Progression events defined by home-based assessment of motor function in multiple sclerosis: protocol of a prospective study

BACKGROUND: This study relates to emerging concepts of appropriate trial designs to evaluate effects of intervention on the accumulation of irreversible disability in multiple sclerosis (MS). Major starting points of our study are the known limitations of current definitions of disability progression by rater-based clinical assessment and the high relevance of gait and balance dysfunctions in MS. The study aims to explore a novel definition of disease progression using repeated instrumental assessment of relevant motor functions performed by patients in their home setting. METHODS: The study is a prospective single-center observational cohort study with the primary outcome acquired by participants themselves, a home-based assessment of motor functions based on an RGB-Depth (RGB-D) camera, a camera that provides both depth (D) and color (RGB) data. Participants are instructed to perform and record a set of simple motor tasks twice a day over a one-week period every 6 months. Assessments are complemented by a set of questionnaires. Annual research grade assessments are acquired at dedicated study visits and include clinical ratings as well as structural imaging (MRI and optical coherence tomography). In addition, clinical data from routine visits is provided semiannually by treating neurologists. The observation period is 24 months for the primary endpoint with an additional clinical assessment at 27 month to confirm progression defined by the Expanded Disability Status Scale (EDSS). Secondary analyses aim to explore the time course of changes in motor parameters and performance of the novel definition against different alternative definitions of progression in MS. The study was registered at Deutsches Register für Klinische Studien (DRKS00027042). DISCUSSION: The study design presented here investigates disease progression defined by marker-less home-based assessment of motor functions against 3-month confirmed disease progression (3 m-CDP) defined by the EDSS. The technical approach was chosen due to previous experience in lab-based settings. The observation time per participant of 24, respectively, 27 months is commonly conceived as the lower limit needed to study disability progression. Defining a valid digital motor outcome for disease progression in MS may help to reduce observation times in clinical trials and add confidence to the detection of progression events in MS

RGB-Depth camera-based assessment of motor capacity: normative data for six standardized motor tasks

BACKGROUND: Instrumental motion analysis constitutes a promising development in the assessment of motor function in clinical populations affected by movement disorders. To foster implementation and facilitate interpretation of respective outcomes, we aimed to establish normative data of healthy subjects for a markerless RGB-Depth camera-based motion analysis system and to illustrate their use. METHODS: We recorded 133 healthy adults (56% female) aged 20 to 60 years with an RGB-Depth camera-based motion analysis system. Forty-three spatiotemporal parameters were extracted from six short, standardized motor tasks—including three gait tasks, stepping in place, standing-up and sitting down, and a postural control task. Associations with confounding factors, height, weight, age, and sex were modelled using a predictive linear regression approach. A z-score normalization approach was provided to improve usability of the data. RESULTS: We reported descriptive statistics for each spatiotemporal parameter (mean, standard deviation, coefficient of variation, quartiles). Robust confounding associations emerged for step length and step width in comfortable speed gait only. Accessible normative data usage was lastly exemplified with recordings from one randomly selected individual with multiple sclerosis. CONCLUSION: We provided normative data for an RGB depth camera-based motion analysis system covering broad aspects of motor capacity

Camera-based objective measures of Parkinson's disease gait features

OBJECTIVE: Parkinson's disease is a common, age-related, neurodegenerative disease, affecting gait and other motor functions. Technological developments in consumer imaging are starting to provide high-quality, affordable tools for home-based diagnosis and monitoring. This pilot study aims to investigate whether a consumer depth camera can capture changes in gait features of Parkinson's patients. The dataset consisted of 19 patients (tested in both a practically defined OFF phase and ON phase) and 8 controls, who performed the "Timed-Up-and-Go" test multiple times while being recorded with the Microsoft Kinect V2 sensor. Camera-derived features were step length, average walking speed and mediolateral sway. Motor signs were assessed clinically using the Movement Disorder Society Unified Parkinson's Disease Rating Scale. RESULTS: We found significant group differences between patients and controls for step length and average walking speed, showing the ability to detect Parkinson's features. However, there were no differences between the ON and OFF medication state, so further developments are needed to allow for detection of small intra-individual changes in symptom severity

Cultural bias in motor function patterns: potential relevance for predictive, preventive, and personalized medicine

BACKGROUND: Quantification of motor performance has a promising role in personalized medicine by diagnosing and monitoring, e.g. neurodegenerative diseases or health problems related to aging. New motion assessment technologies can evolve into patient-centered eHealth applications on a global scale to support personalized healthcare as well as treatment of disease. However, uncertainty remains on the limits of generalizability of such data, which is relevant specifically for preventive or predictive applications, using normative datasets to screen for incipient disease manifestations or indicators of individual risks. OBJECTIVE: This study explored differences between healthy German and Japanese adults in the performance of a short set of six motor tests. METHODS: Six motor tasks related to gait and balance were recorded with a validated 3D camera system. Twenty-five healthy adults from Chiba, Japan, participated in this study and were matched for age, sex, and BMI to a sample of 25 healthy adults from Berlin, Germany. Recordings used the same technical setup and standard instructions and were supervised by the same experienced operator. Differences in motor performance were analyzed using multiple linear regressions models, adjusted for differences in body stature. RSEULTS: From 23 presented parameters, five showed group-related differences after adjustment for height and weight (R2 between .19 and .46, p.5) for performance of short comfortable and maximum speed walks. For results of posturography, regression models did not reveal effects of group or body stature. CONCLUSIONS: Our results support the existence of a population-specific bias in motor function patterns in young healthy adults. This needs to be considered when motor function is assessed and used for clinical decisions, especially for personalized predictive and preventive medical purposes. The bias affected only the performance of specific items and parameters and is not fully explained by population-specific ethnic differences in body stature. It may be partially explained as cultural bias related to motor habits. Observed effects were small but are expected to be larger in a non-controlled cross-cultural application of motion assessment technologies with relevance for related algorithms that are being developed and used for data processing. In sum, the interpretation of individual data should be related to appropriate population-specific or even better personalized normative values to yield its full potential and avoid misinterpretation

Proposal for post hoc quality control in instrumented motion analysis using markerless motion capture: development and usability study

BACKGROUND: Instrumented assessment of motor symptoms has emerged as a promising extension to the clinical assessment of several movement disorders. The use of mobile and inexpensive technologies such as some markerless motion capture technologies is especially promising for large-scale application but has not transitioned into clinical routine to date. A crucial step on this path is to implement standardized, clinically applicable tools that identify and control for quality concerns. OBJECTIVE: The main goal of this study comprises the development of a systematic quality control (QC) procedure for data collected with markerless motion capture technology and its experimental implementation to identify specific quality concerns and thereby rate the usability of recordings. METHODS: We developed a post hoc QC pipeline that was evaluated using a large set of short motor task recordings of healthy controls (2010 recordings from 162 subjects) and people with multiple sclerosis (2682 recordings from 187 subjects). For each of these recordings, 2 raters independently applied the pipeline. They provided overall usability decisions and identified technical and performance-related quality concerns, which yielded respective proportions of their occurrence as a main result. RESULTS: The approach developed here has proven user-friendly and applicable on a large scale. Raters' decisions on recording usability were concordant in 71.5%-92.3% of cases, depending on the motor task. Furthermore, 39.6%-85.1% of recordings were concordantly rated as being of satisfactory quality whereas in 5.0%-26.3%, both raters agreed to discard the recording. CONCLUSIONS: We present a QC pipeline that seems feasible and useful for instant quality screening in the clinical setting. Results confirm the need of QC despite using standard test setups, testing protocols, and operator training for the employed system and by extension, for other task-based motor assessment technologies. Results of the QC process can be used to clean existing data sets, optimize quality assurance measures, as well as foster the development of automated QC approaches and therefore improve the overall reliability of kinematic data sets

Digital motor biomarkers of cerebellar ataxia using an RGB-Depth camera-based motion analysis system

This study aimed to identify quantitative biomarkers of motor function for cerebellar ataxia by evaluating gait and postural control using an RGB-depth camera-based motion analysis system. In 28 patients with degenerative cerebellar ataxia and 33 age- and sex-matched healthy controls, motor tasks (short-distance walk, closed feet stance, and stepping in place) were selected from a previously reported protocol, and scanned using Kinect V2 and customized software. The Clinical Assessment Scale for the Assessment and Rating of Ataxia (SARA) was also evaluated. Compared with the normal control group, the cerebellar ataxia group had slower gait speed and shorter step lengths, increased step width, and mediolateral trunk sway in the walk test (all P < 0.001). Lateral sway increased in the stance test in the ataxia group (P < 0.001). When stepping in place, the ataxia group showed higher arrhythmicity of stepping and increased stance time (P < 0.001). In the correlation analyses, the ataxia group showed a positive correlation between the total SARA score and arrhythmicity of stepping in place (r = 0.587, P = 0.001). SARA total score (r = 0.561, P = 0.002) and gait subscore (ρ = 0.556, P = 0.002) correlated with mediolateral truncal sway during walking. These results suggest that the RGB-depth camera-based motion analyses on mediolateral truncal sway during walking and arrhythmicity of stepping in place are useful digital motor biomarkers for the assessment of cerebellar ataxia, and could be utilized in future clinical trials