Erfassung und Trainierbarkeit der posturalen Kontrolle und Modulation des Gangbildes bei Patienten mit Morbus Parkinson

Die vorliegende Arbeit gliedert sich in drei Teile. Zunächst geht es um die Erfassung der posturalen Instabilität bei Patienten mit Morbus Parkinson. Es wurde ein klinischer Gleichgewichtstest (Fullerton Advanced Balance (FAB) Scale) zur Erhebung der posturalen Kontrolle validiert und mit der Berg Balance Scale und dem Mini-Balance Evaluation System Test (Mini-BESTest) verglichen. Hierfür wurden 85 Parkinsonpatienten eingeschlossen und untersucht. Es konnte gezeigt werden, dass die FAB Scale ein valides und hoch reliables Messinstrument ist. Ein Deckeneffekt kann durch die FAB Scale vermieden werden. Trotz der differenzierten Skala ist die FAB Scale genauso reliabel wie der Mini-BESTest. Der Test ist schneller durchführbar als die Berg Balance Scale und der Mini-BESTest. Der zweite Teil befasst sich mit der Frage inwiefern sich die posturale Kontrolle durch Training verbessern lässt. In einer randomisiert kontrollierten Rater-verblindeten Studie wurde hierzu ein Krafttraining mit einem Balance-Training zur Steigerung der posturalen Kontrolle bei Patienten mit Morbus Parkinson verglichen. 40 Patienten wurden eingeschlossen und absolvierten ein 7-wöchiges Kraft- oder Balance-Training. Die posturale Kontrolle konnte durch Krafttraining – jedoch nicht durch Balance-Training – verbessert werden. Es gab keinen signifikanten Unterschied beim Vergleich der Therapieeffekte beider Trainingsformen. Die Studie zeigt Tendenzen, dass Krafttraining effektiver ist als Balance-Training. Zudem konnte ein Zusammenhang zwischen der Steigerung der posturalen Kontrolle und der Verbesserung der Explosivkraft gezeigt werden. Schließlich wird im letzten Teil die Gangstörung bei Patienten mit Morbus Parkinson behandelt. Wie sich das Gangbild durch das asymmetrische Gehen auf einem Split-Belt-Laufband modulieren lässt, war Gegenstand dieser Studie. Bei 20 Patienten wurde das Gangbild unter verschiedenen Split-Belt-Laufbandbedingungen untersucht. Nach einer 10-minütigen Phase mit Reduzierung der Bandgeschwindigkeit des Beines mit der größeren Schrittlänge, konnten mehrere Gangvariablen, die in Zusammenhang mit Gangblockaden (Freezing) stehen, verbessert werden. Die Studie zeigt, dass Split-Belt-Laufbandtraining ein wichtiger Ansatz zur Verbesserung des Gangbildes sowie zur Reduzierung der Freezing-Häufigkeit ist

Surface Modification of Membranes for Fouling Reduction

Despite great effort that has been made to reduce and understand fouling, this phenomenon is still a major problem in membrane applications. Numerous methods, both from a chemical and engineering point of view, have been introduced to overcome this problem. In this contribution, we report on the modification of membranes with polyelectrolytes and polyelectrolyte multilayers utilizing two of the mentioned strategies. The effect of surface modification on the fouling behavior as well as on the critical flux will be discussed on two examples, microfiltration membranes and RO membranes

Ribonucleoparticle-independent transport of proteins into mammalian microsomes

There are at least two different mechanisms for the transport of secretory proteins into the mammalian endoplasmic reticulum. Both mechanisms depend on the presence of a signal peptide on the respective precursor protein and involve a signal peptide receptor on the cis-side and signal peptidase on the trans-side of the membrane. Furthermore, both mechanisms involve a membrane component with a cytoplasmically exposed sulfhydryl. The decisive feature of the precursor protein with respect to which of the two mechanisms is used is the chain length of the polypeptide. The critical size seems to be around 70 amino acid residues (including the signal peptide). The one mechanism is used by precursor proteins larger than about 70 amino acid residues and involves two cytosolic ribonucleoparticles and their receptors on the microsomal surface. The other one is used by small precursor proteins and relies on the mature part within the precursor molecule and a cytosolic ATPase

Moderate Frequency Resistance and Balance Training Do Not Improve Freezing of Gait in Parkinson's Disease: A Pilot Study

Background and Aim: Individuals with Parkinson's disease (PD) and Freezing of Gait (FOG) have impaired postural control, which relate to the severity of FOG. The aim of this study was to analyze whether a moderate frequency resistance (RT) and balance training (BT), respectively, are effective to diminish FOG.Methods: This post-hoc sub-analysis of a randomized controlled training intervention study of PD patients with and without FOG reports about results from FOG patients. Twelve FOG patients performed RT and 8 BT (training 2x/week, 7 weeks). Testing was performed prior and post intervention. FOG was assessed with the FOG Questionnaire (FOGQ) and with the FOG score of a FOG provoking walking course. Balance performance was evaluated with the Fullerton Advanced Balance (FAB) scale. Tests were conducted by raters blinded to group allocation and assessment time point (only FOG score and FAB scale).Results: For the FOGQ and FOG score, no significant differences were found within and between the two training groups (p > 0.05) and effect sizes for the improvements were small (r < 0.1). Groups did not significantly improve in the FAB scale. FOG score changes and FAB scale changes within the RT group showed a trend toward significant negative correlation (Rho = −0.553, p = 0.098).Conclusions: Moderate frequency RT and BT was not effective in reducing FOG in this pilot study. The trend toward negative correlation between changes in FOG score and FAB scale suggests an interaction between balance (improvement) and FOG (improvement). Future studies should include larger samples and high frequency interventions to investigate the role of training balance performance to reduce the severity of FOG

Validation of a Lower Back “Wearable”-Based Sit-to-Stand and Stand-to-Sit Algorithm for Patients With Parkinson's Disease and Older Adults in a Home-Like Environment

Introduction: Impaired sit-to-stand and stand-to-sit movements (postural transitions, PTs) in patients with Parkinson’s disease (PD) and older adults (OA) are associated with risk of falling and reduced quality of life. Inertial measurement units (IMUs, also called “wearables”) are powerful tools to monitor PT kinematics. The purpose of this study was to develop and validate an algorithm, based on a single IMU positioned at the lower back, for PT detection and description in the above-mentioned groups in a home-like environment. Methods: Four PD patients (two with dyskinesia) and one OA served as algorithm training group, and 21 PD patients (16 without and 5 with dyskinesia) and 11 OA served as test group. All wore an IMU on the lower back and were videotaped while performing everyday activities for 90–180min in a non-standardized home-like environment. Accelerometer and gyroscope signals were analyzed using discrete wavelet transformation (DWT), a six degrees-of-freedom (DOF) fusion algorithm and vertical displacement estimation. Results: From the test group, 1,001 PTs, defined by video reference, were analyzed. The accuracy of the algorithm for the detection of PTs against video observation was 82% for PD patients without dyskinesia, 47% for PD patients with dyskinesia and 85% for OA. The overall accuracy of the PT direction detection was comparable across groups and yielded 98%. Mean PT duration values were 1.96 s for PD patients and 1.74 s for OA based on the algorithm (p < 0.001) and 1.77 s for PD patients and 1.51 s for OA based on clinical observation (p < 0.001). Conclusion: Validation of the PT detection algorithm in a home-like environment shows acceptable accuracy against the video reference in PD patients without dyskinesia and controls. Current limitations are the PT detection in PD patients with dyskinesia and the use of video observation as the video reference. Potential reasons are discussed

Validation of a Lower Back “Wearable”-Based Sit-to-Stand and Stand-to-Sit Algorithm for Patients With Parkinson's Disease and Older Adults in a Home-Like Environment

Introduction: Impaired sit-to-stand and stand-to-sit movements (postural transitions, PTs) in patients with Parkinson's disease (PD) and older adults (OA) are associated with risk of falling and reduced quality of life. Inertial measurement units (IMUs, also called “wearables”) are powerful tools to monitor PT kinematics. The purpose of this study was to develop and validate an algorithm, based on a single IMU positioned at the lower back, for PT detection and description in the above-mentioned groups in a home-like environment.Methods: Four PD patients (two with dyskinesia) and one OA served as algorithm training group, and 21 PD patients (16 without and 5 with dyskinesia) and 11 OA served as test group. All wore an IMU on the lower back and were videotaped while performing everyday activities for 90–180 min in a non-standardized home-like environment. Accelerometer and gyroscope signals were analyzed using discrete wavelet transformation (DWT), a six degrees-of-freedom (DOF) fusion algorithm and vertical displacement estimation.Results: From the test group, 1,001 PTs, defined by video reference, were analyzed. The accuracy of the algorithm for the detection of PTs against video observation was 82% for PD patients without dyskinesia, 47% for PD patients with dyskinesia and 85% for OA. The overall accuracy of the PT direction detection was comparable across groups and yielded 98%. Mean PT duration values were 1.96 s for PD patients and 1.74 s for OA based on the algorithm (p &lt; 0.001) and 1.77 s for PD patients and 1.51 s for OA based on clinical observation (p &lt; 0.001).Conclusion: Validation of the PT detection algorithm in a home-like environment shows acceptable accuracy against the video reference in PD patients without dyskinesia and controls. Current limitations are the PT detection in PD patients with dyskinesia and the use of video observation as the video reference. Potential reasons are discussed

Connecting real-world digital mobility assessment to clinical outcomes for regulatory and clinical endorsement–the Mobilise-D study protocol

Background: The development of optimal strategies to treat impaired mobility related to ageing and chronic disease requires better ways to detect and measure it. Digital health technology, including body worn sensors, has the potential to directly and accurately capture real-world mobility. Mobilise-D consists of 34 partners from 13 countries who are working together to jointly develop and implement a digital mobility assessment solution to demonstrate that real-world digital mobility outcomes have the potential to provide a better, safer, and quicker way to assess, monitor, and predict the efficacy of new interventions on impaired mobility. The overarching objective of the study is to establish the clinical validity of digital outcomes in patient populations impacted by mobility challenges, and to support engagement with regulatory and health technology agencies towards acceptance of digital mobility assessment in regulatory and health technology assessment decisions. Methods/design: The Mobilise-D clinical validation study is a longitudinal observational cohort study that will recruit 2400 participants from four clinical cohorts. The populations of the Innovative Medicine Initiative-Joint Undertaking represent neurodegenerative conditions (Parkinson’s Disease), respiratory disease (Chronic Obstructive Pulmonary Disease), neuro-inflammatory disorder (Multiple Sclerosis), fall-related injuries, osteoporosis, sarcopenia, and frailty (Proximal Femoral Fracture). In total, 17 clinical sites in ten countries will recruit participants who will be evaluated every six months over a period of two years. A wide range of core and cohort specific outcome measures will be collected, spanning patient-reported, observer-reported, and clinician-reported outcomes as well as performance-based outcomes (physical measures and cognitive/mental measures). Daily-living mobility and physical capacity will be assessed directly using a wearable device. These four clinical cohorts were chosen to obtain generalizable clinical findings, including diverse clinical, cultural, geographical, and age representation. The disease cohorts include a broad and heterogeneous range of subject characteristics with varying chronic care needs, and represent different trajectories of mobility disability. Discussion: The results of Mobilise-D will provide longitudinal data on the use of digital mobility outcomes to identify, stratify, and monitor disability. This will support the development of widespread, cost-effective access to optimal clinical mobility management through personalised healthcare. Further, Mobilise-D will provide evidence-based, direct measures which can be endorsed by regulatory agencies and health technology assessment bodies to quantify the impact of disease-modifying interventions on mobility. Trial registration: ISRCTN12051706

Are Hypometric Anticipatory Postural Adjustments Contributing to Freezing of Gait in Parkinson’s Disease?

Introduction: This study aims at investigating whether impaired anticipatory postural adjustments (APA) during gait initiation contribute to the occurrence of freezing of gait (FOG) or whether altered APAs compensate for FOG in Parkinson’s disease (PD).Methods: Gait initiation after 30 s quiet stance was analyzed without and with a cognitive dual task (DT) in 33 PD subjects with FOG (PD+FOG), 30 PD subjects without FOG (PD-FOG), and 32 healthy controls (HC). APAs were characterized with inertial sensors and muscle activity of the tensor fasciae latae (TFL), gastrocnemius, and tibialis anterior was captured with electromyography recordings. Nine trials (of 190) were associated with start hesitation/FOG and analyzed separately.Results: PD+FOG and PD-FOG did not differ in disease duration, disease severity, age, or gender. PD+FOG had significantly smaller medio-lateral (ML) and anterio-posterior APAs compared to PD-FOG (DT, p &lt; 0.05). PD+FOG had more co-contraction of left and right TFL during APAs compared to PD-FOG (p &lt; 0.01). Within the PD+FOG, the ML size of APA (DT) was positively correlated with the severity of FOG history (NFOG-Q), with larger APAs associated with worse FOG (rho = 0.477, p = 0.025). ML APAs were larger during trials with observed FOG compared to trials of PD+FOG without FOG.Conclusions: People with PD who have a history of FOG have smaller ML APAs (weight shifting) during gait initiation compared to PD-FOG and HC. However, start hesitation (FOG) is not caused by an inability to sufficiently displace the center of mass toward the stance leg because APAs were larger during trials with observed FOG. We speculate that reducing the acceleration of the body center of mass with hip abductor co-contraction for APAs might be a compensatory strategy in PD+FOG, to address postural control deficits and enable step initiation

Reliability and normalization of long-term versus substituted electromyography electrodes set-ups

Normalization methods are used to minimize the influence of external disturbances in the analysis of myo-electrical signals. Whether these methods actually minimize the error or only relocate it has not been evaluated so far. This verification is only possible in comparison to constant discharge conditions. The aims of this study were (I) to compare the inter-day test-retest reliability of myo-electrical signals from long-term with substituted electrodes and (II) the impact of different normalization methods on test-retest reliability. Myo-electrical activity of the tibialis anterior (TA) and vastus medialis (VA) was recorded from 14 cyclists during 1min cycling with permanent and substituted electrodes and then normalized by selected methods. A good reliability (ICC>0.86) was shown for both muscles with the long-term electrodes whereas poor reliability (ICC=0.32) was found for the substituted electrodes set-up (VM). Only the sprint normalization improved the reliability of the long-term electrode set-up, while the other functional approaches improved at least the reliability from substituted electrodes. Only the sprint method achieved the reliability of permanently attached electrodes. Thus, the results rather suggest the use of permanent electrode set ups. If this is not possible due to the study design, the use of functional normalization procedures is recommended.Los métodos de normalización se utilizan para minimizar la influencia de las perturbaciones externas en el análisis de señales mioeléctricas. No se ha evaluado hasta el momento si estos métodos realmente minimizan el error o solo lo reubican. Esta verificación solo es posible en comparación con las condiciones de descarga constantes. Los objetivos de este estudio fueron (I) comparar la fiabilidad test-retest de señales mioeléctricas de larga duración con electrodos desechables y (II) el impacto de diferentes métodos de normalización en la fiabilidad test-retest. La actividad mioeléctrica del tibial anterior (TA) y el vasto medial (VA) se recogió de 14 ciclistas, durante un ciclo de 1min con electrodos de larga duración y desechables y luego se normalizó mediante métodos seleccionados. Se observó una buena fiabilidad (ICC> 0,86) para ambos músculos con los electrodos de larga duración, mientras que se encontró una fiabilidad deficiente (ICC = 0,32) para la configuración de los electrodos desechables (VM). Solamente la normalización del sprint mejoró la confiabilidad de la configuración del electrodo de larga duración, mientras que los otros enfoques funcionales mejoraron al menos la confiabilidad de los electrodos desechables. Solo el método de sprint logró la fiabilidad de los electrodos conectados permanentemente. Por lo tanto, los resultados sugieren más bien el uso de configuraciones permanentes de electrodos. Si esto no es posible debido al diseño del estudio, se recomienda el uso de procedimientos de normalización funcional

Can split-belt treadmill training improve dual-task turning performance in patients with Parkinson’s disease with Freezing of gait

BACKGROUND AND AIM: Motor-cognitive dual tasks (DT) pose several difficulties for patients with Parkinson’s disease with Freezing of gait (PD+FOG) as it requires continuous adaptation and switching of attention. Targeted motor-cognitive DT training has been shown to improve DT performance in PD+FOG with limited retention and transfer effects. Split-belt treadmill training (SBT) implicitly requires online monitoring and adaptation of gait, however the potential to induce learning and influence DT performance is unknown. Therefore in this study, we investigated whether motor adaptation training by means of SBT could improve motor-cognitive DT performance in PD+FOG. METHODS: To date, thirty-nine PD patients with FOG and twenty-seven age-matched healthy controls (HC) participated in a single training session at two centers (KU Leuven, Belgium and CAU of Kiel, Germany). They were randomized to four 30-minutes (6x5min) intervention groups: A) SBT belts’ speed ratio 1:2; B) SBT belts’ speed ratio 3:4; C) SBT changing belts’ speed ratios; D) Tied-Belt. For the SBT conditions (A-C) the belt's speed was reduced of the leg with the longer step length measured during overground gait analysis. A one-minute 360° turning at the spot test with alternating directions and while simultaneously performing an auditory stroop task was performed pre- and post-training as well as at 24h retention. A linear mixed models analysis was applied to investigate the effect of training condition over time. RESULTS: Preliminary analysis showed that PD+FOG and HC both improved in DT Turning from Pre-training to 24h Retention (DT Peak Turning Speed: Main effect of Time F=6.07; p>0.01; Relative change from baseline to Retention: PD+FOG 6.1%; HC 7.9%). Although PD+FOG showed deterioration from Pre- to Post-training, likely due to fatigue and dopamine exhaustion, offline consolidation was preserved (DT Peak Turning Speed: Post-training to Retention – relative change: PD+FOG 8.1% vs HC 2.6%). Performance on the auditory Stroop task also showed improvements from Pre-training to retention, trending towards greater improvements for SBT vs Tied Belt training in the whole group (Faster Response Time – Training*Time effect F=1.59; p=0.22; relative change from Baseline to retention 3.3%) and for PD+FOG subgroup (Lower Response Time variability – Training*Time effect F=2.09; p=0.16 ; relative change from Baseline to retention 7.6%) CONCLUSIONS: A single SBT session was seen to induce learning in HC as well as PD+FOG, with motor adaptation effects showing trends of transfer and automaticity to DT turning situation. This improved automaticity possibly frees up attentional resources as improvements were found in the cognitive task as well. Future work should investigate these mechanisms as well as the longer term effects of SBT on motor-cognitive DT performance.status: publishe