Assessing walking ability using a robotic gait trainer: opportunities and limitations of assist-as-needed control in spinal cord injury.

BACKGROUND: Walking impairments are a common consequence of neurological disorders and are assessed with clinical scores that suffer from several limitations. Robot-assisted locomotor training is becoming an established clinical practice. Besides training, these devices could be used for assessing walking ability in a controlled environment. Here, we propose an adaptive assist-as-needed (AAN) control for a treadmill-based robotic exoskeleton, the Lokomat, that reduces the support of the device (body weight support and impedance of the robotic joints) based on the ability of the patient to follow a gait pattern displayed on screen. We hypothesize that the converged values of robotic support provide valid and reliable information about individuals' walking ability. METHODS: Fifteen participants with spinal cord injury and twelve controls used the AAN software in the Lokomat twice within a week and were assessed using clinical scores (10MWT, TUG). We used a regression method to identify the robotic measure that could provide the most relevant information about walking ability and determined the test-retest reliability. We also checked whether this result could be extrapolated to non-ambulatory and to unimpaired subjects. RESULTS: The AAN controller could be used in patients with different injury severity levels. A linear model based on one variable (robotic knee stiffness at terminal swing) could explain 74% of the variance in the 10MWT and 61% in the TUG in ambulatory patients and showed good relative reliability but poor absolute reliability. Adding the variable 'maximum hip flexor torque' to the model increased the explained variance above 85%. This did not extend to non-ambulatory nor to able-bodied individuals, where variables related to stance phase and to push-off phase seem more relevant. CONCLUSIONS: The novel AAN software for the Lokomat can be used to quantify the support required by a patient while performing robotic gait training. The adaptive software might enable more challenging training conditions tuned to the ability of the individuals. While the current implementation is not ready for assessment in clinical practice, we could demonstrate that this approach is safe, and it could be integrated as assist-as-needed training, rather than as assessment. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02425332.

Feasibility of an Intelligent Algorithm Based on an Assist-as-Needed Controller for a Robot-Aided Gait Trainer (Lokomat) in Neurological Disorders: A Longitudinal Pilot Study.

Most robotic gait assisted devices are designed to provide constant assistance during the training without taking into account each patient's functional ability. The Lokomat offers an assist-as-needed control via the integrated exercise "Adaptive Gait Support" (AGS), which adapts the robotic support based on the patient's abilities. The aims of this study were to examine the feasibility and characteristics of the AGS during long-term application. Ten patients suffering from neurological diseases underwent an 8-week Lokomat training with the AGS. They additionally performed conventional walking tests and a robotic force measurement. The difference between robotic support during adaptive and conventional training and the relationship between the robotic assessment and the conventional walking and force tests were examined. The results show that AGS is feasible during long-term application in a heterogeneous population. The support during AGS training in most of the gait phases was significantly lower than during conventional Lokomat training. A relationship between the robotic support level determined by the AGS and conventional walking tests was revealed. Moreover, combining the isometric force data and AGS data could divide patients into clusters, based on their ability to generate high forces and their level of motor control. AGS shows a high potential in assessing patients' walking ability, as well as in providing challenging training, e.g., by automatically adjusting the robotic support throughout the whole gait cycle and enabling training at lower robotic support.

Rasch validation and refinement of the Lymphedema Life Impact Scale version 2 in an Italian cohort with secondary lymphedema.

PURPOSE: To produce and validate an Italian version of the Lymphedema Life Impact Scale version 2 (LLISv2-It), a tool measuring the impact of lymphedema on health-related quality of life, and investigate its main psychometric characteristics. METHODS: After translation and cross-cultural adaptation of the LLISv2, we administered it to 156 subjects with secondary lymphedema (upper or lower limb), together with (depending on the limb involved) either the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) or the Lower Extremity Functional Scale (LEFS). We analyzed the performance of LLISv2-It using Classical Test Theory and Rasch methods. RESULTS: Cronbach alpha was 0.89. Item fit statistics indicated that item #12 was underfitting (Infit MnSQ = 1.56; Outfit MnSq = 1.75). Test-retest reliability of the 17-item version (without item #18, not scored, according to the original authors) and of a 16-item version (without #12 and #18-a unidimensional item set) were both excellent (ICC2.1 = 0.93; 95%). The minimum detectable change was 8.9 points. The correlation of LLISv2-It with DASH and LEFS was r = 0.81 and -0.57, respectively. CONCLUSIONS: The Italian version of the LLISv2 is reliable and valid. To make the tool more psychometrically sound, we recommend to not calculate items #12 and #18 in the total score.IMPLICATIONS FOR REHABILITATIONThe Lymphedema Life Impact Scale (LLISv2) is particularly useful as a validated condition-specific health-related quality of life measure for patients with chronic edema/lymphedema. We have validated its Italian version (LLISv2-It).We also examined the psychometric properties of the LLISv2 in individuals with secondary lymphedema of either upper or lower limb, using both classical test theory and Rasch techniques, to provide insights for further refinement of the questionnaire.Based on our results, we recommend not to count item #12 in the total score (besides #18, as already suggested by the original authors). Moreover, we determined that the minimum detectable change of the LLISv2 was 9 points. This information is helpful in clinical practice to understand if the change in score is not due to chance (measurement error).Although further research is warranted, the present validation study of the LLISv2 increases the confidence in the metric quality and clinical utility of the scale to assess lymphedema-specific health-related quality of life in individuals with secondary lymphedema of either upper or lower limb.

Lymphedema quality of life questionnaire (LYMQOL): cross-cultural adaptation and validation in Italian women with upper limb lymphedema after breast cancer.

PURPOSE: There is growing interest in measures that assess upper-limb lymphedema after breast cancer. Since no validated Italian version of the Lymphedema Quality of Life Questionnaire for upper limbs (LYMQOL-UL) exists, we aimed to culturally adapt and validate an Italian version (LYMQOL-UL-IT) in order to allow its use in Italian patients. MATERIALS AND METHODS: The LYMQOL-UL-IT was developed by means of forward-backward translation, review by an expert committee and a test of the pre-final version to evaluate its comprehensibility. The psychometric testing included reliability by internal consistency (Cronbach's alpha) and test-retest reliability (intraclass correlation coefficient, ICC(2.1)), measurement error by calculating the minimum detectable change (MDC95), construct validity by confirmatory factor analysis, and evaluation of a priori hypotheses about the correlations between the four LYMQOL-UL domains, single items of the LYMQOL-UL, and measures of health-related quality of life and pain intensity (Spearman's rank correlation coefficient). RESULTS: The consensus-based version of LYMQOL-UL-IT was administered to 139 patients with upper-limb stable secondary iatrogenic lymphedema after breast cancer. The adapted questionnaire was well accepted as it was completed in less than 10 min, without missing answers or comprehension problems. Internal consistency was acceptable (α = 0.92-0.95). Test-retest reliability was good-to-excellent (ICC(2.1) = 0.73-0.96). The MDC95 for the four domains of the questionnaire was as follows: 0.64 scale points for Function, 0.40 for Appearance, 0.53 for Symptoms, and 0.81 for Mood. Factor analysis confirmed a 4-dimensional structure as originally conceived and the a priori hypotheses were met. CONCLUSION: The LYMQOL-UL-IT is reliable, sensitive to change and valid in patients with upper-limb stable secondary iatrogenic lymphedema after breast cancer. It can be used for clinical and research purposes.Implications for rehabilitationLymphedema is a frequently unnoticed clinical condition that not only impacts physical functioning but often restricts the health-related quality of life in breast cancer survivors.The Italian version of the Lymphedema Quality of Life Questionnaire for upper limbs (LYMQOL-UL-IT) is reliable, sensitive to change and valid in patients with upper-limb lymphedema after breast cancer.The LYMQOL-UL-IT tool can be recommended for clinical and research purposes.

Haptic Error Modulation Outperforms Visual Error Amplification When Learning a Modified Gait Pattern.

Robotic algorithms that augment movement errors have been proposed as promising training strategies to enhance motor learning and neurorehabilitation. However, most research effort has focused on rehabilitation of upper limbs, probably because large movement errors are especially dangerous during gait training, as they might result in stumbling and falling. Furthermore, systematic large movement errors might limit the participants' motivation during training. In this study, we investigated the effect of training with novel error modulating strategies, which guarantee a safe training environment, on motivation and learning of a modified asymmetric gait pattern. Thirty healthy young participants walked in the exoskeletal robotic system Lokomat while performing a foot target-tracking task, which required an increased hip and knee flexion in the dominant leg. Learning the asymmetric gait pattern with three different strategies was evaluated: (i) No disturbance: no robot disturbance/guidance was applied, (ii) haptic error amplification: unsafe and discouraging large errors were limited with haptic guidance, while haptic error amplification enhanced awareness of small errors relevant for learning, and (iii) visual error amplification: visually observed errors were amplified in a virtual reality environment. We also evaluated whether increasing the movement variability during training by adding randomly varying haptic disturbances on top of the other training strategies further enhances learning. We analyzed participants' motor performance and self-reported intrinsic motivation before, during and after training. We found that training with the novel haptic error amplification strategy did not hamper motor adaptation and enhanced transfer of the practiced asymmetric gait pattern to free walking. Training with visual error amplification, on the other hand, increased errors during training and hampered motor learning. Participants who trained with visual error amplification also reported a reduced perceived competence. Adding haptic disturbance increased the movement variability during training, but did not have a significant effect on motor adaptation, probably because training with haptic disturbance on top of visual and haptic error amplification decreased the participants' feelings of competence. The proposed novel haptic error modulating controller that amplifies small task-relevant errors while limiting large errors outperformed visual error augmentation and might provide a promising framework to improve robotic gait training outcomes in neurological patients.

An Adaptive and Hybrid End-Point/Joint Impedance Controller for Lower Limb Exoskeletons.

Assist-as-needed (AAN) algorithms for the control of lower extremity rehabilitation robots can promote active participation of patients during training while adapting to their individual performances and impairments. The implementation of such controllers requires the adaptation of a control parameter (often the robot impedance) based on a performance (or error) metric. The choice of how an adaptive impedance controller is formulated implies different challenges and possibilities for controlling the patient's leg movement. In this paper, we analyze the characteristics and limitations of controllers defined in two commonly used formulations: joint and end-point space, exploring especially the implementation of an AAN algorithm. We propose then, as a proof-of-concept, an AAN impedance controller that combines the strengths of working in both spaces: a hybrid joint/end-point impedance controller. This approach gives the possibility to adapt the end-point stiffness in magnitude and direction in order to provide a support that targets the kinematic deviations of the end-point with the appropriate force vector. This controller was implemented on a two-link rehabilitation robot for gait training-the Lokomat®Pro V5 (Hocoma AG, Switzerland) and tested on 5 able-bodied subjects and 1 subject with Spinal Cord Injury. Our experiments show that the hybrid controller is a feasible approach for exoskeleton devices and that it could exploit the benefits of the end-point controller in shaping a desired end-point stiffness and those of the joint controller to promote the correct angular changes in the trajectories of the joints. The adaptation algorithm is able to adapt the end-point stiffness based on the subject's performance in different gait phases, i.e., the robot can render a higher stiffness selectively in the direction and gait phases where the subjects perform with larger kinematic errors. The proposed approach can potentially be generalized to other robotic applications for rehabilitation or assistive purposes.

Robot-supported assessment of balance in standing and walking.

Clinically useful and efficient assessment of balance during standing and walking is especially challenging in patients with neurological disorders. However, rehabilitation robots could facilitate assessment procedures and improve their clinical value. We present a short overview of balance assessment in clinical practice and in posturography. Based on this overview, we evaluate the potential use of robotic tools for such assessment. The novelty and assumed main benefits of using robots for assessment are their ability to assess 'severely affected' patients by providing assistance-as-needed, as well as to provide consistent perturbations during standing and walking while measuring the patient's reactions. We provide a classification of robotic devices on three aspects relevant to their potential application for balance assessment: 1) how the device interacts with the body, 2) in what sense the device is mobile, and 3) on what surface the person stands or walks when using the device. As examples, nine types of robotic devices are described, classified and evaluated for their suitability for balance assessment. Two example cases of robotic assessments based on perturbations during walking are presented. We conclude that robotic devices are promising and can become useful and relevant tools for assessment of balance in patients with neurological disorders, both in research and in clinical use. Robotic assessment holds the promise to provide increasingly detailed assessment that allows to individually tailor rehabilitation training, which may eventually improve training effectiveness.

Robot-aided assessment of lower extremity functions: a review.

The assessment of sensorimotor functions is extremely important to understand the health status of a patient and its change over time. Assessments are necessary to plan and adjust the therapy in order to maximize the chances of individual recovery. Nowadays, however, assessments are seldom used in clinical practice due to administrative constraints or to inadequate validity, reliability and responsiveness. In clinical trials, more sensitive and reliable measurement scales could unmask changes in physiological variables that would not be visible with existing clinical scores.In the last decades robotic devices have become available for neurorehabilitation training in clinical centers. Besides training, robotic devices can overcome some of the limitations in traditional clinical assessments by providing more objective, sensitive, reliable and time-efficient measurements. However, it is necessary to understand the clinical needs to be able to develop novel robot-aided assessment methods that can be integrated in clinical practice.This paper aims at providing researchers and developers in the field of robotic neurorehabilitation with a comprehensive review of assessment methods for the lower extremities. Among the ICF domains, we included those related to lower extremities sensorimotor functions and walking; for each chapter we present and discuss existing assessments used in routine clinical practice and contrast those to state-of-the-art instrumented and robot-aided technologies. Based on the shortcomings of current assessments, on the identified clinical needs and on the opportunities offered by robotic devices, we propose future directions for research in rehabilitation robotics. The review and recommendations provided in this paper aim to guide the design of the next generation of robot-aided functional assessments, their validation and their translation to clinical practice.

Prospective study on microangiopathy in type 2 diabetic foot ulcer.

AIMS/HYPOTHESIS: We investigated the significance of microangiopathy in the development of foot ulcer, which is still disputed. METHODS: We assessed microangiopathy by histological analysis of the capillary ultrastructure using transmission electron microscopy and capillary density and arteriolar morphology in paraffin-embedded sections from the skin of type 2 diabetic patients: 30 neuroischaemic patients (Isc) revascularised with peripheral angioplasty and 30 neuropathic patients (Neu) with foot ulcer, compared with ten non-diabetic volunteers. RESULTS: In the diabetic patients, capillaries in the dermal papillary layer were fewer (-22.2%, 159 ± 43 vs 205 ± 52 mm(2) in non-diabetic volunteers, p < 0.01). They also showed detrimental remodelling, with a 2.2-fold increase in capillary basement membrane thickness (3.44 ± 1.19 vs 1.53 ± 0.34 µm in non-diabetic volunteers, p < 0.001) and a 57.7% decrease in lumen area (14.6 ± 11.1 vs 34.7 ± 27.5 µm(2), p < 0.001). No differences were observed between the diabetic Isc or Neu patients. Isc were more prone to develop arteriolar occlusion than Neu (16.8 ± 6.9% vs 6.7 ± 3.7%, respectively, p < 0.001). No patient had been amputated at 30 days and healing time was significantly longer in Isc (180 ± 120 vs 64 ± 50 days in Neu, p < 0.001). CONCLUSIONS/INTERPRETATION: Capillary microangiopathy is present in equal measure in neuroischaemic and neuropathic diabetic foot skin. The predominance of arteriolar occlusions with neuroischaemia indicated the existence of an additional 'small vessel disease' that did not affect an effective revascularisation and did not worsen the prognosis of major amputations but slowed the healing process of the neuroischaemic foot ulcer. TRIAL REGISTRATION: ClinicalTrials.gov NCT02610036.

Effects of dipeptidyl peptidase-4 (DPP-4) inhibition on angiogenesis and hypoxic injury in type 2 diabetes.

AIMS: We examined whether, in diabetic Ob/Ob mice, the dipeptidyl peptidase-4 (DPP-4) inhibitor (PKF275-055), an antihyperglycemic drug, that inhibits the biological inactivation of SDF-1 (stromal cell-derived factor-1), may increase endothelial progenitor cells (EPCs) mobilization and incorporation, which, in turn, may regenerate capillaries and reduce myocardial ischemia induced by strenuous exercise. MAIN METHODS: Half of sixteen control and Ob/Ob mice and eight Ob/Ob mice treated with PKF275-055 for four weeks underwent a forced swim protocol. Oral glucose tolerance, circulating EPCs, capillary ultrastructure and density, hypoxic areas and SDF-1 localization in myocardium were measured. KEY FINDINGS: Ob/Ob mice were glucose intolerant, had a significant low number of circulating EPCs and myocardial capillaries compared to lean controls. The DPP-4 inhibitor significantly improved their glucose tolerance, doubled the number of circulating EPCs, stimulated the formation of functional vessels and SDF-1 localization in the endothelium of myocardial capillaries and arterioles. Cardiac hypoxia after forced swim in Ob/Ob mice was significantly reduced when they were treated with the DPP-4 inhibitor. SIGNIFICANCE: DPP-4 inhibition may re-establish an adequate capillary network in the myocardium of diabetic Ob/Ob mice by the mobilization and SDF-1-mediated incorporation of EPCs and, consequently, reducing the susceptibility to myocardial ischemic injury provoked by strenuous exercise.

Increased task-uncorrelated muscle activity in childhood dystonia.

BACKGROUND: Even if movement abnormalities in dystonia are obvious on observation-based examinations, objective measures to characterize dystonia and to gain insights into its pathophysiology are still strongly needed. We hypothesize that motor abnormalities in childhood dystonia are partially due to the inability to suppress involuntary variable muscle activity irrelevant to the achievement of the desired motor task, resulting in the superposition of unwanted motion components on the desired movement. However, it is difficult to separate and quantify appropriate and inappropriate motor signals combined in the same muscle, especially during movement. METHODS: We devise an innovative and practical method to objectively measure movement abnormalities during the performance of a continuous figure-eight writing task in 7 children with dystonia and 9 age-matched healthy controls. During the execution of a continuous writing task, muscle contractions should occur at frequencies that match the frequencies of the writing outcome. We compare the power spectra of kinematic trajectories and electromyographic signals of 8 upper limb muscles to separate muscle activity with the same frequency content of the figure-eight movement (task-correlated) from activity occurring at frequencies extraneous to the task (task-uncorrelated). RESULTS: Children with dystonia present a greater magnitude of task-uncorrelated muscle components. The motor performance achieved by children with dystonia is characterized by an overall lower quality, with high spatial and temporal variability and an altered trade-off between speed and accuracy. CONCLUSIONS: Findings are consistent with the hypothesis that, in childhood dystonia, the ability to appropriately suppress variable and uncorrelated elements of movement is impaired. Here we present a proof-of-concept of a promising tool to characterize the phenomenology of movement disorders and to inform the design of neurorehabilitation therapies.

Reliability, validity and responsiveness of the cross-culturally adapted Italian version of the core outcome measures index (COMI) for the neck.

PURPOSE: Evaluation of the psychometric properties of a cross-culturally adapted questionnaire, the Core Outcome Measurement Index for neck pain (COMI-neck). METHODS: The COMI-neck was cross-culturally adapted for the Italian language using established procedures. The following psychometric properties of the instrument were then assessed in patients with chronic neck pain undergoing rehabilitation: test-retest reliability (intraclass correlation coefficient, ICC); construct validity by comparing COMI-neck with the Neck Pain and Disability Scale, a numerical pain rating scale, and the EuroQol-Five Dimension (Pearson's correlations); and responsiveness by means of Standardized Response Mean (SRM), unpaired t tests, and Receiver Operating Characteristics (ROC) curves. RESULTS: The questionnaire was completed by 103 subjects. The COMI-neck summary score displayed no relevant floor or ceiling effects. Test-retest reliability was excellent (ICC = 0.87). With one exception (symptom-specific well-being), the individual COMI items and the COMI summary score correlated to the expected extent with the scores of the reference questionnaires (r = 0.40-0.80). The mean change scores for the Italian COMI-neck differed significantly between patients with a good global outcome and those with a poor outcome (p = 0.002); SRM for the good outcome group was 1.23, and for the poor outcome group 0.40. ROC analysis revealed an area under the curve of 0.73 (95% CI: 0.62-0.85). CONCLUSIONS: This study provides evidence that the Italian version of the COMI-neck is a valid and responsive questionnaire in the population of patients examined. Its use is recommended for clinical and research purposes.