Rüdiger Rupp

Proceedings of the first workshop on peripheral machine interfaces: Going beyond traditional surface electromyography

One of the hottest topics in rehabilitation robotics is that of proper control of prosthetic devices. Despite decades of research, the state of the art is dramatically behind the expectations. To shed light on this issue, in June, 2013 the first international workshop on Present and future of non-invasive peripheral nervous system (PNS)–Machine Interfaces (MI; PMI) was convened, hosted by the International Conference on Rehabilitation Robotics. The keyword PMI has been selected to denote human–machine interfaces targeted at the limb-deficient, mainly upper-limb amputees, dealing with signals gathered from the PNS in a non-invasive way, that is, from the surface of the residuum. The workshop was intended to provide an overview of the state of the art and future perspectives of such interfaces; this paper represents is a collection of opinions expressed by each and every researcher/group involved in it.

Identifying Homogeneous Subgroups in Neurological Disorders Unbiased Recursive Partitioning in Cervical Complete Spinal Cord Injury

Background. The reliable stratification of homogeneous subgroups and the prediction of future clinical outcomes within heterogeneous neurological disorders is a particularly challenging task. Nonetheless, it is essential for the implementation of targeted care and effective therapeutic interventions. Objective. This study was designed to assess the value of a recently developed regression tool from the family of unbiased recursive partitioning methods in comparison to established statistical approaches (eg, linear and logistic regression) for predicting clinical endpoints and for prospective patients’ stratification for clinical trials. Methods. A retrospective, longitudinal analysis of prospectively collected neurological data from the European Multicenter study about Spinal Cord Injury (EMSCI) network was undertaken on C4-C6 cervical sensorimotor complete subjects. Predictors were based on a broad set of early (<2 weeks) clinical assessments. Endpoints were based on later clinical examinations of upper extremity motor scores and recovery of motor levels, at 6 and 12 months, respectively. Prediction accuracy for each statistical analysis was quantified by resampling techniques. Results. For all settings, overlapping confidence intervals indicated similar prediction accuracy of unbiased recursive partitioning to established statistical approaches. In addition, unbiased recursive partitioning provided a direct way of identification of more homogeneous subgroups. The partitioning is carried out in a data-driven manner, independently from a priori decisions or predefined thresholds. Conclusion. Unbiased recursive partitioning techniques may improve prediction of future clinical endpoints and the planning of future SCI clinical trials by providing easily implementable, data-driven rationales for early patient stratification based on simple decision rules and clinical read-outs.

Prediction of Bladder Outcomes after Traumatic Spinal Cord Injury: A Longitudinal Cohort Study.

Background Neurogenic bladder dysfunction represents one of the most common and devastating sequelae of traumatic spinal cord injury (SCI). As early prediction of bladder outcomes is essential to counsel patients and to plan neurourological management, we aimed to develop and validate a model to predict urinary continence and complete bladder emptying 1 y after traumatic SCI. Methods and Findings Using multivariate logistic regression analysis from the data of 1,250 patients with traumatic SCI included in the European Multicenter Spinal Cord Injury study, we developed two prediction models of urinary continence and complete bladder emptying 1 y after traumatic SCI and performed an external validation in 111 patients. As predictors, we evaluated age, gender, and all variables of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and of the Spinal Cord Independence Measure (SCIM). Urinary continence and complete bladder emptying 1 y after SCI were assessed through item 6 of SCIM. The full model relies on lower extremity motor score (LEMS), light-touch sensation in the S3 dermatome of ISNCSI, and SCIM subscale respiration and sphincter management: the area under the receiver operating characteristics curve (aROC) was 0.936 (95% confidence interval [CI]: 0.922–0.951). The simplified model is based on LEMS only: the aROC was 0.912 (95% CI: 0.895–0.930). External validation of the full and simplified models confirmed the excellent predictive power: the aROCs were 0.965 (95% CI: 0.934–0.996) and 0.972 (95% CI 0.943–0.999), respectively. This study is limited by the substantial number of patients with a missing 1-y outcome and by differences between derivation and validation cohort. Conclusions Our study provides two simple and reliable models to predict urinary continence and complete bladder emptying 1 y after traumatic SCI. Early prediction of bladder function might optimize counselling and patient-tailored rehabilitative interventions and improve patient stratification in future clinical trials.

Brain–Computer Interfaces and Assistive Technology

Assistive technology (AT) supports individuals with motor, sensory, or cognitive disabilities in performing functions that might otherwise be difficult or impossible for them. In particular, individuals with severe motor impairments have a high need for assistive devices supporting access to information technologies, improving mobility, and restoring manipulation abilities. Established human–machine interfaces are dependent on the presence of a sufficient number of residual motor functions. Brain–Computer Interfaces (BCIs) are technical systems that provide a direct connection between the human brain and a computer and can serve as a user interface for the control of assistive devices. Historically, non-invasive BCIs were intended to provide basic communication skills to patients with locked-in syndrome. Since then BCI technology has evolved tremendously and nowadays BCIs are used as an alternative or additional control channel for many other applications. Among them are extended communication applications like accessing the internet or Brain Painting. Wheelchairs and telepresence robots can be navigated with the help of BCIs, and motor-imagery-based BCIs in particular are an attractive perspective for an intuitive neuroprosthesis control. The recent development of the hybrid BCI combining a BCI with other preserved control signals fits well in the user-centered design concept, since BCIs can be seamlessly integrated in traditional AT. Although current non-invasive BCIs are at the stage of entering people’s homes, they still cannot be operated by end-users alone. More home-based studies are needed to further improve the usability and reliability of BCIs and to better address specific needs and requirements of end-users.

Toward Inclusive Trial Protocols in Heterogeneous Neurological Disorders Prediction-Based Stratification of Participants With Incomplete Cervical Spinal Cord Injury

Background. Several novel drug- and cell-based potential therapies for spinal cord injury (SCI) have either been applied or will be considered for future clinical trials. Limitations on the number of eligible patients require trials be undertaken in a highly efficient and effective manner. However, this is particularly challenging when people living with incomplete SCI (iSCI) represent a very heterogeneous population in terms of recovery patterns and can improve spontaneously over the first year after injury. Objective. The current study addresses 2 requirements for designing SCI trials: first, enrollment of as many eligible participants as possible; second, refined stratification of participants into homogeneous cohorts from a heterogeneous iSCI population. Methods. This is a retrospective, longitudinal analysis of prospectively collected SCI data from the European Multicenter study about Spinal Cord Injury (EMSCI). We applied conditional inference trees to provide a prediction-based stratification algorithm that could be used to generate decision rules for the appropriate inclusion of iSCI participants to a trial. Results. Based on baseline clinical assessments and a defined subsequent clinical endpoint, conditional inference trees partitioned iSCI participants into more homogeneous groups with regard to the illustrative endpoint, upper extremity motor score. Assuming a continuous endpoint, the conditional inference tree was validated both internally as well as externally, providing stable and generalizable results. Conclusion. The application of conditional inference trees is feasible for iSCI participants and provides easily implementable, prediction-based decision rules for inclusion and stratification. This algorithm could be utilized to model various trial endpoints and outcome thresholds.

MotionTherapy@Home - A robotic device for automated locomotion therapy at home

Lesions of the central nervous system often lead to walking impairments. Primary rehabilitation aims at the improvement of the gait capacity by application of task oriented training regimes utilizing the inherent capability of neural networks for reorganization. However, a sufficient training intensity for enhancement of this neuroplasticity can only be achieved during the inpatient phase, which - due to economical restrictions - is getting shorter and shorter. In the clinical environment complex and expensive robotic devices have been introduced to maintain the duration and the intensity of the training, but up to now only a few exist for continuation of an automated locomotion training at home. Hence this project aims at the development of a compact, modular, individually adaptable motor driven orthosis for home based gait training. In contrast to ergometer or continuous passive motion devices the novel “MoreGait” system is capable of generating the proprioceptive and sensory stimuli in particular the gait-phase dependent loading of the foot soles, which have been identified recently also in humans as key afferent inputs of the spinal gait pattern generator. Artificial pneumatic muscles with excellent weight-to-force ratio have been integrated as actuators for ankle joint and combined hip-knee movements. Their inherent low stiffness efficiently supports the safety concept of the device, which is intended to be operated by the handicapped users completely on their own including transfers from the wheelchair. A nonlinear observer based controller has been implemented for the knee joint and a model based feedback controller for the ankle to compensate the highly nonlinear behavior of the mechanical system. For safety reasons a semi-recumbent position of the user has been foreseen, in which a foot loading cannot be achieved by the users own body weight. Therefore the Stimulative Shoe has been developed on the basis of pneumatically actuated medio-lateral bars mimicking the physiological foot loading pattern. The users operate the device via an intuitive user interface and receive feedback about their training activities through a graphical representation of model-based derived joint torques.

First-in-Man Intrathecal Application of Neurite Growth-Promoting Anti-Nogo-A Antibodies in Acute Spinal Cord Injury:

Background. Neutralization of central nervous system neurite growth inhibitory factors, for example, Nogo-A, is a promising approach to improving recovery following spinal cord injury (SCI). In animal SCI models, intrathecal delivery of anti-Nogo-A antibodies promoted regenerative neurite growth and functional recovery. Objective. This first-in-man study assessed the feasibility, safety, tolerability, pharmacokinetics, and preliminary efficacy of the human anti-Nogo-A antibody ATI355 following intrathecal administration in patients with acute, complete traumatic paraplegia and tetraplegia. Methods. Patients (N = 52) started treatment 4 to 60 days postinjury. Four consecutive dose-escalation cohorts received 5 to 30 mg/2.5 mL/day continuous intrathecal ATI355 infusion over 24 hours to 28 days. Following pharmacokinetic evaluation, 2 further cohorts received a bolus regimen (6 intrathecal injections of 22.5 and 45 mg/3 mL, respectively, over 4 weeks). Results. ATI355 was well tolerated up to 1-year follow-up. All patients experienced ≥1 adverse events (AEs). The 581 reported AEs were mostly mild and to be expected following acute SCI. Fifteen patients reported 16 serious AEs, none related to ATI355; one bacterial meningitis case was considered related to intrathecal administration. ATI355 serum levels showed dose-dependency, and intersubject cerebrospinal fluid levels were highly variable after infusion and bolus injection. In 1 paraplegic patient, motor scores improved by 8 points. In tetraplegic patients, mean total motor scores increased, with 3/19 gaining >10 points, and 1/19 27 points at Week 48. Conversion from complete to incomplete SCI occurred in 7/19 patients with tetraplegia. Conclusions. ATI335 was well tolerated in humans; efficacy trials using intrathecal antibody administration may be considered in acute SCI.

Feasibility of visual instrumented movement feedback therapy in individuals with motor incomplete spinal cord injury walking on a treadmill

Background: Incomplete spinal cord injury (iSCI) leads to motor and sensory deficits. Even in ambulatory persons with good motor function an impaired proprioception may result in an insecure gait. Limited internal afferent feedback (FB) can be compensated by provision of external FB by therapists or technical systems. Progress in computational power of motion analysis systems allows for implementation of instrumented real-time FB. The aim of this study was to test if individuals with iSCI can normalize their gait kinematics during FB and more importantly maintain an improvement after therapy. Methods: Individuals with chronic iSCI had to complete 6 days (1 day per week) of treadmill-based FB training with a 2 weeks pause after 3 days of training. Each day consists of an initial gait analysis followed by 2 blocks with FB/no-FB. During FB the deviation of the mean knee angle during swing from a speed matched reference (norm distance, ND) is visualized as a number. The task consists of lowering the ND, which was updated after every stride. Prior to the tests in patients the in-house developed FB implementation was tested in healthy subjects with an artificial movement task. Results: Four of five study participants benefited from FB in the short and medium term. Decrease of mean ND was highest during the first 3 sessions (from 3.93 ± 1.54 to 2.18 ± 1.04). After the pause mean ND stayed in the same range than before. In the last 3 sessions the mean ND decreased slower (2.40 ± 1.18 to 2.20 ± 0.90). Direct influences of FB ranged from 60 to 15% of reduction in mean ND compared to initial gait analysis and from 20 to 1% compared to no-FB sessions. Conclusions: Instrumented kinematic real-time FB may serve as an effective adjunct to established gait therapies in normalizing the gait pattern after incomplete spinal cord injury. Further studies with larger patient groups need to prove long term learning and the successful transfer of newly acquired skills to activities of daily living.

Trainer in a pocket - proof-of-concept of mobile, real-time, foot kinematics feedback for gait pattern normalization in individuals after stroke, incomplete spinal cord injury and elderly patients

BackgroundWalking disabilities negatively affect inclusion in society and quality of life and increase the risk for secondary complications. It has been shown that external feedback applied by therapists and/or robotic training devices enables individuals with gait abnormalities to consciously normalize their gait pattern. However, little is known about the effects of a technically-assisted over ground feedback therapy. The aim of this study was to assess whether automatic real-time feedback provided by a shoe-mounted inertial-sensor-based gait therapy system is feasible in individuals with gait impairments after incomplete spinal cord injury (iSCI), stroke and in the elderly.MethodsIn a non-controlled proof-of-concept study, feedback by tablet computer-generated verbalized instructions was given to individuals with iSCI, stroke and old age for normalization of an individually selected gait parameter (stride length, stance or swing duration, or foot-to-ground angle). The training phase consisted of 3 consecutive visits. Four weeks post training a follow-up visit was performed. Visits started with an initial gait analysis (iGA) without feedback, followed by 5 feedback training sessions of 2–3xa0min and a gait analysis at the end. A universal evaluation and FB scheme based on equidistant levels of deviations from the mean normal value (1 levelu2009=u20091 standard deviation (SD) of the physiological reference for the feedback parameter) was used for assessment of gait quality as well as for automated adaptation of training difficulty. Overall changes in level over iGAs were detected using a Friedman’s Test. Post-hoc testing was achieved with paired Wilcoxon Tests. The users’ satisfaction was assessed by a customized questionnaire.ResultsFifteen individuals with iSCI, 11 after stroke and 15 elderly completed the training. The average level at iGA significantly decreased over the visits in all groups (Friedman’s test, pu2009<u20090.0001), with the biggest decrease between the first and second training visit (4.78u2009±u20092.84 to 3.02u2009±u20092.43, pu2009<u20090.0001, paired Wilcoxon test). Overall, users rated the system’s usability and its therapeutic effect as positive.ConclusionsMobile, real-time, verbalized feedback is feasible and results in a normalization of the feedback gait parameter. The results form a first basis for using real-time feedback in task-specific motor rehabilitation programs.Trial registrationDRKS00011853, retrospectively registered on 2017/03/23.

Evaluation of electrical impedance tomography for determination of urinary bladder volume: comparison with standard ultrasound methods in healthy volunteers

BackgroundContinuous non-invasive urinary bladder volume measurement (cystovolumetry) would allow better management of urinary tract disease. Electrical impedance tomography (EIT) represents a promising method to overcome the limitations of non-continuous ultrasound measurements. The aim of this study was to compare the measurement accuracy of EIT to standard ultrasound in healthy volunteers.MethodsFor EIT of the bladder a commercial device (Goe MF II) was used with 4 different configurations of 16 standard ECG electrodes attached to the lower abdomen of healthy participants. To estimate maximum bladder capacity (BCmax) and residual urine (RU) two ultrasound methods (US-Ellipsoid and US-Lu2009×u2009Wu2009×u2009H) and a bedside bladder scanner (BS), were performed at the point of urgency and after voiding. For volume reference, BCmax and RU were validated by urine collection in a weight measuring pitcher. The global impedance method was used offline to estimate BCmax and RU from EIT.ResultsThe mean error of US-Ellipsoid (37u2009±u200917%) and US-Lu2009×u2009Wu2009×u2009H (36u2009±u200915%) and EIT (32u2009±u200918%) showed no significant differences in the estimation of BCmax (mean 743u2009±u2009200xa0ml) normalized to pitcher volumetry. BS showed significantly worse accuracy (55u2009±u20099%). Volumetry of RU (mean 152.1u2009±u200964xa0ml) revealed comparable higher errors for both EIT (72u2009±u200958%) and BS (63u2009±u200924%) compared to US-Ellipsoid (54u2009±u200925%). In case of RU, EIT accuracy is dependent on electrode configuration, as the Stripes (41u2009±u200925%) and Matrix (38u2009±u200927%) configurations revealed significantly superior accuracy to the 1u2009×u200916 (116u2009±u200962%) configuration.ConclusionsEIT-cystovolumetry compares well with ultrasound techniques. For estimation of RU, the selection of the EIT electrode configuration is important. Also, the development of an algorithm should consider the impact of movement artefacts. Finally, the accuracy of non-invasive ultrasound accepted as gold standard of cystovolumetry should be reconsidered.