Kai F. Loewenbrück

The regulation of adult neural stem or progenitor cell (aNSC) proliferation and differentiation as an interplay of cell-intrinsic and local environmental cues remains in part unclear, impeding their role in putative regenerative therapies. aNSCs with all major properties of NSCs in vitro have been identified in a variety of brain regions beyond the classic neurogenic niches, including the caudal periventricular regions (PVRs) of the midbrain, though active neurogenesis is either limited or merely absent in these regions. To elucidate cell-intrinsic properties of aNSCs from various PVRs, we here examined the proliferation and early differentiation capacity of murine aNSCs from non-neurogenic midbrain PVRs (PVR_MB) compared to aNSCs from the neurogenic ventricular-subventricular zone (PVR_V-SVZ) 7 days after transplantation into the permissive pro-neurogenic niche of the dentate gyrus (DG) of the hippocampus in mice. An initial in vitro characterization of the transplants displayed very similar characteristics of both aNSC grafts after in vitro expansion with equal capacities of terminal differentiation into astrocytes and Tuj1⁺ neurons. Upon the allogenic transplantation of the respective aNSCs into the DG, PVR_MB grafts showed a significantly lower graft survival and proliferative capacity compared to PVR_V-SVZ transplants, whereby the latter are exclusively capable of generating new neurons. Although these differences might be—in part—related to the transplantation procedure and the short-term study design, our data strongly imply important cell-intrinsic differences between aNSCs from neurogenic compared to non-neurogenic PVRs with respect to their neurogenic potential and/or their sensitivity to neurogenic cues.

Objective: To investigate diagnostic accuracy of a nerve ultrasound (US) protocol that is individualized to a patient’s clinical deficits for the differentiation of amyotrophic lateral sclerosis with predominant lower motoneuron disease (ALS/LMND) and multifocal motor neuropathy (MMN). Methods: Single-center, prospective, examiner-blinded, diagnostic study in two cohorts. Cohort I (model development): Convenience sample of subjects with ALS/LMND or MMN according to revised El-Escorial or EFNS guidelines. Cohort II (model validation): Consecutively recruited treatment-naïve subjects with suspected diagnosis of ALS/LMND or MMN. Cutoffs for 28 different US values were determined by Receiver Operating Curve (ROC) in cohort I. Area Under The Curve (AUC) of US was compared to nerve conduction studies (NCS). Diagnostic accuracy of US protocols, individualized according to clinical deficits, was compared to former rigid non-individualized protocols and to random examination site selection in cohort II. Results: 48 patients were recruited. In cohort I (28 patients), US had higher ROC AUCs than NCS, US 0.82 (0.12) (mean (standard deviation)), NCS (compound muscle action potential (CMAP) 0.60 (0.09), p < .001; two-sided t-test). US models based on the nerve innervating the clinically most affected muscles had higher correct classification rates (CCRs, 93%) in cohort II than former rigid protocols (85% and 80%), or models with random measurement site selection (66% and 80%). Conclusions: Clinically guided US protocols for differentiation of ALS/LMND from MMN increase diagnostic accuracy when compared to clinically unguided protocols. They also require less measurements sites to achieve this accuracy.

As integrated care is recognized as crucial to meet the challenges of chronic conditions such as Parkinson’s disease (PD), integrated care networks have emerged internationally and throughout Germany. One of these networks is the Parkinson Network Eastern Saxony (PANOS). PANOS aims to deliver timely and equal care to PD patients with a collaborative intersectoral structured care pathway. Additional components encompass personalized case management, an electronic health record, and communicative and educative measures. To reach an intersectoral consensus of the future collaboration in PANOS, a structured consensus process was conducted in three sequential workshops. Community-based physicians, PD specialists, therapists, scientists and representatives of regulatory authorities and statutory health insurances were asked to rate core pathway-elements and supporting technological, personal and communicative measures. For the majority of core elements/planned measures, a consensus was reached, defined as an agreement by >75% of participants. Additionally, six representatives from all partners involved in the network-design independently assessed PANOS based on the Development Model for Integrated Care (DMIC), a validated model addressing the comprehensiveness and maturity of integrated care concepts. The results show that PANOS is currently in an early maturation state but has the potential to comprehensively represent the DMIC if all planned activities are implemented successfully. Despite the favorable high level of consensus regarding the PANOS concept and despite its potential to become a balanced integrated care concept according to the DMIC, its full implementation remains a considerable challenge.

Integrated care is regarded as a key for care delivery to persons with chronic long-term conditions such as Parkinson’s disease. For persons with Parkinson’s disease, obtaining self-management support is a top priority in the context of integrated care. Self-management is regarded as a crucial competence in chronic diseases since the affected persons and their caregivers inevitably take up the main responsibility when it comes to day-to-day management. Formal self-management education programs with the focus on behavioral skills relevant to the induction and maintenance of behavioral change have been implemented as a standard in many chronic long-term conditions. However, besides the example of the Swedish National Parkinson School, the offers for persons with Parkinson’s disease remain fragmented and limited in availability. Today, no such program is implemented as a nationwide standard in Germany. This paper provides (1) a systematic review on structured self-management education programs specifically designed or adopted for persons with Parkinson’s disease, (2) presents the Swedish National Parkinson School as an example for a successfully implemented nationwide program and (3) presents a concept for the design, evaluation and long-term implementation of a future-orientated self-management education program for persons with Parkinson’s disease in Germany.

Parkinson’s disease is a complex neurodegenerative disease that can be best treated with a multi-disciplinary care approach. Building care networks has been shown as a useful tool to facilitate the integration of care services and improve outcomes for patients and care providers. However, experiences and practices relating to building a network are very limited in the field of Parkinson’s disease. This paper portrays existing Parkinson networks in Germany. With the help of a standardized template, description of networks and their building-blocks, so-called modules, were collected from all over Germany. Modules were rated in terms of their expected benefit and the required effort when implementing them, with the help of an expert survey. The rating showed that some modules were perceived as more important than others, but all modules were recognized as beneficial for patients and care providers. Overall, the German experience shows that building a Parkinson network facilitates the integration of care and provides a benefit to all stakeholders involved.

The objective of the study was to investigate nerve ultrasound (US) in comparison to nerve conduction studies (NCS) for differential diagnosis of amyotrophic lateral sclerosis with predominant lower motoneuron disease (ALS/LMND) and multifocal motor neuropathy (MMN). A single-center, prospective, examiner-blinded cross-sectional diagnostic study in two cohorts was carried out. Cohort I: convenience sample of subjects diagnosed with ALS/LMND or MMN (minimal diagnostic criteria: possible ALS (revised EL-Escorial criteria), possible MMN (European Federation of Neurosciences guidelines). Cohort II: consecutive subjects with suspected diagnosis of either ALS/LMND or MMN. Diagnostic US and NCS models were developed based on ROC analysis of 28 different US and 32 different NCS values measured in cohort I. Main outcome criterion was sensitivity/specificity of these models between ALS/LMND and MMN in cohort II. Cohort I consisted of 16 patients with ALS/LMND and 8 patients with MMN. For cohort II, 30 patients were recruited, 8 with ALS/LMND, 5 with MMN, and 17 with other diseases. In cohort I, the three best US measures showed higher mean ± SD areas under the curve than the respective NCS measures (0.99 ± 0.01 vs. 0.79 ± 0.03, p < 0.001; two-sided t test). The US model with highest measurement efficacy (8 values) and diagnostic quality reached 100 % sensitivity and 92 % specificity for MMN in cohort II, while the respective NCS model (6 values, including presence of conduction blocks) reached 100 and 52 %. Nerve US is of high diagnostic accuracy for differential diagnosis of ALS/LMND and MMN. It might be superior to NCS in the diagnosis of MMN in hospital-admitted patients with this differential diagnosis.