New articles from Prof. Heinz Reichmann, our Associate Editor

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles from Prof. Heinz Reichmann, our Associate Editor.

Title: Rotigotine Transdermal Patch for Motor and Non-motor Parkinson’s Disease: A Review of 12 Years’ Clinical Experience
Authors: Vanessa Raeder, Iro Boura, Valentina Leta, Peter Jenner, Heinz Reichmann, Claudia Trenkwalder, Lisa Klingelhoefer, K. Ray Chaudhuri
Type: Review Article from CNS Drugs
Abstract:
Motor and non-motor symptoms (NMS) have a substantial effect on the health-related quality of life (QoL) of patients with Parkinson's disease (PD). Transdermal therapy has emerged as a time-tested practical treatment option, and the rotigotine patch has been used worldwide as an alternative to conventional oral treatment for PD. The efficacy of rotigotine on motor aspects of PD, as well as its safety and tolerability profile, are well-established, whereas its effects on a wide range of NMS have been described and studied but are not widely appreciated. In this review, we present our overall experience with rotigotine and its tolerability and make recommendations for its use in PD and restless legs syndrome, with a specific focus on NMS, underpinned by level 1–4 evidence. We believe that the effective use of the rotigotine transdermal patch can address motor symptoms and a wide range of NMS, improving health-related QoL for patients with PD. More specifically, the positive effects of rotigotine on non-motor fluctuations are also relevant. We also discuss the additional advantages of the transdermal application of rotigotine when oral therapy cannot be used, for instance in acute medical emergencies or nil-by-mouth or pre/post-surgical scenarios. We highlight evidence to support the use of rotigotine in selected cases (in addition to general use for motor benefit) in the context of personalised medicine.
Access this article: https://doi.org/10.1007/s40263-020-00788-4

Title: Emotional well-being and pain could be a greater determinant of quality of life compared to motor severity in cervical dystonia
Authors: Lisa Klingelhoefer, Maximilian Kaiser, Anna Sauerbier, Robert Untucht, Miriam Wienecke, Könül Mammadova, Björn Falkenburger, Olaf Gregor, K. Ray Chaudhuri, Heinz Reichmann
Type: Original Article of Journal of Neural Transmission
Abstract:
Non-motor symptoms (NMS) occur in patients with cervical dystonia (CD) but with variable frequencies and impact on health-related quality of life (HRQoL). To define non-motor and motor profiles and their respective impact on HRQoL in CD patients using the newly validated Dystonia Non-Motor Symptoms Questionnaire (DNMSQuest). In an observational prospective multicentre case–control study, we enrolled 61 patients with CD and 61 age- and sex-matched healthy controls (HC) comparing demographic data, motor and non-motor symptoms and HRQoL measurements. 95% CD patients reported at least one NMS. Mean total NMS score was significantly higher in CD patients (5.62 ± 3.33) than in HC (1.74 ± 1.52; p < 0.001). Pain, insomnia and stigma were the most prevalent NMS and HRQoL was significantly impaired in CD patients compared to HC. There was strong correlation of NMS burden with HRQoL (CDQ-24: r = 0.72, EQ-5D: r = − 0.59; p < 0.001) in CD patients. Regression analysis between HRQoL and NMS suggested that emotional well-being (standardized beta = − 0.352) and pain (standardized beta = − 0.291) had a major impact on HRQoL while, in contrast motor severity had no significant impact in this model. Most NMS with the exception of pain, stigma and ADL did not correlate with motor severity. NMS are highly prevalent in CD patients and occur independent of age, sex, disease duration, duration of botulinum neurotoxin therapy and socio-economic status. Specific NMS such as emotional well-being and pain have a major impact on HRQoL and are more relevant than motor severity.
Access this article: https://doi.org/10.1007/s00702-020-02274-z

Title: One nerve suffices: A clinically guided nerve ultrasound protocol for the differentiation of multifocal motor neuropathy (MMN) and amyotrophic lateral sclerosis (ALS)
Authors: Kai F. Loewenbrück, Robin Werner, René Günther, Markus Dittrich, Robert Klingenberger, Heinz Reichmann, Alexander Storch, Andreas Hermann
Type: Original Communication of Journal of Neurology
Access this article: https://doi.org/10.1007/s00415-020-10323-6

Title: Assessment of real life eating difficulties in Parkinson’s disease patients by measuring plate to mouth movement elongation with inertial sensors
Authors: Konstantinos Kyritsis, Petter Fagerberg, Ioannis Ioakimidis, K. Ray Chaudhuri, Heinz Reichmann, Lisa Klingelhoefer, Anastasios Delopoulos
Type: Article of Scientific Reports
Abstract:
Parkinson’s disease (PD) is a neurodegenerative disorder with both motor and non-motor symptoms. Despite the progressive nature of PD, early diagnosis, tracking the disease’s natural history and measuring the drug response are factors that play a major role in determining the quality of life of the affected individual. Apart from the common motor symptoms, i.e., tremor at rest, rigidity and bradykinesia, studies suggest that PD is associated with disturbances in eating behavior and energy intake. Specifically, PD is associated with drug-induced impulsive eating disorders such as binge eating, appetite-related non-motor issues such as weight loss and/or gain as well as dysphagia—factors that correlate with difficulties in completing day-to-day eating-related tasks. In this work we introduce Plate-to-Mouth (PtM), an indicator that relates with the time spent for the hand operating the utensil to transfer a quantity of food from the plate into the mouth during the course of a meal. We propose a two-step approach towards the objective calculation of PtM. Initially, we use the 3D acceleration and orientation velocity signals from an off-the-shelf smartwatch to detect the bite moments and upwards wrist micromovements that occur during a meal session. Afterwards, we process the upwards hand micromovements that appear prior to every detected bite during the meal in order to estimate the bite’s PtM duration. Finally, we use a density-based scheme to estimate the PtM durations distribution and form the in-meal eating behavior profile of the subject. In the results section, we provide validation for every step of the process independently, as well as showcase our findings using a total of three datasets, one collected in a controlled clinical setting using standardized meals (with a total of 28 meal sessions from 7 Healthy Controls (HC) and 21 PD patients) and two collected in-the-wild under free living conditions (37 meals from 4 HC/10 PD patients and 629 meals from 3 HC/3 PD patients, respectively). Experimental results reveal an Area Under the Curve (AUC) of 0.748 for the clinical dataset and 0.775/1.000 for the in-the-wild datasets towards the classification of in-meal eating behavior profiles to the PD or HC group. This is the first work that attempts to use wearable Inertial Measurement Unit (IMU) sensor data, collected both in clinical and in-the-wild settings, towards the extraction of an objective eating behavior indicator for PD.
Access this article: https://doi.org/10.1038/s41598-020-80394-y

Title: Assistive HCI-Serious Games Co-design Insights: The Case Study of i-PROGNOSIS Personalized Game Suite for Parkinson’s Disease
Authors: Sofia Balula Dias, José Alves Diniz, Evdokimos Konstantinidis, Theodore Savvidis, Vicky Zilidou, Panagiotis D. Bamidis, Athina Grammatikopoulou, Kosmas Dimitropoulos, Nikos Grammalidis, Hagen Jaeger, Michael Stadtschnitzer, Hugo Silva, Gonçalo Telo, Ioannis Ioakeimidis, George Ntakakis, Fotis Karayiannis, Estelle Huchet, Vera Hoermann, Konstantinos Filis, Elina Theodoropoulou, George Lyberopoulos, Konstantinos Kyritsis, Alexandros Papadopoulos, Anastasios Depoulos, Dhaval Trivedi, Ray K. Chaudhuri, Lisa Klingelhoefer, Heinz Reichmann, Sevasti Bostantzopoulou, Zoe Katsarou, Dimitrios Iakovakis14, Stelios Hadjidimitriou, Vasileios Charisis, George Apostolidis, Leontios J. Hadjileontiadis
Type: Original Research Article of Frontiers in Psychology
Abstract:
Human-Computer Interaction (HCI) and games set a new domain in understanding people’s motivations in gaming, behavioral implications of game play, game adaptation to player preferences and needs for increased engaging experiences in the context of HCI serious games (HCI-SGs). When the latter relate with people’s health status, they can become a part of their daily life as assistive health status monitoring/enhancement systems. Co-designing HCI-SGs can be seen as a combination of art and science that involves a meticulous collaborative process. The design elements in assistive HCI-SGs for Parkinson’s Disease (PD) patients, in particular, are explored in the present work. Within this context, the Game-Based Learning (GBL) design framework is adopted here and its main game-design parameters are explored for the Exergames, Dietarygames, Emotional games, Handwriting games, and Voice games design, drawn from the PD-related i-PROGNOSIS Personalized Game Suite (PGS) (www.i-prognosis.eu) holistic approach. Two main data sources were involved in the study. In particular, the first one includes qualitative data from semi-structured interviews, involving 10 PD patients and four clinicians in the co-creation process of the game design, whereas the second one relates with data from an online questionnaire addressed by 104 participants spanning the whole related spectrum, i.e., PD patients, physicians, software/game developers. Linear regression analysis was employed to identify an adapted GBL framework with the most significant game-design parameters, which efficiently predict the transferability of the PGS beneficial effect to real-life, addressing functional PD symptoms. The findings of this work can assist HCI-SG designers for designing PD-related HCI-SGs, as the most significant game-design factors were identified, in terms of adding value to the role of HCI-SGs in increasing PD patients’ quality of life, optimizing the interaction with personalized HCI-SGs and, hence, fostering a collaborative human-computer symbiosis.
Access this article: https://doi.org/10.3389/fpsyg.2020.612835

Title: Pathophysiological Changes in the Enteric Nervous System of Rotenone-Exposed Mice as Early Radiological Markers for Parkinson's Disease
Authors: Gabriela Schaffernicht, Qi Shang, Alicia Stievenard, Kai Bötzel1, Yanina Dening, Romy Kempe, Magali Toussaint, Daniel Gündel, Mathias Kranz, Heinz Reichmann, Christel Vanbesien-Mailliot, Peter Brust, Marianne Dieterich, Richard H. W. Funk, Ursula Ravens, Francisco Pan-Montojo
Type: Original Research article of Frontiers in Neurology
Abstract:
Parkinson's disease (PD) is known to involve the peripheral nervous system (PNS) and the enteric nervous system (ENS). Functional changes in PNS and ENS appear early in the course of the disease and are responsible for some of the non-motor symptoms observed in PD patients like constipation, that can precede the appearance of motor symptoms by years. Here we analyzed the effect of the pesticide rotenone, a mitochondrial Complex I inhibitor, on the function and neuronal composition of the ENS by measuring intestinal contractility in a tissue bath and by analyzing related protein expression. Our results show that rotenone changes the normal physiological response of the intestine to carbachol, dopamine and electric field stimulation (EFS). Changes in the reaction to EFS seem to be related to the reduction in the cholinergic input but also related to the noradrenergic input, as suggested by the non-adrenergic non-cholinergic (NANC) reaction to the EFS in rotenone-exposed mice. The magnitude and direction of these alterations varies between intestinal regions and exposure times and is associated with an early up-regulation of dopaminergic, cholinergic and adrenergic receptors and an irregular reduction in the amount of enteric neurons in rotenone-exposed mice. The early appearance of these alterations, that start occurring before the substantia nigra is affected in this mouse model, suggests that these alterations could be also observed in patients before the onset of motor symptoms and makes them ideal potential candidates to be used as radiological markers for the detection of Parkinson's disease in its early stages.
Access this article: https://doi.org/10.3389/fneur.2021.642604