disease course. However, advanced stages of PD still represent an important challenge to patients, caregivers and treating physicians. In patients with advanced PD, interventional therapy strategies are increasingly applied. These device-related treatment strategies using pump-based continuous dopaminergic stimulation (CDS) or deep brain stimulation (DBS) opened new treatment options especially if motor complications predominate. Well-designed clinical studies on these interventional therapeutic approaches provided class 1 evidence for the efficacy of DBS and CDS in advanced PD and opened new perspectives for their use in earlier disease stages also. Therefore, careful selection of patients amenable to the (semi)invasive therapy options becomes more and more important and requires an interdisciplinary setting that accounts for (i) optimal patient information and awareness, (ii) selection of best individual treatment modality, (iii) training of relatives and caregivers, (iv) management of complications, and (v) follow-up care. Here, we address these topics by summarizing current state-of-the-art in patient selection, providing specificities of treatment options and troubleshooting, and defining steps towards an optimized patient-centered care. Interventional therapies pioneer in the area of individualized treatment approaches for PD, and may be complemented in the future by biomarker-based improved stratification and by closed-loop systems for adaptive therapeutic strategies. In the present review, we summarize the proceedings of an Expert Workshop on Parkinson's disease held on November 22, 2014 in Frankfurt, Germany.

Intrathecal application of autologous bone marrow cell preparations in Parkinsonian syndromes.

BACKGROUND: A growing number of patients is treated with intrathecal application of autologous bone marrow cells (aBMCs), but clinical data are completely lacking in movement disorders. We provide first clinical data on efficacy and safety of this highly experimental treatment approach in parkinsonian syndromes. METHODS: Retrospective data collection from patients with parkinsonism who spontaneously sought cell treatment. The application procedure was neither recommended nor performed by the authors. RESULTS: We report 17 patients with parkinsonian syndromes (Parkinson's disease [PD], n = 7; multiple system atrophy [MSA], n = 7; various, n = 3) who received intrathecal application of aBMCs. We did not observe any changes in motor function, activities of daily living, global clinical impression, or antiparkinsonian medication after a median observation period of 10 months. Two patients reported a worsening of parkinsonian symptoms, but the intervention was otherwise safe and well-tolerated. CONCLUSIONS: Intrathecal application of aBMCs in uncontrolled conditions produces no clinical benefit in parkinsonian syndromes.

Specialized Staff for the Care of People with Parkinson's Disease in Germany: An Overview.

Access to specialized care is essential for people with Parkinson´s disease (PD). Given the growing number of people with PD and the lack of general practitioners and neurologists, particularly in rural areas in Germany, specialized PD staff (PDS), such as PD nurse specialists and Parkinson Assistants (PASS), will play an increasingly important role in the care of people with PD over the coming years. PDS have several tasks, such as having a role as an educator or adviser for other health professionals or an advocate for people with PD to represent and justify their needs. PD nurse specialists have been established for a long time in the Netherlands, England, the USA, and Scandinavia. In contrast, in Germany, distinct PDS models and projects have been established. However, these projects and models show substantial heterogeneity in terms of access requirements, education, theoretical and practical skills, principal workplace (inpatient vs. outpatient), and reimbursement. This review provides an overview of the existing forms and regional models for PDS in Germany. PDS reimbursement concepts must be established that will foster an implementation throughout Germany. Additionally, development of professional roles in nursing and more specialized care in Germany is needed.

Recommendations for Standards of Network Care for Patients with Parkinson's Disease in Germany.

Although our understanding of Parkinson´s disease (PD) has improved and effective treatments are available, caring for people with PD remains a challenge. The large heterogeneity in terms of motor symptoms, nonmotor symptoms, and disease progression makes tailored individual therapy and individual timing of treatment necessary. On the other hand, only limited resources are available for a growing number of patients, and the high quality of treatment cannot be guaranteed across the board. At this point, networks can help to make better use of resources and improve care. The working group PD Networks and Integrated Care, part of the German Parkinson Society, is entrusted to convene clinicians, therapists, nurses, researchers, and patients to promote the development of PD networks. This article summarizes the work carried out by the working group PD Networks and Integrated Care in the development of standards of network care for patients with PD in Germany.

Do We Need to Rethink the Epidemiology and Healthcare Utilization of Parkinson's Disease in Germany?

Epidemiological aspects of Parkinson's disease (PD), co-occurring diseases and medical healthcare utilization of PD patients are still largely elusive. Based on claims data of 3.7 million statutory insurance members in Germany in 2015 the prevalence and incidence of PD was determined. PD cases had at least one main hospital discharge diagnosis of PD, or one physician diagnosis confirmed by a subsequent or independent diagnosis or by PD medication in 2015. Prevalence of (co-)occurring diseases, mortality, and healthcare measures in PD cases and matched controls were compared. In 2015, 21,714 prevalent PD cases (standardized prevalence: 511.4/100,000 persons) and 3,541 incident PD cases (standardized incidence: 84.1/100,000 persons) were identified. Prevalence of several (co-)occurring diseases/complications, e.g., dementia (PD/controls: 39/13%), depression (45/22%), bladder dysfunction (46/22%), and diabetes (35/31%), as well as mortality (10.7/5.8%) differed between PD cases and controls. The annual healthcare utilization was increased in PD cases compared to controls, e.g., regarding mean ± SD physician contacts (15.2 ± 7.6/12.2 ± 7.3), hospitalizations (1.3 ± 1.8/0.7 ± 1.4), drug prescriptions (overall: 37.7 ± 24.2/21.7 ± 19.6; anti-PD medication: 7.4 ± 7.4/0.1 ± 0.7), assistive/therapeutic devices (47/30%), and therapeutic remedies (57/16%). The standardized prevalence and incidence of PD in Germany as well as mortality in PD may be substantially higher than reported previously. While frequently diagnosed with co-occurring diseases/complications, such as dementia, depression, bladder dysfunction and diabetes, the degree of healthcare utilization shows large variability between PD patients. These findings encourage a rethinking of the epidemiology and healthcare utilization in PD, at least in Germany. Longitudinal studies of insurance claims data should further investigate the individual and epidemiological progression and healthcare demands in PD.

Tolcapone improves sleep in patients with advanced Parkinson's disease (PD).

Efficacy of the long-acting catechol-O-methyltransferase (COMT)-inhibitor, tolcapone on sleep quality was studied in 61 patients with advanced PD in a prospective open-label multicenter non-interventional trial. Main outcome measures were the PD sleep scale (PDSS). Further outcome measures were global clinical impression of change (GCI-C), daily off-time, activities of daily living (UPDRS part II), quality of life (EuroQoL-5D), Epworth sleepiness scale (ESS) and adverse events reports. All efficiency and safety parameters were assessed 4 weeks after the switch to tolcapone and compared to baseline. The mean±S.D. daily dose of tolcapone was 294.2±36.9 mg/day at the final assessment. The mean PDSS scores significantly improved from 21.6±8.1 at baseline to 16.3±7.7 at final assessment (p<0.0001). Consistently, daytime sleepiness was significantly reduced as reflected by lower scores on the ESS (p=0.0057). Further efficacy parameters including GCI-C, daily off-time, activities of daily living, and quality of life were also significantly improved. Tolcapone was in general well tolerated and safe. This observational study provides first evidence that tolcapone improves sleep quality and reduces daytime sleepiness in patients suffering from advanced PD.