Quantitative Messung vom Gehen auf der Stelle zur Erhebung von motorischen Symptomen bei Morbus Parkinson

Fluctuating motor symptoms are one of the main challenges in the assessment and evaluation of treatment effects in Parkinson’s disease (PD). The stepping in place task was previously proposed as an assessment of postural control and as surrogate for gait tests, two important evaluations of disturbed motor functions in this disorder. Due to its low spatial requirement, this motor task might specifically be suitable for an instrumental assessment even in remote application. Objective of this study was to explore the quantification of motor features associated with Parkinson's Diseases during stepping in place performance. Methods: Performance of 40 sec stepping in place (SIP) was recorded with a marker-free motion analysis system using a single RGB-Depth camera system. Data from 25 Persons with PD (PwPD, 7 female, Age: mean 65.3 years ± 9.4 years, MDS-UPDRS III 5-65) in up to two different treatment states (OFF: 13, ON: 20) and data from 83 healthy controls (HC, 52 female, Age: 36.8y ± 13.8y) was available for algorithm development, feature extraction and statistical analysis. Based on knee movements, eight spatiotemporal parameters were extracted including cadence, average knee movement amplitude, average and longest step and stance times, asymmetry and arrhythmicity. Parameters were analysed regarding potential confounding effects, technical accuracy and repeatability in HC, their relation to disease severity (MDS-UPDRS III) and postural instability (pull test score) in PwPD and intra- individual differences in treatment states (OFF vs. ON). Results: Six out of eight features showed good accuracy and repeatability in HC subgroup (n=19). Asymmetry and arrhythmicity showed only poor to moderate accuracy (ICC(A,1) > .3; Pearson’s r > .5) and repeatability (ICC(1,1) >.4). No linear confounding effects of age, height and weight were found in HC and PwPD. Decreased knee amplitude was associated with higher disease severity (rho = -.503, p-value = .003) and higher postural instability (rho = - .436, p-value = .014). Knee amplitudes showed also increase of 85.4% from OFF to ON in a subgroup in which recordings were available from both treatment states (n=10). Longer stance time measures were associated with higher disease severity (rho = .523, p-value = .002) and higher postural instability (rho = .468, p-value = .008). 50% of patients with ratings of freezing of gait during MDS-UPDRS III assessment showed freezing during SIP. Conclusion: Instrumental assessment of a 40 sec stepping in place performance may be suitable to quantify common motor symptoms, specifically postural instability, in PwPD. Derived parameters described motor symptoms of PD including decreased ranges of motion (hypokinesia), slower motions (bradykinesia) and increased asymmetry as well as arrhythmicity of stepping movements during SIP. Sensitivity to intra-individual changes, indicates potential use of SIP to monitor fluctuation of motor symptoms in PD.Motorische Fluktuationen sind eine der größten Herausforderungen bei der Beurteilung von Behandlungseffekten bei Morbus Parkinson (PD). Das auf der Stelle Gehen (SIP), wurde ursprünglich als Test zur Haltungskontrolle und als Surrogat für Ganganalyse vorgeschlagen, zwei wichtige Aspekte der gestörten motorischen Funktionen bei Parkinson. Ziel dieser Studie war es, die Quantifizierung von Parkinson-assoziierten motorischen Merkmalen während des Gehens auf der Stelle zu untersuchen. Methoden: Ein makerfreies Bewegungsanalysesystem (RGB-Tiefenkamera) wurde verwendet, um die Ausführung vom SIP über 40 Sekunden aufzuzeichnen. Für die Entwicklung der Algorithmen, die Merkmalsextraktion und die statistische Analyse standen Daten von 25 Personen mit Morbus Parkinson (PwPD, 7 weiblich, Alter: 65,3 Jahre ± 9,4 Jahre, MDS-UPDRS III 5-65) in bis zu zwei verschiedenen Therapiezuständen (OFF: 13, ON: 20) und Daten von 83 gesunden Personen (HC, 52 weiblich, Alter: 36,8 Jahre ± 13,8 Jahre) zur Verfügung. Auf Grundlage der Kniebewegungen wurden acht Parameter extrahiert: Kadenz, durchschnittliche Amplitude der Kniebewegung, durchschnittliche und längste Schritt- und Standzeiten, Asymmetrie und Arrhythmie. Die Parameter wurden im Hinblick auf potenzielle Störfaktoren, technische Genauigkeit und Wiederholbarkeit bei HC, Zusammenhang mit dem Schweregrad der Erkrankung (MDS-UPDRS III) und der posturalen Instabilität (Pull-Test-Score) in PwPD sowie auf intraindividuelle Unterschiede bei den Behandlungszuständen (OFF vs. ON) analysiert. Ergebnisse: Sechs von acht Merkmalen zeigten eine gute Genauigkeit und Wiederholbarkeit in HC (n=19). Asymmetrie und Arrhythmie zeigten nur geringe bis mäßige Genauigkeit (ICC(A,1) > .3; Pearson's r > .5) und Wiederholbarkeit (ICC(1,1) >.4). Bei HC (n=83) und PwPD (n=33) wurden keine linearen Effekte von Alter, Größe und Gewicht festgestellt. Eine verringerte Knieamplitude war mit höherer Krankheitsschwere (rho=-.503, p-Wert = .003) und höherer posturalen Instabilität (rho=-.436, p-Wert=.014) verbunden. Die Knieamplituden nahmen in einer Untergruppe (n=10), von OFF zu ON um 85,4 % zu. Längere Standzeiten waren mit höherer Krankheitsschwere (rho=.523, p-Wert=.002) und höherer posturalen Instabilität (rho=.468, p-Wert=.008) verbunden. 50 % der Patienten, die im MDS-UPDRS-III ein Einfrieren des Gangs zeigten, zeigten auch beim SIP ein Einfrieren. Schlussfolgerung: Die instrumentelle Analyse vom 40-sekündigen Gehen auf der Stelle kann geeignet sein, häufige motorische Symptome, insbesondere posturale Instabilität, bei PwPD zu quantifizieren. Die abgeleiteten Parameter beschrieben die motorischen Symptome von Morbus Parkinson, einschließlich verringerten Bewegungsumfang (Hypokinese), langsamerer Bewegungen (Bradykinese) und Asymmetrie sowie Arrhythmie der Schrittbewegungen. Die Empfindlichkeit gegenüber intraindividuellen Veränderungen deutet auf einen möglichen Einsatz des SIP zum Monitoring motorischer Symptome von PD hin

Using New Camera-Based Technologies for Gait Analysis in Older Adults in Comparison to the Established GAITRite System

Various gait parameters can be used to assess the risk of falling in older adults. However, the state-of-the-art systems used to quantify gait parameters often come with high costs as well as training and space requirements. Gait analysis systems, which use mobile and commercially available cameras, can be an easily available, marker-free alternative. In a study with 44 participants (age ≥ 65 years), gait patterns were analyzed with three different systems: a pressure sensitive walkway system (GAITRite-System, GS) as gold standard, Motognosis Labs Software using a Microsoft Kinect Sensor (MKS), and a smartphone camera-based application (SCA). Intertrial repeatability showed moderate to excellent results for MKS (ICC(1,1) 0.574 to 0.962) for almost all measured gait parameters and moderate reliability in SCA measures for gait speed (ICC(1,1) 0.526 to 0.535). All gait parameters of MKS showed a high level of agreement with GS (ICC(2,k) 0.811 to 0.981). Gait parameters extracted with SCA showed poor reliability. The tested gait analysis systems based on different camera systems are currently only partially able to capture valid gait parameters. If the underlying algorithms are adapted and camera technology is advancing, it is conceivable that these comparatively simple methods could be used for gait analysis

Contactless recording of sleep apnea and periodic leg movements by nocturnal 3-D-video and subsequent visual perceptive computing

Contactless measurements during the night by a 3-D-camera are less time-consuming in comparison to polysomnography because they do not require sophisticated wiring. However, it is not clear what might be the diagnostic benefit and accuracy of this technology. We investigated 59 persons simultaneously by polysomnography and 3-D-camera and visual perceptive computing (19 patients with restless legs syndrome (RLS), 21 patients with obstructive sleep apnea (OSA), and 19 healthy volunteers). There was a significant correlation between the apnea hypopnea index (AHI) measured by polysomnography and respiratory events measured with the 3-D-camera in OSA patients (r = 0.823; p < 0.001). The receiver operating characteristic curve yielded a sensitivity of 90% for OSA with a specificity of 71.4%. In RLS patients 72.8% of leg movements confirmed by polysomnography could be detected by 3-D-video and a significant moderate correlation was found between PLM measured by polysomnography and by the 3-D-camera (RLS: r = 0.654; p = 0.004). In total, 95.4% of the sleep epochs were correctly classified by the machine learning approach, but only 32.5% of awake epochs. Further studies should investigate, if this technique might be an alternative to home sleep testing in persons with an increased pre-test probability for OSA

Less Is More - Estimation of the Number of Strides Required to Assess Gait Variability in Spatially Confined Settings

Background: Gait variability is an established marker of gait function that can be assessed using sensor-based approaches. In clinical settings, spatial constraints and patient condition impede the execution of longer distance walks for the recording of gait parameters. Turning paradigms are often used to overcome these constraints and commercial gait analysis systems algorithmically exclude turns for gait parameters calculations. We investigated the effect of turns in sensor-based assessment of gait variability. Methods: Continuous recordings from 31 patients with movement disorders (ataxia, essential tremor and Parkinson's disease) and 162 healthy elderly (HE) performing level walks including 180° turns were obtained using an inertial sensor system. Accuracy of the manufacturer's algorithm of turn-detection was verified by plotting stride time series. Strides before and after turn events were extracted and compared to respective average of all strides. Coefficient of variation (CoV) of stride length and stride time was calculated for entire set of strides, segments between turns and as cumulative values. Their variance and congruency was used to estimate the number of strides required to reliably assess the magnitude of stride variability. Results: Non-detection of turns in 5.8% of HE lead to falsely increased CoV for these individuals. Even after exclusion of these, strides before/after turns tended to be spatially shorter and temporally longer in all groups, contributing to an increase of CoV at group level and widening of confidence margins with increasing numbers of strides. This could be attenuated by a more generous turn excision as an alternative approach. Correlation analyses revealed excellent consistency for CoVs after at most 20 strides in all groups. Respective stride counts were even lower in patients using a more generous turn excision. Conclusion: Including turns to increase continuous walking distance in spatially confined settings does not necessarily improve the validity and reliability of gait variability measures. Specifically with gait pathology, perturbations of stride characteristics before/after algorithmically excised turns were observed that may increase gait variability with this paradigm. We conclude that shorter distance walks of around 15 strides suffice for reliable and valid recordings of gait variability in the groups studied here

Subjective and objective assessment of physical activity in multiple sclerosis and their relation to health-related quality of life

Background Physical activity (PA) is frequently restricted in people with multiple sclerosis (PwMS) and aiming to enhance PA is considered beneficial in this population. We here aimed to explore two standard methods (subjective plus objective) to assess PA reduction in PwMS and to describe the relation of PA to health-related quality of life (hrQoL). Methods PA was objectively measured over a 7-day period in 26 PwMS (EDSS 1.5–6.0) and 30 matched healthy controls (HC) using SenseWear mini® armband (SWAmini) and reported as step count, mean total and activity related energy expenditure (EE) as well as time spent in PA of different intensities. Measures of EE were also derived from self-assessment with IPAQ (International Physical Activity Questionnaire) long version, which additionally yielded information on the context of PA and a classification into subjects’ PA levels. To explore the convergence between both types of assessment, IPAQ categories (low, moderate, high) were related to selected PA parameters from objective assessment using ANOVA. Group differences and associated effect sizes for all PA parameters as well as their relation to clinical and hrQoL measures were determined. Results Both, SWAmini and IPAQ assessment, captured differences in PA between PwMS and HC. IPAQ categories fit well with common cut-offs for step count (p = 0.002) and mean METs (p = 0.004) to determine PA levels with objective devices. Correlations between specifically matched pairs of IPAQ and SWAmini parameters ranged between r .288 and r .507. Concerning hrQoL, the lower limb mobility subscore was related to four PA measures, while a relation with patients’ report of general contentment was only seen for one. Conclusions Both methods of assessment seem applicable in PwMS and able to describe reductions in daily PA at group level. Whether they can be used to track individual effects of interventions to enhance PA levels needs further exploration. The relation of PA measures with hrQoL seen with lower limb mobility suggests lower limb function not only as a major target for intervention to increase PA but also as a possible surrogate for PA changes

MRI Markers and Functional Performance in Patients With CIS and MS: A Cross-Sectional Study

Introduction: Brain atrophy is a widely accepted marker of disease severity with association to clinical disability in multiple sclerosis (MS). It is unclear to which extent this association reflects common age effects on both atrophy and function. Objective: To explore how functional performance in gait, upper extremities and cognition is associated with brain atrophy in patients with Clinically Isolated Syndrome (CIS) and relapsing-remitting MS (RRMS), controlling for effects of age and sex. Methods: In 27 patients with CIS, 59 with RRMS (EDSS <= 3) and 63 healthy controls (HC), 3T MRI were analyzed for T2 lesion count (T2C), volume (T2V) and brain volumes [normalized brain volume (NBV), gray matter volume (NGMV), white matter volume (NWMV), thalamic volume (NThaIV)]. Functional performance was measured with short maximum walking speed (SMSW speed), 9-hole peg test (9HPT) and symbol digit modalities test (SDMT). Linear regression models were created for functional variables with stepwise inclusion of age, sex and MR imaging markers. Results: CIS differed from HC only in T2C and T2V. RRMS differed from HC in NBV, NGMV and NThaIV, T2C and T2V, but not in NWMV. A strong association with age was seen in HC, CIS and RRMS groups for NBV (r = -0.5 to -0.6) and NGMV (r = -0.6 to -0.8). Associations with age were seen in HC and RRMS but not CIS for NThaIV (r = -0.3; r = -0.5), T2C (r(s) = 0.3; r(s) = 0.2) and T2V (r(s) = 0.3; r(s) = 0.3). No effect of age was seen on NWMV. Correlations of functional performance with age in RRMS were seen for SMSW speed, 9HPTand SDMT (r = -0.27 to -0.46). Regression analyses yielded significant models only in the RRMS group for 9HPT, SMSW speed and EDSS. These included NBV, NGMV, NThaIV, NWMV, logT2V, age and sex as predictors. NThalV was the only MRI variable predicting a functional measure (9HPT(r)) with a higher standardized beta than age and sex (R2 = 0.36, p < 1e-04). Conclusion: Thalamic atrophy was a stronger predictor of hand function (9HPT) in RRMS, than age and sex. This underlines the clinical relevance of thalamic atrophy and the relevance of hand function as a clinical marker even in mildly disabled patients

Instrumental Assessment of Stepping in Place Captures Clinically Relevant Motor Symptoms of Parkinson’s Disease

Fluctuations of motor symptoms make clinical assessment in Parkinson's disease a complex task. New technologies aim to quantify motor symptoms, and their remote application holds potential for a closer monitoring of treatment effects. The focus of this study was to explore the potential of a stepping in place task using RGB-Depth (RGBD) camera technology to assess motor symptoms of people with Parkinson's disease. In total, 25 persons performed a 40 s stepping in place task in front of a single RGBD camera (Kinect for Xbox One) in up to two different therapeutic states. Eight kinematic parameters were derived from knee movements to describe features of hypokinesia, asymmetry, and arrhythmicity of stepping. To explore their potential clinical utility, these parameters were analyzed for their Spearman's Rho rank correlation to clinical ratings, and for intraindividual changes between treatment conditions using standard response mean and paired t-test. Test performance not only differed between ON and OFF treatment conditions, but showed moderate correlations to clinical ratings, specifically ratings of postural instability (pull test). Furthermore, the test elicited freezing in some subjects. Results suggest that this single standardized motor task is a promising candidate to assess an array of relevant motor symptoms of Parkinson's disease. The simple technical test setup would allow future use by patients themselves

The Next Generation of Photo-Detector for Particle Astrophysics.

We advocate support of research aimed at developing alternatives to the photomultiplier tube for photon detection in large astroparticle experiments such as gamma-ray and neutrino astronomy, and direct dark matter detectors. Specifically, we discuss the development of large area photocathode microchannel plate photomultipliers and silicon photomultipliers. Both technologies have the potential to exhibit improved photon detection efficiency compared to existing glass vacuum photomultiplier tubes

Recent progress in translational research on neurovascular and neurodegenerative disorders

The already established and widely used intravenous application of recombinant tissue plasminogen activator as a re-opening strategy for acute vessel occlusion in ischemic stroke was recently added by mechanical thrombectomy, representing a fundamental progress in evidence-based medicine to improve the patient’s outcome. This has been paralleled by a swift increase in our understanding of pathomechanisms underlying many neurovascular diseases and most prevalent forms of dementia. Taken together, these current advances offer the potential to overcome almost two decades of marginally successful translational research on stroke and dementia, thereby spurring the entire field of translational neuroscience. Moreover, they may also pave the way for the renaissance of classical neuroprotective paradigms. This review reports and summarizes some of the most interesting and promising recent achievements in neurovascular and dementia research. It highlights sessions from the 9th International Symposium on Neuroprotection and Neurorepair that have been discussed from April 19th to 22nd in Leipzig, Germany. To acknowledge the emerging culture of interdisciplinary collaboration and research, special emphasis is given on translational stories ranging from fundamental research on neurode- and -regeneration to late stage translational or early stage clinical investigations