Economic evaluation of robot-assisted training versus an enhanced upper limb therapy programme or usual care for patients with moderate or severe upper limb functional limitation due to stroke: results from the RATULS randomised controlled trial.

OBJECTIVE: To determine whether robot-assisted training is cost-effective compared with an enhanced upper limb therapy (EULT) programme or usual care. DESIGN: Economic evaluation within a randomised controlled trial. SETTING: Four National Health Service (NHS) centres in the UK: Queen's Hospital, Barking, Havering and Redbridge University Hospitals NHS Trust; Northwick Park Hospital, London Northwest Healthcare NHS Trust; Queen Elizabeth University Hospital, NHS Greater Glasgow and Clyde; and North Tyneside General Hospital, Northumbria Healthcare NHS Foundation Trust. PARTICIPANTS: 770 participants aged 18 years or older with moderate or severe upper limb functional limitation from first-ever stroke. INTERVENTIONS: Participants randomised to one of three programmes provided over a 12-week period: robot-assisted training plus usual care; the EULT programme plus usual care or usual care. MAIN ECONOMIC OUTCOME MEASURES: Mean healthcare resource use; costs to the NHS and personal social services in 2018 pounds; utility scores based on EQ-5D-5L responses and quality-adjusted life years (QALYs). Cost-effectiveness reported as incremental cost per QALY and cost-effectiveness acceptability curves. RESULTS: At 6 months, on average usual care was the least costly option (£3785) followed by EULT (£4451) with robot-assisted training being the most costly (£5387). The mean difference in total costs between the usual care and robot-assisted training groups (£1601) was statistically significant (p<0.001). Mean QALYs were highest for the EULT group (0.23) but no evidence of a difference (p=0.995) was observed between the robot-assisted training (0.21) and usual care groups (0.21). The incremental cost per QALY at 6 months for participants randomised to EULT compared with usual care was £74 100. Cost-effectiveness acceptability curves showed that robot-assisted training was unlikely to be cost-effective and that EULT had a 19% chance of being cost-effective at the £20 000 willingness to pay (WTP) threshold. Usual care was most likely to be cost-effective at all the WTP values considered in the analysis. CONCLUSIONS: The cost-effectiveness analysis suggested that neither robot-assisted training nor EULT, as delivered in this trial, were likely to be cost-effective at any of the cost per QALY thresholds considered. TRIAL REGISTRATION NUMBER: ISRCTN69371850.

Transcranial direct current stimulation (tDCS) and robotic practice in chronic stroke: the dimension of timing.

BACKGROUND: Combining tDCS with robotic therapy is a new and promising form of neurorehabilitation after stroke, however the effectiveness of this approach is likely to be influenced by the relative timing of the brain stimulation and the therapy. OBJECTIVE: To measure the kinematic and neurophysiological effects of delivering tDCS before, during and after a single session of robotic motor practice (wrist extension). METHODS: We used a within-subjects repeated-measurement design in 12 chronic (>6 months) stroke survivors. Twenty minutes of anodal tDCS was delivered to the affected hemisphere before, during, or after a 20-minute session of robotic practice. Sham tDCS was also applied during motor practice. Robotic motor performance and corticomotor excitability, assessed through transcranial magnetic stimulation (TMS), were evaluated pre- and post-intervention. RESULTS: Movement speed was increased after motor training (sham tDCS) by ∼20%. Movement smoothness was improved when tDCS was delivered before motor practice (∼15%). TDCS delivered during practice did not offer any benefit, whereas it reduced speed when delivered after practice (∼10%). MEPs were present in ∼50% of patients at baseline; in these subjects motor practice increased corticomotor excitability to the trained muscle. CONCLUSIONS: In a cohort of stroke survivors, motor performance kinematics improved when tDCS was delivered prior to robotic training, but not when delivered during or after training. The temporal relationship between non-invasive brain stimulation and neurorehabilitation is important in determining the efficacy and outcome of this combined therapy.

Rehabilitation robotics.

This chapter focuses on rehabilitation robotics which can be used to augment the clinician's toolbox in order to deliver meaningful restorative therapy for an aging population, as well as on advances in orthotics to augment an individual's functional abilities beyond neurorestoration potential. The interest in rehabilitation robotics and orthotics is increasing steadily with marked growth in the last 10 years. This growth is understandable in view of the increased demand for caregivers and rehabilitation services escalating apace with the graying of the population. We provide an overview on improving function in people with a weak limb due to a neurological disorder who cannot properly control it to interact with the environment (orthotics); we then focus on tools to assist the clinician in promoting rehabilitation of an individual so that s/he can interact with the environment unassisted (rehabilitation robotics). We present a few clinical results occurring immediately poststroke as well as during the chronic phase that demonstrate superior gains for the upper extremity when employing rehabilitation robotics instead of usual care. These include the landmark VA-ROBOTICS multisite, randomized clinical study which demonstrates clinical gains for chronic stroke that go beyond usual care at no additional cost.

Robotic technology and physical medicine and rehabilitation.

In this opinion piece, I will revisit the basis for our belief that robotic manipulation is a valid approach to promote speedier and better recovery following a stroke and discuss some of the clinical evidence that led to the September 2010 guidelines for stroke care of the American Heart Association as well as the December 2010 guidelines of the Veterans Administration endorsing the use of robotic technology for the upper extremity (UE) but not for the lower extremity (LE) post-stroke rehabilitation effort.

Learning, not adaptation, characterizes stroke motor recovery: evidence from kinematic changes induced by robot-assisted therapy in trained and untrained task in the same workspace.

Both the American Heart Association and the VA/DoD endorse upper-extremity robot-mediated rehabilitation therapy for stroke care. However, we do not know yet how to optimize therapy for a particular patient's needs. Here, we explore whether we must train patients for each functional task that they must perform during their activities of daily living or alternatively capacitate patients to perform a class of tasks and have therapists assist them later in translating the observed gains into activities of daily living. The former implies that motor adaptation is a better model for motor recovery. The latter implies that motor learning (which allows for generalization) is a better model for motor recovery. We quantified trained and untrained movements performed by 158 recovering stroke patients via 13 metrics, including movement smoothness and submovements. Improvements were observed both in trained and untrained movements suggesting that generalization occurred. Our findings suggest that, as motor recovery progresses, an internal representation of the task is rebuilt by the brain in a process that better resembles motor learning than motor adaptation. Our findings highlight possible improvements for therapeutic algorithms design, suggesting sparse-activity-set training should suffice over exhaustive sets of task specific training.

Rhythmic movement in Parkinson's disease: effects of visual feedback and medication state.

Previous studies examining discrete movements of Parkinson's disease (PD) patients have found that in addition to performing movements that were slower than those of control participants, they exhibit specific deficits in movement coordination and in sensorimotor integration required to accurately guide movements. With medication, movement speed was normalized, but the coordinative aspects of movement were not. This led to the hypothesis that dopaminergic medication more readily compensates for intensive aspects of movement (such as speed), than for coordinative aspects (such as coordination of different limb segments) (Schettino et al., Exp Brain Res 168:186-202, 2006). We tested this hypothesis on rhythmic, continuous movements of the forearm. In our task, target peak speed and amplitude, availability of visual feedback, and medication state (on/off) were varied. We found, consistent with the discrete-movement results, that peak speed (intensive aspect) was normalized by medication, while accuracy, which required coordination of speed and amplitude modulation (coordinative aspect), was not normalized by dopaminergic treatment. However, our findings that amplitude, an intensive aspect of movement, was also not normalized by medication, suggests that a simple pathway gain increase does not act to remediate all intensive aspects of movement to the same extent. While it normalized movement peak speed, it did not normalize movement amplitude. Furthermore, we found that when visual feedback was not available, all participants (PD and controls) made faster movements. The effects of dopaminergic medication and availability of visual feedback on movement speed were additive. The finding that movement speed uniformly increased both in the PD and the control groups suggests that visual feedback may be necessary for calibration of peak speed, otherwise underestimated by the motor control system.

EEG correlates of submovements.

Numerous studies on motor control in humans and primates have suggested that the Central Nervous System (CNS) generates and controls continuous movement via discrete, elementary units of movement or submovements. While most studies are based on analysis of kinematic data, investigations of neural correlates have been lacking. To fill this gap we recorded and analyzed kinematic and high-density electroencephalographic (64-channel EEG) data from three right-handed normal adults during a reaching task that required online movement corrections. Each kinematic submovement was accompanied by stereotyped scalp maps. Furthermore, the peaks of event-related potentials (ERP) recorded at electrode C1 (over contralateral motor cortex) were time-locked to kinematic submovement peaks. These results provide further evidence for the hypothesis that the CNS generates and controls continuous movement via discrete submovements. Applications include design of quantitative outcome metrics for motor disorders of neurological origin such as stroke and Parkinson's disease.

Raised corticomotor excitability of M1 forearm area following anodal tDCS is sustained during robotic wrist therapy in chronic stroke.

PURPOSE: Anodal transcranial direct current stimulation (tDCS) can transiently increase corticomotor excitability of intrinsic hand muscles and improve upper limb function in patients with chronic stroke. As a preliminary study, we tested whether increased corticomotor excitability would be similarly observed in muscles acting about the wrist, and remain present during robotic training involving active wrist movements, in six chronic stroke patients with residual motor deficit. METHODS: Transcranial magnetic stimulation (TMS) generated motor evoked potentials (MEP) in the flexor carpi radialis (FCR) and provided a measure of corticomotor excitability and short-interval cortical inhibition (SICI) before and immediately after a period of tDCS (1 mA, 20 min, anode and TMS applied to the lesioned hemisphere), and robotic wrist training (1hr). RESULTS: Following tDCS, the same TMS current strength evoked an increased MEP amplitude (mean 168 +/- 22%SEM; p < 0.05), that remained increased after robot training (166 +/- 23%; p < 0.05). Conditioned MEPs were of significantly lower amplitude relative to unconditioned MEPs prior to tDCS (62 +/- 6%, p < 0.05), but not after tDCS (89 +/- 14%, p = 0.40), or robot training (91 +/- 8%, p = 0.28), suggesting that the increased corticomotor excitability is associated with reduced intracortical inhibition. CONCLUSION: The persistence of these effects after robotic motor training, indicates that a motor learning and retraining program can co-exist with tDCS-induced changes in cortical motor excitability, and supports the concept of combining brain stimulation with physical therapy to promote recovery after brain injury.

The impact of robotic rehabilitation in children with acquired or congenital movement disorders.

AIM: The aim of this study was to evaluate if the robot-mediated therapy (RMT) can yield positive outcomes in children with acquired or congenital upper extremity movement disorders. METHODS: This was an uncontrolled pilot study with pre-post treatment outcome comparison carried out by the Pediatric Rehabilitation Department of a Children's Hospital. The study enrolled 12 children, aged 5 to 15 years, suffering from acquired (at least 12 months post-onset) or congenital upper limb motor impairment. ETIOLOGY: 4 stroke, 6 traumatic brain injuries, and 2 hemiplegic cerebral palsy. RMT was provided 3 times a week for an hour during 6 weeks for a total of 18 robot therapy sessions. The Melbourne Scale (MS) and the upper-extremity subsection of the Fugl-Meyer Assessment (FMA) were used for measurement of impairment. Secondary outcome measurements were made through the Modified Ashworth Scale (MAS); the Reaching Performance Scale (RPS); Parent's Questionnaire, and robot-based evaluation measurements. Specifically, authors compared the smoothness, as measured by the jerk metric, and average speed of unconstrained reaching movements. RESULTS: Pre-post clinical evaluation revealed statistically significant gains for all primary and secondary metrics. In addition, significant improvement of robot-based metrics was observed. The primary outcome measurement mean (SEM) gains were 6.71 (1.29) for MS and 3.33 (0.80) for the FMA. RMT led to spasticity decreases in chronic cases, as shown by the reduction of MAS. It led to improved trunk-upper extremity postural attitude as demonstrated by improved RPS, and it was well accepted by parents and children as observed in the Parent's Questionnaire. CONCLUSIONS: This study suggests that RMT may hold rehabilitative benefits in children suffering from acquired and congenital hemiparesis.

Mechanical arm trainer for the treatment of the severely affected arm after a stroke: a single-blinded randomized trial in two centers.

OBJECTIVE: To test whether training with a new mechanical arm trainer leads to better outcomes than electrical stimulation of the paretic wrist extensors in subacute stroke patients with severe upper limb paresis. Electrical stimulation is a standard and reimbursable form of therapy in Germany. DESIGN: Randomized controlled trial of 54 inpatients enrolled 4-8 wks from stroke onset, mean upper-extremity subsection of Fugl-Meyer assessment (0-66) at admission less than 18. In addition to standard care, all patients practiced 20-30 mins arm trainer or electrical stimulation every workday for 6 wks, totaling 30 sessions. Primary outcome was the Fugl-Meyer assessment, secondary outcomes were the Box and Block test, the Medical Research Council and the modified Ashworth scale, blindly assessed at enrollment, after 6 wks, and at 3-mo follow-up. RESULTS: Both groups were homogeneous at study onset. Shoulder pain occurred in two arm trainer patients. The primary Fugl-Meyer assessment outcome improved for both groups over time (P < 0.001), but this improvement did not differ between groups. The initial (terminal) mean Fugl-Meyer assessment scores were 8.8 +/- 4.8 (19.2 +/- 14.5) for the arm trainer and 8.6 +/- 3.5 (13.6 +/- 7.9) for the electrical stimulation group. No patient could transport a block initially, but at completion significantly more arm trainer patients were able to transport at least three blocks (five vs. zero, P = 0.023). No significant differences were observed between the groups on the secondary Box and Block outcome at follow-up (eight vs. four patients). All Box and Block responders had an initial Fugl-Meyer assessment > or =10. CONCLUSIONS: Arm trainer training did not lead to a superior primary outcome over electrical stimulation training. However, "good performers" on the secondary outcome seemed to benefit more from the arm trainer training.

Changing motor synergies in chronic stroke.

Synergies are thought to be the building blocks of vertebrate movements. The inability to execute synergies in properly timed and graded fashion precludes adequate functional motor performance. In humans with stroke, abnormal synergies are a sign of persistent neurological deficit and result in loss of independent joint control, which disrupts the kinematics of voluntary movements. This study aimed at characterizing training-related changes in synergies apparent from movement kinematics and, specifically, at assessing: 1) the extent to which they characterize recovery and 2) whether they follow a pattern of augmentation of existing abnormal synergies or, conversely, are characterized by a process of extinction of the abnormal synergies. We used a robotic therapy device to train and analyze paretic arm movements of 117 persons with chronic stroke. In a task for which they received no training, subjects were better able to draw circles by discharge. Comparison with performance at admission on kinematic robot-derived metrics showed that subjects were able to execute shoulder and elbow joint movements with significantly greater independence or, using the clinical description, with more isolated control. We argue that the changes we observed in the proposed metrics reflect changes in synergies. We show that they capture a significant portion of the recovery process, as measured by the clinical Fugl-Meyer scale. A process of "tuning" or augmentation of existing abnormal synergies, not extinction of the abnormal synergies, appears to underlie recovery.

Robot-aided sensorimotor arm training improves outcome in patients with chronic stroke.

Thirty patients with chronic stroke received 6 weeks of sensorimotor robotic training in a pilot study that targeted motor function of the affected shoulder and elbow. The impairment and disability scores were stable during a 2-month observation/measurement period, improved significantly by program completion, and remained robust in the 3-month follow-up. Task-specific motor training attenuated a chronic neurologic deficit well beyond the expected period for improvement after stroke.

Assessing the motor status score: a scale for the evaluation of upper limb motor outcomes in patients after stroke.

The Motor Status Scale (MSS) measures shoulder, elbow (maximum score = 40), wrist, hand, and finger movements (maximum score = 42), and expands the measurement of upper extremity impairment and disability provided by the Fugl-Meyer (FM) score. This work examines the interrater reliability and criterion validity of the MSS performed in patients admitted to a rehabilitation hospital 21 +/- 4 days after stroke. Using the MSS and the FM, 7 occupational therapists masked to each other's judgments, evaluated 12 consecutive patients with stroke. Two therapists evaluated 6 additional patients on consecutive days. Intraclass correlation coefficients were significant for each group of raters for the shoulder/elbow and for the wrist/band (P < 0.0001); test-retest measures were also significant for the shoulder/elbow (Pearson correlation coefficient r = 0.99, P < 0.004) and for the wrist/hand (Pearson correlation coefficient r = 0.99, P < 0.003). The internal item consistency for the overall MSS was significant (Cronbach alpha = 0.98, P < 0.0001). Finally the correlation between the MSS and the FM (R2 = 0.964) was significant (P < 0.0001). The MSS affords a reliable and valid assessment of upper limb impairment and disability following stroke.

Robot-aided neurorehabilitation: from evidence-based to science-based rehabilitation.

There is no "magic bullet" in rehabilitation. In the absence of direct neural transplants, neurological rehabilitation is an arduous process. We have pioneered the clinical application of robotics in stroke rehabilitation and have shown evidence of the positive impact of targeted exercise on stroke recovery. In this article, we will review results obtained in the initial clinical trials with 96 stroke patients at the Burke Rehabilitation Hospital. We will provide evidence that robot-aided training enhances recovery, that this enhanced recovery is sustained in the long term, and that this recovery is not due to a general physiological improvement--in fact, it appears to be limb and muscle group specific. An evidence-based approach must now segue into a more scientific approach to stroke rehabilitation. Given the length of the required protocols and patients' variability and limited census, the practical limitations of the evidence-based approach are self-evident and extend trials for years. Each patient and lesion is unique in stroke rehabilitation, so there is no reason to believe that a "one-size-fits-all" optimal treatment exists. To optimize therapy for individual patients, we need science-based models. In this article, we will summarize the scientific tools and models that we are investigating and present some of the results to date.

Is robot-aided sensorimotor training in stroke rehabilitation a realistic option?

Stroke is the leading cause of disability, despite continued advances in prevention and treatment techniques based on novel delivery of new fibrinolytic drugs. Improved medical treatment of the complications caused by acute stroke has contributed to decreased mortality, but 90% of the survivors have significant neurological deficits. Reducing the degree of permanent disability remains the goal of poststroke neuro-rehabilitation programs, and new approaches to impairment reduction through managing sensorimotor experience may contribute further to altering disability. Recent reports from a number of laboratories using enhanced sensorimotor training protocols, particularly those with robotic devices, have indicated modest success in reducing impairment and increasing motor power in the exercised limb of patients with stroke when compared with control individuals. Whether arming the therapist with new tools, especially robotic devices, to treat impairment is a realistic approach to modern interdisciplinary rehabilitation raises questions regarding the added value of impairment reduction, and under what conditions should scientific and clinical development of robotic studies continue.

Procedural motor learning in Parkinson's disease.

We have been investigating motor control and learning in parkinsonian subjects. In the current study, we sought to explore the existence of deficits in procedural motor learning, which is a form of implicit motor learning where skill improves over repetitive blocks of trials. We sought to determine, in particular, whether any such deficit is accentuated during specific types or phases of learning. We would expect that those specific learning tasks would require the greatest participation of the basal ganglia. Numerous studies have found that Parkinson's disease (PD) patients may show deficits in learning. Combined with information about basal ganglia neuronal connections and activity, this led some investigators to suggest that one of the key functions of the basal ganglia is to facilitate learning. To investigate these learning deficits, we used a robotic device to generate conservative force fields that disturbed the subjects' arm movements, thereby generating a "virtual mechanical environment" that subjects learned to manipulate. Movements were successively grouped into blocks comprising five different conditions: motor performance, early learning, late learning, negative transfer, and aftereffect motor performance. Our results with eight right-handed PD subjects and nine age-matched controls showed a relative decrease in the rate of learning for the PD patients in all blocks, but greater differences emerged between groups during novelty phases of learning. In particular, the difference in performance during the negative transfer condition reached statistical significance, suggesting that the basal ganglia might be a key center for "switching" motor patterns. Our results support the hypothesis that deficiencies in procedural motor learning are characteristic of PD. They add to existing evidence which has suggested a key role for the basal ganglia when new sensorimotor mappings are required by novel task environments. Better understanding of these deficits should facilitate the rehabilitation of PD patients.

A novel approach to stroke rehabilitation: robot-aided sensorimotor stimulation.

OBJECTIVE: In patients with stroke, the authors tested whether additional sensorimotor training of the paralyzed or paretic upper limb delivered by a robotic device enhanced motor outcome. METHODS: Fifty-six patients with stroke and hemiparesis or hemiplegia received standard poststroke multidisciplinary rehabilitation, and were randomly assigned either to receive robotic training (at least 25 hours) or exposure to the robotic device without training. Outcomes were assessed by the same masked raters, before treatment began and at the end of treatment, with the upper extremity component of the Fugl-Meyer Motor Assessment, the Motor Status score, the Motor Power score, and Functional Independence Measurement. RESULT: The robot treatment and control group had comparable clinical characteristics, lesion size, and pretreatment impairment scores. By the end of treatment, the robot-trained group demonstrated improvement in motor outcome for the trained shoulder and elbow (Motor Power score, p < 0.001; Motor Status score, p < 0. 01) that did not generalize to untrained wrist and hand. The robot-treated group also demonstrated significantly improved functional outcome (Functional Independence Measurement-Motor, p < 0. 01). CONCLUSION: Robot-delivered quantitative and reproducible sensorimotor training enhanced the motor performance of the exercised shoulder and elbow. The robot-treated group also demonstrated improved functional outcome. When added to standard multidisciplinary rehabilitation, robotics provides novel therapeutic strategies that focus on impairment reduction and improved motor performance.

Increasing productivity and quality of care: robot-aided neuro-rehabilitation.

This paper presents an overview of our research in robot-aided stroke neuro-rehabilitation and recovery. At the onset of this research we had to confront squarely (and solve!) a critical question: If anatomy is destiny, can we influence it? Our efforts over the last five years have been focused on answering this question and we will present a few of our clinical results from over 2,000 hours of robot-aided therapy with 76 stroke patients. To determine if exercise therapy influences plasticity and recovery of the brain following a stroke, we needed the appropriate "microscope" that would allow us to concomitantly control the amount of therapy delivered to a patient, while objectively measuring patient's performance. Back-driveable robots are the key enabling technology. Our results to date using common clinical scales suggest that robot-aided sensorimotor training does have a genuinely positive effect on reduction of impairment and the reorganization of the adult brain. Yet while clinical scales can help us to examine the impact in the neuro-recovery process, their coarse nature requires extensive and time-consuming trials, and on top of that they fail to show us details important for optimizing therapy. Alternative, robot-based scales offer the potential benefit of new finer measurements-and deeper insight into the process of recovery from neurological injury. We also plan to use present technology to establish the practicality and economic feasibility of clinician-supervised, robot-administered therapy, including classroom therapy. We feel quite optimistic that the march of progress will accelerate substantially in the near future and allow us to transfer this technology from the research realm to the everyday treatment of stroke survivors.

Robot training enhanced motor outcome in patients with stroke maintained over 3 years.

In an attempt to improve motor recovery of the upper limb after stroke, we added a robot (MIT-Manus) experience that provided additional goal-directed sensorimotor activity to standard rehabilitation treatments. The first trial produced a significant decrease in motor impairment in the upper limb for the treated group. In re-evaluating 12 of those 20 patients, nearly 3 years later, robot-trained patients showed further significant decreases in impairment measures of the affected limb. The groups were comparable at the start of the study.

Quantization of continuous arm movements in humans with brain injury.

Segmentation of apparently continuous movement has been reported for over a century by human movement researchers, but the existence of primitive submovements has never been proved. In 20 patients recovering from a single cerebral vascular accident (stroke), we identified the apparent submovements that composed a continuous arm motion in an unloaded task. Kinematic analysis demonstrated a submovement speed profile that was invariant across patients with different brain lesions and provided experimental verification of the detailed shape of primitive submovements. The submovement shape was unaffected by its peak speed, and to test further the invariance of shape with speed, we analyzed movement behavior in a patient with myoclonus. This patient occasionally made involuntary shock-like arm movements, which occurred near the maximum capacity of the neuromuscular system, exhibited speed profiles that were comparable to those identified in stroke patients, and were also independent of speed.