Clinical Movement Control and real-life Behavior Analysis for Assistive Systems

Abstract:

BACKGROUND AND AIM: Ataxic gait is typically characterized by an unstable, stumbling gait, increased step width, and high gait variability. The characteristic high variability is thought to result from the complex interaction between cerebellar-induced deficits in balance control and multi-joint coordination, the compensatory strategies used, and inaccurate postural adjustments to the apparent loss of balance. The interplay and relative importance of these individual factors and their development over the course of the disease are not fully understood. Clarifying their relationship during disease progression would allow both efficient neurorehabilitation and the development of disease-phase sensitive performance markers for clinical trials. Here, we aimed to investigate the role of ataxia-specific balance dysfunction in static (stance) and dynamic (gait) conditions, particularly in very early and pre-symptomatic disease stages (i.e., mutation carriers without clinical manifestation). METHODS: We assessed static and dynamic balance of subjects with degenerative cerebellar ataxia at baseline and 1-year follow-up using three body-worn inertial sensors. Stance conditions included natural stance and feet together stance with eyes opened and eyes closed. As a measure of static balance performance we used the sway path length (SPL) based on the hip sensor. Walking was performed in laboratory settings, i.e., supervised straight walking of a 60m corridor at preferred speed, and unsupervised in real life. The compound measure of spatial step variability (SPcmp), which integrates step length variability and lateral step deviation, served as a measure of ataxia-specific gait variability. RESULTS: Cross-sectional analysis of symptomatic ataxia patients (n = 44, SARA = 10.1) revealed correlations between SPL during natural stance and SPcmp during walking, with increasing effects moving from laboratory (r = 0.36, p {\textless} 0.0001) to real-life conditions (r = 0.51, p {\textless} 0.0001). For the group of pre-ataxic mutations carriers (n = 33, SARA = 0.7) we saw a strong trend for the relation of gait variability and sway in a stance task with increased complexity (i.e., feet together, eyes closed) (r = 0.25, p = 0.06). The relation was particularly evident longitudinally when 1-year changes in stance sway and gait variability were correlated (r = 0.44, p = 0.01). CONCLUSIONS: We were able to identify specific influences of the static balance mechanism on gait in pre-symptomatic mutation carriers, suggesting that alterations in balance control mechanisms already play a verifiable role in pre-symptomatic and very early disease stages, whereas cerebellar-induced deficits in balance control and multi-joint coordination and compensatory strategies such as slowing down may have a greater influence in later disease stages. This highlights the importance of static stance testing and related balance exercises in rehabilitation, particularly in pre-symptomatic and early disease stages.

Authors: Bohn, Kristina; Seemann, Jens; Synofzik, Matthis Ilg, Winfried

Research Areas: Clinical Movement Control and real-life Behavior Analysis for Assistive Systems

Type of Publication: In Collection

Abstract:

Upper-limb activities of daily living like eating and drinking are crucial for self-determination and autonomy and, thus, quality of life. Patients with neurodegenerative diseases such as Parkinson’s disease, multiple sclerosis or cerebellar ataxia are often severely impaired in performing these activities of daily living. While these patients are still able to plan motor actions, and their muscle strength is rarely impaired, tremor or overshooting movements disturb the intended movements. This occurs progressively in the course of disease in a way that inde- pendent eating and drinking becomes increasingly difficult. The goal of this research project is to develop a non-invasive assistive device suppressing pathological movement components while allowing intended movement. The newly designed hardware will be controlled by a combination of computational methods to detect user intention, detect pathological movement components within intended movements, and predict the required correction forces for several upper-limb activities of daily living. In this manuscript, we will describe concepts of control hard- and software as well as first implementation and experiments with the individual components we plan to integrate in the future.

Authors: Ilg, Winfried; Wochner, Isabell Charaja, Jhon Paul Feliciano Hofmann, Veronika Strenge, Ole Adam, Melanie Lendway, Regine Kerner, Jan Vashisht, Bhavya Deep Ackermann, Marko Bunjes, Friedemann Schneider, Urs Giese, Martin A.; Bulling, Andreas Schmitt, Syn Maufroy, Christophe Haeufle, Daniel Florian Benedict

Research Areas: Clinical Movement Control and real-life Behavior Analysis for Assistive Systems

Type of Publication: In Proceedings

Book title: Proc. International Consortium for Rehabilitation Robotics (ICORR)

Pages: 1-6

Abstract:

Effective trial-planning in Spastic ataxias (SPAX) is impeded by the absence of validated outcome measures for detecting longitudinal changes. Digital outcome measures show promise, demonstrating sensitivity to disease severity changes in ataxia and strong correlations with clinical scales. The objective of this study was to develop a smartphone application for SPAX (SPAX-app) to obtain valid digital outcome measures for use in clinical trials. The app contains four tasks assessing gait, standing balance (stance), and finger and hand movements. We carried out a validation study in 22 SPAX patients and 10 controls. Subjects performed the tasks three times during one visit. In parallel, we performed Ambulatory Parkinson's Disease Monitoring (APDM) sensor recordings, Q-motor upper limb assessment, and the Scale for the Assessment and Rating of Ataxia (SARA). Significant correlations were found between the SPAX-app and APDM or Q-motor for step time (r = 0.91), all measures of stance (r = 0.51-0.87) and duration of hand alternation (r = 0.64). No significant correlations were found for variability measures (e.g. standard deviation of step time). All tasks of the SPAX-app, except for stance, can discriminate SPAX from controls and show moderate to high test-retest reliability (ICC 0.67-0.97). Significant correlations were found between SARA and step time (r = 0.70), inter-onset interval in finger tapping (r = 0.57), and duration of hand alternation (r = 0.65). The stance task did not show significant correlations with SARA. With the SPAX-app, we present a set of digital outcome measures for potential use in clinical trials. Longitudinal studies are needed to evaluate whether these measures can track disease progression.

Authors: Willemse, Ilse Mellone, Sabato Tacconi, Carlo Ilg, Winfried; Schüle, Rebecca Synofzik, Matthis Nonnekes, Jorik Warrenburg, Bart

Research Areas: Clinical Movement Control and real-life Behavior Analysis for Assistive Systems

Type of Publication: Article

Journal: The Cerebellum

Volume: 24

Year: 2025

Month: 03

Abstract:

OBJECTIVES: With disease-modifying drugs for degenerative ataxias on the horizon, ecologically valid measures of motor performance that can detect patient-relevant changes in short, trial-like time frames are highly warranted. In this 2-year longitudinal study, we aimed to unravel and evaluate measures of ataxic gait which are sensitive to longitudinal changes in patients{\textquoteright} real life by using wearable sensors. METHODS: We assessed longitudinal gait changes of 26 participants with degenerative cerebellar disease (SARA:9.4{\textpm}4.1) at baseline, 1-year and 2-year follow-up assessment using 3 body-worn inertial sensors in two conditions: (1) laboratory-based walking (LBW); (2) real-life walking (RLW) during everyday living. In the RLW condition, a context-sensitive analysis was performed by selecting comparable walking bouts according to macroscopic gait characteristics, namely bout length and number of turns within a two-minute time interval. Movement analysis focussed on measures of spatio-temporal variability, in particular stride length variability, lateral step deviation, and a compound measure of spatial variability (SPCmp). RESULTS: Gait variability measures showed high test-retest reliability in both walking conditions (ICC \> 0.82). Cross-sectional analyses revealed high correlations of gait measures with ataxia severity (SARA, effect size ρ >= 0.75); and in particular with patients{\textquoteright} subjective balance confidence (ABC score, ρ>=0.71), here achieving higher effect sizes for real-life than lab-based gait measures (e.g. SPCmp: RLW ρ=0.81 vs LBW ρ=0.71). While the clinician-reported outcome SARA showed longitudinal changes only after two years, the gait measure SPCmp revealed changes already after one year with high effect size (rprb=0.80). In the subgroup with spinocerebellar ataxia type 1, 2 or 3 (SCA1/2/3), the effect size was even higher (rprb=0.86). Based on these effect sizes, sample size estimation for the gait measure SPCmp showed a required cohort size of n=42 participants (n=38 for SCA1/2/3 subgroup) for detecting a 50\% reduction of natural progression after one year by a hypothetical intervention, compared to n=254 for the SARA. CONCLUSIONS: Gait variability measures revealed high reliability and sensitivity to longitudinal change in both laboratory-based constrained walking as well as in real-life walking. Due to their ecological validity and larger effect sizes, characteristics of real-life gait recordings are promising motor performance measures as outcomes for future treatment trials.Competing Interest StatementDr Ilg received consultancy honoraria by Ionis Pharmaceuticals, unrelated to the present work. Mr Seemann reports no disclosures. Mrs Beyme reports no disclosures. Mrs John reports no disclosures. Mr Harmuth reports no disclosures. Prof Giese reports no disclosures. Prof Schoels served as advisor for Alexion, Novartis and Vico. He participates as a principal investigator in clinical studies sponsored by Vigil Neuroscience (VGL101-01.001; VGL101-01.002), Vico Therapeutics (VO659-CT01), PTC Therapeutics (PTC743-NEU-003-FA) and Stealth BioTherapeutics (SPIMD-301), all unrelated to the present work. Prof Timmann reports no disclosures. Prof Synofzik has received consultancy honoraria from Ionis, UCB, Prevail, Orphazyme, Biogen, Servier, Reata, GenOrph, AviadoBio, Biohaven, Zevra, Lilly, and Solaxa, all unrelated to the present manuscript. Funding StatementThis work was supported by the International Max Planck Research School for Intelligent Systems (IMPRS-IS) (to J.S.) and the Else Kroener-Fresenius-Stiftung Medical Scientist programme ClinbrAIn (to W.I. and M.G.). as well as the Else Kroener-Fresenius Stiftung Clinician Scientist program PRECISE.net (to M.S.). In addition, this work was supported by the European Union, project European Rare Disease Research Alliance (ERDERA, $\#$ 101156595) (to M.S.).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Ethics committee/IRB of University Tuebingen, Germany gave ethical approval for this workI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.YesData will be made available upon reasonable request. The authors confirm that the data supporting the findings of this study are available within the article and its Supplementary material. Raw data regarding human participants (e.g. clinical data) are not shared freely to protect the privacy of the human participants involved in this study; no consent for open sharing has been obtained.

Authors: Seemann, Jens; Beyme, Theresa John, Natalie Harmuth, Florian Giese, Martin A.; Schöls, Ludger Timmann, Dagmar Synofzik, Matthis Ilg, Winfried

Research Areas: Clinical Movement Control and real-life Behavior Analysis for Assistive Systems

Type of Publication: Article