Despite advances in preventive strategies

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1 Robotic Technology and Stroke Rehabilitation: Translating Research into Practice Susan E. Fasoli, Hermano I. Krebs, and Neville Hogan Research on the effectiveness of robotic therapy for the paretic upper limb after stroke has shown statistically significant reductions in motor impairment during both acute and chronic phases of recovery. Despite growing empirical support for this technology and a stronger focus on optimizing rehabilitation outcomes and productivity, there continues to be a disconnect between research and clinical practice. We review studies on the use of robot-aided neurorehabilitation for the paretic arm after stroke and discuss ways in which this technology may provide opportunities for intensive training that complement more conventional therapy methods. Key words: neurorehabilitation, robotic therapy, stroke, upper limb paresis Despite advances in preventive strategies to reduce the risk of stroke, its incidence continues to rise, with over 700,000 new or recurrent attacks occurring each year. 1 Although functional recovery is the end goal of neurorehabilitation, research indicates that the largest proportion of motor recovery after stroke occurs during the first weeks and months after onset. 2 4 Ongoing cost containment measures and shorter rehabilitation hospitalizations have shifted therapy efforts away from attempts to restore lost motor abilities in the paretic limb and toward the teaching of compensatory techniques to improve functional skills. This change in rehabilitation services has, in many cases, occurred at the expense of impairment reduction. 5 Taub 6 suggested that an emphasis on compensation early after stroke could lead to a pattern of learned nonuse and lower the potential for subsequent gains in motor function of the paretic arm. A growing number of studies have found that intensive, goal-directed therapy improves motor function and cortical reorganization in persons with both acute and long-term impairments after stroke In fact, gains observed in persons with chronic motor impairments indicate that the receptivity to therapeutic intervention does not end after the acute phase of recovery. Rehabilitation technologies, such as robot-aided therapy, provide new options for repetitive movement training that can complement efforts to improve functional performance in daily activities and roles. Although researchers have demonstrated a relationship between intensive rehabilitation (e.g., constraint-induced movement therapy, robotic therapy) and reductions in motor impairment after stroke, 7 16 there is presently a disconnect between this body of evidence and clinical practice. Our aim is to review research on the use of robot-aided neurorehabilitation for the paretic arm after stroke and to discuss ways in which this technology may be integrated into clinical practice. Rehabilitation Robots: Remedial Tools Rehabilitation robots fall into two main classes: robots designed to compensate for lost skills, including manipulation, self-feeding, or mobility 17,18 ; and those developed to remediate or retrain lost motor function after a disabling event such as Susan E. Fasoli, ScD, OTR, is Post-Doctoral Fellow, Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts. Hermano I. Krebs, PhD, is Principal Research Scientist and Lecturer, Department of Mechanical Engineering, Massachusetts Institute of Technology, and is Adjunct Assistant Professor, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, The Winifred Masterson Burke Medical Research Institute, White Plains, New York. Neville Hogan, PhD, is Professor, Department of Mechanical Engineering, and is Professor, Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, Massachusetts. Top Stroke Rehabil 2004;11(4): Thomas Land Publishers, Inc. 11

2 12 TOPICS IN STROKE REHABILITATION/FALL 2004 stroke. Robotic devices in this second class include low-impedance machines specifically designed for rehabilitation and industrial robots that have been reconfigured for therapy purposes (see Table 1). A strength of robots with low mechanical impedance, inertia and friction, such as MIT-Manus and its successor InMotion2, is that these devices are extremely compliant to a person s attempts to move during therapy (i.e., they are backdrivable ) The impedance controller modulates how the robot reacts to mechanical perturbation from a patient or clinician, thereby making it extremely robust to the uncertainties of physical contact. 22,23 Sensors in a low-impedance robot permit accurate and essentially continuous measurement of key variables used to describe motor behavior, namely position, velocity, and force. These objective measures can provide valuable information about changes in motor capacities that underlie functional motor performance. In contrast, industrial robots reconfigured for rehabilitation (e.g., mirror image movement enabler [MIME]) are intrinsically position-controlled machines that do not yield easily to external forces (e.g., human arm). Although these position-controlled robots have been shown to be effective therapy tools, 14,24 they are not as sensitive in recording motor performance because they lack the ability to get out of the way of a patient s attempts to move without assistance. 21 Robots used for remediation purposes can provide intensive, reproducible, and task-specific movement therapy during planar, spatial, unilateral, or bilateral training activities. These robots are able to address a wide range of treatment needs via active, assistive, or strengthening exercise. Unlike other novel therapy approaches like constraint-induced movement therapy (CIMT), robot-aided rehabilitation has been used effectively to treat persons with moderate to severe motor impairments Research indicates that robotic devices have a good potential to provide adjunctive therapy that can complement more functionally based, therapist-generated interventions. In addition to providing new treatment options, this technology may further our understanding of the mechanisms that underlie motor recovery and neural reorganization after stroke. Table 1. Rehabilitation robots for the upper limb Robot name and contact information Assisted Rehabilitation and Measurement (ARM) Guide Contact: David J. Reinkensmeyer, PhD University of California at Irvine Irvine, CA dreinken@uci.edu Mirror Image Motion Enabler MIME Contact: Peter S. Lum, PhD Virginia Commonwealth University, Richmond, VA plum@vcu.edu ARC-MIME Contact: Phybotics Assistive and Therapy Robotics Westmont, NJ info@phybotics.com InMotion2 (successor to MIT-Manus) Contact: Robert Parlow Interactive Motion Technologies Cambridge, MA interactive-motion.com Features/description Trombone-like robotic device designed to mechanically assist linear movements in horizontal plane and at varied degrees of elevation in vertical plane. Statically counterbalanced to eliminate gravitational load on arm. Position controlled PUMA robot that provides passive, active-assisted, active-resisted and unique, bimanual training in threedimensional space (both horizontal and vertical). Combines mechanically assisted linear movements of ARM Guide with control software from MIME robot. Unilateral and bimanual movements can be trained in horizontal and vertical planes. Low endpoint impedance is a key feature of this robot, making it extremely compliant to weak movement attempts. Provides passive, active-assistive, active, and resistive training in horizontal plane. Add-on modules for shoulder movements in vertical plane and wrist/forearm motions are currently being tested with patients. Advantages and disadvantages Robot training is restricted to a linear path and, therefore, does not provide feedback assist to correct errors perpendicular to the movement trajectory. Can provide lowimpedance assistive therapy or resistive training. Less compliant to weak movement attempts during evaluation and treatment, thereby reducing its sensitivity as a measurement tool. Delivers bimanual mirror image training. Initial testing indicates that patient interaction is similar to that of MIME. Intended to provide lower cost, low-impedance robot therapy. Low intrinsic impedance enables precise measure of motor control and performance. Adaptive therapy algorithm automatically modifies assist provided by robot based on patient s motor abilities. Note: This table provides a representative sampling of rehabilitation robots and is not meant to be comprehensive. The robots described here primarily exercise the weak shoulder and elbow with the forearm and hand supported. Optical encoders are used to detect changes in position and velocity, while force sensors measure the forces exerted by patients during evaluation and treatment.

3 Robotic Technology 13 Robot-Aided Neurorehabilitation: Research Findings Researchers have pursued a number of questions that are key to the integration of robotic technology with stroke rehabilitation practice. Although we still do not have answers to all of the questions that follow, evidence in support of rehabilitation robotics is building. Does robotic therapy reduce motor impairment? In the mid-1990s, proof of concept studies began with MIT-Manus to determine whether intensive, robotic therapy was effective in reducing motor impairment after stroke. In this pioneering work, 76 patients receiving interdisciplinary inpatient rehabilitation within the first weeks after stroke were randomly assigned to either a robot treatment or robot exposure group. 11,12 Patients in the robot treatment group were seen for 1 hour a day, 5 days per week. Robot treatment consisted of goal-directed planar reaching tasks that exercised the paretic shoulder and elbow (Figure 1). When the patient was unable to reach toward a designated target during therapy, the robot provided movement assistance similar to that given by a therapist during conventional therapy. Patients assigned to the robot exposure group were seen for 1 hour per week during their inpatient hospitalization. These individuals were asked to practice the same planar reaching tasks performed in the robot therapy group. However, when a patient was unable to reach toward a target, he or she would assist with the unimpaired arm or the technician would help to complete the movement. In this group, the robot did not actively assist the patient s movement attempts. Persons who received robot-aided therapy experienced significantly greater gains in movement and strength of the paretic shoulder and elbow, as measured by the Motor Status Score 25 and Medical Research Council (MRC) Motor Power test. 11,12 It is important to note that improvements in the robot treatment group were sustained up to 3 years after stroke. 26 To determine whether robotic therapy is effective in reducing chronic motor impairments, Figure 1. Person with stroke during robot-aided therapy with MIT-Manus. research has been extended to persons more than 6 months after stroke onset. These studies have the potential to further examine the process of stroke recovery and to determine whether robotic therapy is effective after spontaneous neural recovery is thought to have ended. Fortytwo community-dwelling persons who were 1 to 5 years post stroke were treated with MIT-Manus and its successor InMotion2 three times per week for 6 weeks. 13,16 Based on motor abilities at study admission, participants received either sensorimotor (active-assistive) or progressive-resistive (strengthening) robotic therapy. As in the inpatient trials, combinations of shoulder and elbow movements were trained while the person performed goal-directed tasks visually displayed on a computer monitor. Statistically significant gains were found at discharge, as measured by the Fugl-Meyer Assessment, Motor Status Score for shoulder and elbow, and the MRC Motor Power test. These scores continued to be significantly better than admission at the 4-month follow-up evaluation. Significant reductions observed in shoulder pain at discharge also continued at follow-up. 16 In a separate study, significant benefits were also found in 30 participants with moderate to severe impairments more than 6 months post stroke, who received adaptive sensorimotor robotic therapy via MIT-Manus three times/week for 6 weeks. 15 We can infer that participants were at or

4 14 TOPICS IN STROKE REHABILITATION/FALL 2004 near a plateau in their ability to move the paretic arm at the time of study admission (as indicated by stable pretreatment evaluations). The fact that reductions in chronic motor impairment could be induced after a period of relative stability suggests that there may be windows of opportunity after stroke during which recovery can occur. This research provides further support that the receptivity to therapeutic intervention extends beyond the first 6 to 12 months after stroke and that robot-aided therapy is one tool capable of eliciting positive changes in motor abilities. How does robotic therapy compare to conventional forms of rehabilitation? Lum et al. 14 compared the effects of robot-aided movement training to conventional rehabilitation in persons with residual motor impairments more than 6 months after stroke (n = 27). In this study, treatment duration and intensity were held constant across groups, with all participants receiving 24 one-hour sessions of therapy over a 2-month period. Participants randomly assigned to the robot group practiced reaching, while using the MIME robot, to 12 spatial targets that required combinations of shoulder and elbow movements. Each treatment session progressed from the easiest exercise modes (passive and bimanual) to the most challenging (active-constrained), with the time spent in each mode dependent on ability level. Participants in the control group received conventional neurodevelopmental therapy (NDT) from a certified therapist. This neurodevelopmental treatment focused on postural control, graded arm use during functional tasks, and muscle reeducation to promote control of motor output. Task difficulty was progressed by varying the number of repetitions, weight, or location of objects used. Evaluations by a therapist blinded to group assignment revealed significantly larger improvements in shoulder and elbow scores on the Fugl- Meyer Assessment after the first and second months of treatment and significantly better strength and reach extent at 2 months in the robot group. At the 6-month follow-up, however, group Fugl-Meyer scores were no longer statistically different. Lum et al. 14,27 proposed that different mechanisms might contribute to the patterns of recovery observed in these two groups. Whereas individuals who received robot therapy showed greater trainingrelated gains in strength and reaching extent at 2 months, those in the control group experienced greater long-term benefits from therapist-generated training on how they could exercise on their own. This could have led to better skill acquisition and implementation of home exercise programs in the control group during the follow-up period. We anticipate that the integration of focused robotic therapy with conventional treatment may prove to be better than either intervention alone in restoring function at both the person (strength, reach) and task (self-care) levels. Do patients presenting with more severe motor impairments benefit from this form of intervention? A unique benefit of robot-aided rehabilitation is its adaptability in addressing a wide range of motor impairments. Published studies have included participants with moderate to severe motor impairments at admission, as indicated by the Fugl-Meyer Assessment 11,12,14,28 and NIH Stroke Scale (NIHSS). 15 These persons would not have qualified for other novel interventions, such as CIMT. In research described previously, inpatients who received sensorimotor robotic therapy in early inpatient trials with MIT-Manus had poor admission Fugl-Meyer scores (M = 8.6, SE ± 1.6) but showed statistically significant gains in shoulder and elbow measures at discharge. 11,12,28 Likewise, in a separate study of 30 persons with persistent motor impairments, more than 6 months post stroke, Ferraro et al. 15 reported significant improvements on the Fugl-Meyer and Motor Power tests for the exercised shoulder and elbow, even in persons admitted to the study with severe impairments (NIHSS > 15). In comparison, a study examining the effects of robotic therapy at different impairment levels (n = 46) found that patients with mild and moderate motor impairments at study admission made greater gains on the Fugl-Meyer Assessment than those admitted with more severe limitations. 29 Admittedly, robotic therapy studies have not been strong in demonstrating a relationship

5 Robotic Technology 15 between impairment reductions and improved motor function in the paretic arm. This may be partly attributed to limitations in the functional scales used: the FIM TM * cannot distinguish between improved limb function and compensation; the Wolf Motor Function Test and Rancho Functional Test of the Upper Extremity include a number of tasks that require distal grasp and release, movements that have not been the focus of robotic trials. The fact that persons with mild to severe impairments have experienced motor recovery in the exercised shoulder and elbow has motivated the ongoing development of distal wrist and hand robots for rehabilitation. Based on previous research, we predict that these distal robots will not only have training-specific effects on wrist and hand movements, but will be useful aids in restoring functional use of the paretic limb after stroke. What features of robotic therapy (e.g., assist provided by robot, intensity, duration, etc.) are most critical? Many features of robotic therapy may contribute to enhanced recovery of upper limb motor function. These include task-specific practice, intensity of repetition, robotic assistance, enhanced sensory feedback, continual motivation (because every trial yields a degree of success, even if robot assistance is required), and others. A comprehensive understanding of these key elements is critical not only for robotic therapy, but for all methods of therapeutic intervention. Studies with MIT-Manus have shown that intensive practice of upper limb movements contributes to statistically significant motor recovery after stroke. This effect was apparent in persons soon after stroke onset, 5,11,12 as well as in those with chronic motor impairments. 13,15,16 In a retrospective study of 56 patients who began multidisciplinary inpatient rehabilitation less than 2 weeks after stroke onset, we found that individuals who received conventional therapy plus intensive robotic therapy 5 hours/week for 6 weeks showed statistically significant gains in upper limb motor *FIM TM is a trademark of the Uniform Data System for Medical Rehabilitation, a division of UB Foundation Activities, Inc. abilities during both the first and last 3 weeks of intervention. 28 In comparison, those in the robot exposure group, whose primary treatment was conventional rehabilitation, had little to no change in motor function during weeks 3 through 6. Notably, this 6-week period is approximately twice the present length of stay in inpatient rehabilitation. 30 These results suggest that current health care trends, which limit the duration and intensity of therapy services after the first 3 4 weeks of inpatient rehabilitation, may not adequately address a stroke survivor s potential for motor recovery. Although it is possible that features of robotic therapy other than intensity may have contributed to observed gains in motor performance, it is clear that robot training after the first 3 weeks of inpatient rehabilitation elicited motor recovery in the paretic arm that was not realized through conventional methods alone. This research adds to growing evidence that the course of stroke recovery may be related more to the lack of intensive opportunities to exercise the paretic limb than to neural barriers that cannot be overcome. 31 In an attempt to differentiate whether the mechanical assistance of the robot, rather than repetitive movement attempts by the patient, was a primary contributor to gains in motor ability after stroke, Reinkensmeyer et al. compared the effects of robotic therapy using the ARM (Assisted Rehabilitation and Measurement) Guide with unassisted reaching exercises. 27,32 35 In an ongoing clinical trial, persons with chronic motor impairments more than 6 months post stroke were assigned to either a robot or free-reaching group and received 24 one-hour therapy sessions over a 2-month period. Participants in the robot group received movement assistance from the ARM Guide, as needed, while repetitively reaching toward five targets at different locations and heights. Those in the free-reaching group were asked to perform a matched number of nonrobotic exercises toward targets identical to those practiced by the robot group. Analysis of the first 16 participants revealed that both groups made significant gains in biomechanical measures, including movement speed and muscle tone, as well as functional improvements, as measured by the Rancho Functional Test of the Upper Extremity. 34,35

6 16 TOPICS IN STROKE REHABILITATION/FALL 2004 Although the small number of participants in this study warrants careful interpretation of results, one explanation is that repetitive movement, rather than the assistance provided by the ARM Guide, was the primary contributor to the motor recovery observed in these patients. Another possible explanation is that the robot assist afforded by the ARM Guide was not optimal and that other forms of robotic therapy (bimanual, etc.) may be more effective in providing assisted exercise. Although participants in this research presented with a range of impairment levels and stroke types, future study may reveal that individuals with certain clinical profiles benefit more from robotic assistance than others. From a practical perspective, our studies with MIT- Manus indicate that patient motivation to exercise, and subsequent satisfaction with treatment, is enhanced by the interactive feedback provided during robot tasks. It is possible that the verbal cues and instruction given to the free-reaching group significantly enhanced motivation to succeed in training and thereby influenced motor recovery. Motivational cues may prove to be a critical component of robotic therapy delivered in the clinic or home. Because patients may be using this technology in groups or independently without direct supervision and support by an occupational or physical therapist, this variable deserves further study. Preliminary comparisons of different forms of robotic therapy indicate that the intensity of practice (number of repetitions) is not the only contributor: the type of robotic intervention (adaptive, sensorimotor, strengthening) and duration of therapy also influence the course of motor recovery. 36 Continued research in this area will not only optimize the efficacy of robot-aided rehabilitation, it will also contribute to a scientifically based understanding of the forms of intervention that best meet an individual patient s rehabilitation needs. Translating Research Findings to Clinical Practice: Applications for Robotic Therapy Ultimately, clinical acceptance of robotic technology will depend upon the capability of these devices to offer benefits that are not easily achieved by additional conventional therapy. 27 Apparent strengths include automated practice of repetitive movement patterns, programmable levels of assistive or resistive training to meet a variety of patient needs, and objective evaluation of motor abilities, such as range of motion, speed, smoothness, and strength. In addition, the sensing capabilities of rehabilitation robots allow them to provide specific feedback concerning knowledge of performance and knowledge of results. The therapist can use this information to tailor therapy to the individual s needs by selecting from a range of treatment options. For instance, the robot can be programmed to provide passive movement to maximize range of motion, active-assistive practice of forward reach with elbow extension, or resistance training to improve strength. We envision that robotic technology will become a cost-effective therapeutic tool that not only improves the efficiency and intensity of rehabilitation practice, but also allows the therapist to address impairments in body functions as well as limitations in activities and participation. In their current state, rehabilitation robots have proven to be effective in providing intensive, task-specific movement therapy for the shoulder and elbow. Commercially available robots (e.g., InMotion2 and ARC-MIME 27,37 ) are gradually being integrated into clinical practice. In fact, Burke Rehabilitation Hospital in White Plains, New York, is among the first in the country to implement robotic training via InMotion2 in conjunction with conventional therapy. A newly developed extension for InMotion2 that delivers robot-aided spatial exercises for the impaired shoulder is currently being tested. 38 In addition, a grasp sensor that can monitor active grasp and release abilities during proximal training has recently come online and is expected to elicit distal activation during robotic reaching tasks. Clinical testing of a unique three degree of freedom (DOF) wrist robot has begun at the Massachusetts Institute of Technology, and its implementation in the therapy clinic is anticipated in the near future. Given the integral role of the hand in upper limb function, actuated robots to deliver hand movement therapy have become tar-

7 Robotic Technology 17 gets for future research. We forsee the use of robotic technology in rehabilitation hospitals and clinics, subacute skilled nursing facilities that deliver comprehensive therapy services, acute care hospitals that provide outpatient services, and the home when combined with telerehabilitation services. 42 The implementation of robotic therapy in these settings could enhance treatment intensity across the continuum of care and could improve therapist efficiency. The need for manual manipulation by the therapist could be alleviated (the robot can provide repetitive exercise), and new opportunities for high-quality, intensive group therapy would be created. Use of rehabilitation robots to improve biomechanical abilities, such as range of motion, coordination, and strength, would allow therapists more time to apply their expertise in teaching patients how to use new or relearned motor skills in the context of functional activities. If this integrated treatment approach expedites functional recovery while improving motor abilities, health care costs could be decreased and patient satisfaction would likely rise. The benefits of robotic rehabilitation have been studied mostly in persons diagnosed with stroke, due to its high incidence and prevalence. However, these robotic tools may also prove effective in other diagnostic groups. Antigravity devices, including vertical and spatial robots, could be well suited for therapy after orthopedic conditions, such as shoulder replacement or arthroscopic surgery, in addition to a wide range of neurologically based movement disorders. Currently available devices might be used to facilitate motor recovery after traumatic brain injury, enhance coordination and reduce rigidity seen in Parkinson s disease, and build endurance for upper limb activities in persons with multiple sclerosis or Guillain-Barré syndrome. Newly developed wrist robots may prove to be effective in reducing motor impairment after stroke and may also be beneficial in retraining wrist extension and tenodesis grasp after spinal cord injury or restoring mobility and strength after orthopedic injuries, such as Colles fracture. Rehabilitation robots can be extremely versatile in delivering therapist-prescribed interventions because a large number of treatment variables (e.g., the number of repetitions, level of resistance, range, direction, and speed of movement) may be programmed with relative ease. We anticipate that the options for intensive, reproducible movement therapy afforded by this technology will far surpass those currently available in the clinic. The reliability of subjective, therapist-administered evaluations is a common concern during conventional rehabilitation practice. The clinical scales used to rate performance are often imprecise and open to interpretation by the evaluator. Although subjective measures may suffice when rating the amount of assistance needed to complete basic self-care activities, they can be less reliable when rating changes in motor functions, such as strength, muscle tone, or quality of reach. A strength of robotic technology is its ability to objectively and quantitatively measure changes in motor performance during the course of rehabilitation. In particular, low-impedance machines are highly sensitive to detecting changes in the movement kinematics and forces that underlie functional motor performance. Examples include the speed and accuracy of movement, interjoint coordination, and motor power. The field of rehabilitation is striving to quantify the relationships between impairment, rehabilitation practice, and functional outcomes, but to date the availability of precise evaluation tools has been limited. Although functional abilities are thought to be hierarchically structured, with lower level capacities contributing to higher level motor functions, these relationships are not well defined. Valid and reliable robotic measures may strengthen our scientific knowledge of motor processes and the effects of rehabilitation on recovery of function. In addition, data from robotic evaluations can be used clinically to quantify patient progress and substantiate the need for continued intervention. Conclusion Research trials have shown that rehabilitation robotics provide safe and intensive task-specific training for the upper limb that cannot readily be delivered with conventional therapy methods. Robotic devices are unique in their ability to reproducibly evaluate and treat the full range of motor impairments after stroke, from mild to

8 18 TOPICS IN STROKE REHABILITATION/FALL 2004 severe. Although the effectiveness of robotic therapy has been primarily tested in persons diagnosed with stroke in rehabilitation hospitals, we predict that this technology will become instrumental in treating a wide range of orthopedic and neurologic disorders across the continuum of care, from acute care hospitals to home and outpatient settings. To holistically address limitations in body functions, activities, and participation, 43 the integration of novel technologies with conventional rehabilitation methods seems prudent. Researchers must work closely with clinicians to connect empirical studies with clinical practice. During this process, clinicians can provide important insights to help identify relevant research questions and researchers can recommend ways to deliver evidencebased practice that links neuromotor recovery with functional outcomes. In a time of unprecedented health care reforms and greater focus on increased therapist productivity, this level of collaboration is even more important. By linking scientific knowledge with clinical practice, we will be able to optimize rehabilitation outcomes through more efficient and effective patient care. Acknowledgments This work was supported by the National Institute of Child Health and Human Development of the National Institutes of Health, grants R01- HD and R01-HD-37397, and by the Burke Medical Research Institute. S. Fasoli was supported, in part, by a National Research Service Award from the National Institute of Child Health and Human Development of NIH, grant F32 HD REFERENCES 1. American Heart Association. Heart Disease and Stroke Statistics 2004 Update. Dallas, TX: American Heart Association; Duncan PW, Goldstein LB, Matchar D, Divine GW, Feussner J. Measurement of motor recovery after stroke. Stroke. 1992;23: Hendricks HT, van Limbeek J, Geurts AC, Zwarts MJ. Motor recovery after stroke: a systematic review of the literature. Arch Phys Med Rehabil. 2002;83: Jorgensen HS, Nakayama H, Raaschou H, Vive- Larsen J, Stoier M, Olsen T. Outcome and time course of recovery, Part II: Time course of recovery, the Copenhagen Stroke Study. Arch Phys Med Rehabil. 1995;76: Volpe BT, Krebs HI, Hogan N. Is robot-aided sensorimotor training in stroke rehabilitation a realistic option? Curr Opin Neurol. 2001;14: Taub E, Miller NE, Novack TA, et al. Technique to improve chronic motor deficit after stroke. Arch Phys Med Rehabil. 1993;74: Van der Lee JH, Wagenaar RC, Lankhorst GJ, Vogelaar TW, Deville WL, Bouter LM. Forced use of the upper extremity in chronic stroke patients. Stroke. 1999;30: Liepert J, Bauder H, Wolfgang HR, Miltner WH, Taub E, Weiller C. Treatment-induced cortical reorganization after stroke in humans. Stroke. 2000;31: Dromerick AW, Edwards DF, Hahn M. Does the application of constraint-induced movement therapy during acute rehabilitation reduce arm impairment after ischemic stroke? Stroke. 2000;31: Whitall J, McCombe Waller S, Silver KH, Macko RF. Repetitive bilateral arm training with rhythmic auditory cueing improves motor function in chronic hemiparetic stroke. Stroke. 2000;31: Aisen ML, Krebs HI, Hogan N, McDowell F, Volpe BT. The effect of robot assisted therapy and rehabilitative training on motor recovery following stroke. Arch Neurol. 1997;54: Volpe BT, Krebs HI, Hogan N, Edelstein L, Diels CM, Aisen ML. A novel approach to stroke rehabilitation: robot-aided sensorimotor stimulation. Neurology. 2000;54: Fasoli SE, Krebs HI, Stein J, Frontera WR, Hogan N. Effects of robotic therapy on motor impairment and recovery in chronic stroke. Arch Phys Med Rehabil. 2003;84: Lum PS, Burgar CG, Shor PC, Majmundar M, van der Loos M. Robot-assisted movement training compared with conventional therapy techniques for the rehabilitation of upper-limb motor function after stroke. Arch Phys Med Rehabil. 2002;83: Ferraro M, Palazzolo JJ, Krol J, Krebs HI, Hogan N, Volpe BT. Robot-aided sensorimotor arm training improves outcome in patients with chronic stroke. Neurology. 2003;61: Fasoli SE, Krebs HI, Stein J, Frontera WR, Hughes R, Hogan N. Robotic therapy for chronic motor impairments after stroke: follow-up results. Arch Phys Med Rehabil. 2004;85: Tejima N. Rehabilitation robotics: a review. Adv Robotics. 2000;14: Stefanov DH, Bien Z, Bang W-C. The smart house for older persons and persons with physical disabilities: structure, technology arrangements, and perspectives. IEEE Trans Neural Systems Rehabil Eng.

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