ENHANCE proof-of-concept three-arm randomized trial: effects of reaching training of the hemiparetic upper limb restricted to the spasticity-free elbow range.

Post-stroke motor recovery processes remain unknown. Timescales and patterns of upper-limb (UL) recovery suggest a major impact of biological factors, with modest contributions from rehabilitation. We assessed a novel impairment-based training motivated by motor control theory where reaching occurs within the spasticity-free elbow range. Patients with subacute stroke (≤ 6 month; n = 46) and elbow flexor spasticity were randomly allocated to a 10-day UL training protocol, either personalized by restricting reaching to the spasticity-free elbow range defined by the tonic stretch reflex threshold (TSRT) or non-personalized (non-restricted) and with/without anodal transcranial direct current stimulation. Outcomes assessed before, after, and 1 month post-intervention were elbow flexor TSRT angle and reach-to-grasp arm kinematics (primary) and stretch reflex velocity sensitivity, clinical impairment, and activity (secondary). Results were analyzed for 3 groups as well as those of the effects of impairment-based training. Clinical measures improved in both groups. Spasticity-free range training resulted in faster and smoother reaches, smaller (i.e., better) arm-plane path length, and closer-to-normal shoulder/elbow movement patterns. Non-personalized training improved clinical scores without improving arm kinematics, suggesting that clinical measures do not account for movement quality. Impairment-based training within a spasticity-free elbow range is promising since it may improve clinical scores together with arm movement quality.Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique Identifier: NCT02725853; Initial registration date: 01/04/2016.

Psychometric Properties of a New Measure of Upper Limb Performance in Post-Stroke Individuals: Trunk-Based Index of Performance.

BACKGROUND: Several measures of upper limb (UL) motor tasks have been developed to characterize recovery. However, UL performance and movement quality measures in isolation may not provide a true profile of functional recovery. OBJECTIVE: To investigate the measurement properties of a new trunk-based Index of Performance (IPt) of the UL combining endpoint performance (accuracy and speed) and movement quality (trunk displacement) in stroke. METHODS: Participants with stroke (n = 25, mean time since stroke: 18.7 ± 17.2 months) performed a reaching task over 3 evaluation sessions. The IPt was computed based on Fitts' Law that incorporated endpoint accuracy and speed corrected by the amount of trunk displacement. Test-retest reliability was analyzed using intraclass correlation coefficient (ICC) and Bland-Altman plots. Standard error of measurement (SEM) and Minimal Detectable Change (MDC) were determined. Validity was investigated through the relationship between IPt, Fugl-Meyer Assessment (FMA-UE), and Action Research Arm Test (ARAT), as well as the ability of IPt to distinguish between levels of UL motor impairment severity. RESULTS: Test-retest reliability was excellent (ICC = .908, 95% CI: 0.807-0.96). Bland-Altman did not show systematic differences. SEM and MDC95 were 14% and 39%, respectively. Construct validity was satisfactory. The IPt showed low-to-moderate relationships with FMA-UE (R2 ranged from .236 to .428) and ARAT (R2 ranged from .277 to .306). IPt scores distinguished between different levels of UL severity. CONCLUSIONS: The IPt showed evidence of good reliability, and initial validity. The IPt may be a promising tool for research and clinical settings. Further research is warranted to investigate its validity with additional comparator instruments.

Shared and distinct voxel-based lesion-symptom mappings for spasticity and impaired movement in the hemiparetic upper limb.

Hemiparesis and spasticity are common co-occurring manifestations of hemispheric stroke. The relationship between impaired precision and force in voluntary movement (hemiparesis) and the increment in muscle tone that stems from dysregulated activity of the stretch reflex (spasticity) is far from clear. Here we aimed to elucidate whether variation in lesion topography affects hemiparesis and spasticity in a similar or dis-similar manner. Voxel-based lesion-symptom mapping (VLSM) was used to assess the impact of lesion topography on (a) upper limb paresis, as reflected by the Fugl-Meyer Assessment scale for the upper limb and (b) elbow flexor spasticity, as reflected by the Tonic Stretch Reflex Threshold, in 41 patients with first-ever stroke. Hemiparesis and spasticity were affected by damage to peri-Sylvian cortical and subcortical regions and the putamen. Hemiparesis (but not spasticity) was affected by damage to the corticospinal tract at corona-radiata and capsular levels, and by damage to white-matter association tracts and additional regions in the temporal cortex and pallidum. VLSM conjunction analysis showed only a minor overlap of brain voxels where the existence of damage affected both hemiparesis and spasticity, suggesting that control of voluntary movement and regulation of muscle tone at rest involve largely separate parts of the motor network.

Exercise intensity of the upper limb can be enhanced using a virtual rehabilitation system.

PURPOSE: Motor recovery of the upper limb (UL) is related to exercise intensity, defined as movement repetitions divided by minutes in active therapy, and task difficulty. However, the degree to which UL training in virtual reality (VR) applications deliver intense and challenging exercise and whether these factors are considered in different centres for people with different sensorimotor impairment levels is not evidenced. We determined if (1) a VR programme can deliver high UL exercise intensity in people with sub-acute stroke across different environments and (2) exercise intensity and difficulty differed among patients with different levels of UL sensorimotor impairment. METHODS: Participants with sub-acute stroke (<6 months) with Fugl-Meyer scores ranging from 14 to 57, completed 10 ∼ 50-min UL training sessions using three unilateral and one bilateral VR activity over 2 weeks in centres located in three countries. Training time, number of movement repetitions, and success rates were extracted from game activity logs. Exercise intensity was calculated for each participant, related to UL impairment, and compared between centres. RESULTS: Exercise intensity was high and was progressed similarly in all centres. Participants had most difficulty with bilateral and lateral reaching activities. Exercise intensity was not, while success rate of only one unilateral activity was related to UL severity. CONCLUSION: The level of intensity attained with this VR exercise programme was higher than that reported in current stroke therapy practice. Although progression through different activity levels was similar between centres, clearer guidelines for exercise progression should be provided by the VR application.Implications for rehabilitationVR rehabilitation systems can be used to deliver intensive exercise programmes.VR rehabilitation systems need to be designed with measurable progressions through difficulty levels.

Reaching performance scale for stroke - Test-retest reliability, measurement error, concurrent and discriminant validity.

INTRODUCTION: Post-stroke upper limb motor improvement can be better quantified by describing movement patterns characterizing movement quality and use of compensations. Movement patterns can be described using both kinematic and clinical outcomes. One clinical outcome that assesses movement quality and compensations used for reaching a Close (18 points) and Far target (18 points) is the Reaching Performance Scale for Stroke (RPSS). OBJECTIVE: To estimate the pilot test-retest reliability and validity (concurrent, discriminant) of the RPSS in individuals with chronic stroke. DESIGN: Retrospective data analysis. SETTING: Research laboratory. PARTICIPANTS: Seventy-two individuals with upper limb hemiparesis ≥6 months prior to participation. INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: RPSS Close and Far Target scores. Intraclass correlation coefficients (ICCs) helped assess pilot test-retest reliability on a subset of 14 participants. Concurrent validity was assessed for individual RPSS items with corresponding kinematic outcomes (trunk displacement, shoulder flexion, shoulder horizontal adduction, elbow extension, trajectory straightness) using Pearson correlations. We also ran multiple regression analyses with the RPSS total scores and used kinematic outcomes as the criterion standard. Logistic regression analyses estimated discriminant validity. We divided participants into two groups based on the Fugl-Meyer Assessment (FMA) scores (mild: ≥50/66; moderate-to-severe: ≤49/66). RESULTS: Test-retest reliability was excellent for Close (ICC = 0.98, 95% confidence interval [CI] 0.94-0.99) and Far targets (ICC = 0.98, 95% CI 0.95-0.99). Individual RPSS items for both targets were mildly to moderately correlated with corresponding kinematic values. A combination of trajectory straightness, elbow extension, and trunk displacement explained the majority of the variance in RPSS scores (47%) for both targets. The RPSS scores discriminated between individuals with mild and moderate-to-severe motor impairment for both Close (ExpB = 3.33, P < .001; 95% CI 1.70-6.52) and Far targets (ExpB = 2.59, P < .001, 95% CI 1.65-4.07). Cutoff points for transition between groups were 15.5 (Close target) and 14 (Far target). CONCLUSION: The RPSS is a valid clinical measure with excellent pilot results of test-retest reliability for assessing movement patterns and compensations used for reaching.

Obstacle Avoidance and Dual-Tasking During Reaching While Standing in Patients With Mild Chronic Stroke.

Background. Poststroke individuals use their paretic arms less often than expected in daily life situations, even when motor recovery is scored highly in clinical tests. Real-world environments are often unpredictable and require the ability to multitask and make decisions about rapid and accurate arm movement adjustments. Objective. To identify whether and to what extent cognitive-motor deficits in well-recovered individuals with stroke affect the ability to rapidly adapt reaching movements in changing cognitive and environmental conditions. Methods. Thirteen individuals with mild stroke and 11 healthy controls performed an obstacle avoidance task in a virtual environment while standing. Subjects reached for a virtual juice bottle with their hemiparetic arm as quickly as possible under single- and dual-task conditions. In the single-task condition, a sliding glass door partially obstructed the reaching path of the paretic arm. A successful trial was counted when the subject touched the bottle without the hand colliding with the door. In the dual-task condition, subjects repeated the same task while performing an auditory-verbal working memory task. Results. Individuals with stroke had significantly lower success rates than controls in avoiding the moving door in single-task (stroke: 51.8 ± 21.2%, control: 70.6 ± 12.7%; P = .018) and dual-task conditions (stroke: 40.0 ± 27.6%, control: 65.3 ± 20.0%; P = .015). Endpoint speed was lower in stroke subjects for successful trials in both conditions. Obstacle avoidance deficits were exacerbated by increased cognitive demands in both groups. Individuals reporting greater confidence using their hemiparetic arm had higher success rates. Conclusion. Clinically well-recovered individuals with stroke may have persistent deficits performing a complex reaching task.

Effect of post-stroke spasticity on voluntary movement of the upper limb.

BACKGROUND: Hemiparesis following stroke is often accompanied by spasticity. Spasticity is one factor among the multiple components of the upper motor neuron syndrome that contributes to movement impairment. However, the specific contribution of spasticity is difficult to isolate and quantify. We propose a new method of quantification and evaluation of the impact of spasticity on the quality of movement following stroke. METHODS: Spasticity was assessed using the Tonic Stretch Reflex Threshold (TSRT). TSRT was analyzed in relation to stochastic models of motion to quantify the deviation of the hemiparetic upper limb motion from the normal motion patterns during a reaching task. Specifically, we assessed the impact of spasticity in the elbow flexors on reaching motion patterns using two distinct measures of the 'distance' between pathological and normal movement, (a) the bidirectional Kullback-Liebler divergence (BKLD) and (b) Hellinger's distance (HD). These measures differ in their sensitivity to different confounding variables. Motor impairment was assessed clinically by the Fugl-Meyer assessment scale for the upper extremity (FMA-UE). Forty-two first-event stroke patients in the subacute phase and 13 healthy controls of similar age participated in the study. Elbow motion was analyzed in the context of repeated reach-to-grasp movements towards four differently located targets. Log-BKLD and HD along with movement time, final elbow extension angle, mean elbow velocity, peak elbow velocity, and the number of velocity peaks of the elbow motion were computed. RESULTS: Upper limb kinematics in patients with lower FMA-UE scores (greater impairment) showed greater deviation from normality when the distance between impaired and normal elbow motion was analyzed either with the BKLD or HD measures. The severity of spasticity, reflected by the TSRT, was related to the distance between impaired and normal elbow motion analyzed with either distance measure. Mean elbow velocity differed between targets, however HD was not sensitive to target location. This may point at effects of spasticity on motion quality that go beyond effects on velocity. CONCLUSIONS: The two methods for analyzing pathological movement post-stroke provide new options for studying the relationship between spasticity and movement quality under different spatiotemporal constraints.

Tonic stretch reflex threshold as a measure of spasticity after stroke: Reliability, minimal detectable change and responsiveness.

OBJECTIVE: To determine inter-rater reliability, minimal detectable change and responsiveness of Tonic Stretch Reflex Threshold (TSRT) as a quantitative measure of elbow flexor spasticity. METHODS: Elbow flexor spasticity was assessed in 55 patients with sub-acute stroke by determining TSRT, the angle of spasticity onset at rest (velocity = 0°/s). Elbow flexor muscles were stretched 20 times at different velocities. Dynamic stretch-reflex thresholds, the elbow angles corresponding to the onset of elbow flexor EMG at each velocity, were used for TSRT calculation. Spasticity was also measured with the Modified Ashworth Scale (MAS). In a sub-group of 44 subjects, TSRT and MAS were measured before and after two weeks of an upper-limb intervention. RESULTS: The intraclass correlation coefficient was 0.65 and the 95% minimal detectable change was 32.4°. In the treated sub-group, TSRT, but not MAS significantly changed. TSRT effect size and standardized response mean were 0.40 and 0.35, respectively. Detection of clinically meaningful improvements in upper-limb motor impairment by TSRT change scores ranged from poor to excellent. CONCLUSIONS: Evaluation of stroke-related elbow flexor spasticity by TSRT has good inter-rater reliability. Test responsiveness is low, but better than that of the MAS. SIGNIFICANCE: TSRT may be used to complement current scales of spasticity quantification.

Motor-Equivalent Intersegmental Coordination Is Impaired in Chronic Stroke.

Background. Kinematic abundance permits using different movement patterns for task completion. Individuals poststroke may take advantage of abundance by using compensatory trunk displacement to overcome upper limb (UL) movement deficits. However, movement adaptation in tasks requiring specific intersegment coordination may remain limited. Objective. We tested movement adaptation in both arms of individuals with chronic stroke (n = 16) and nondominant arms of controls (n = 12) using 2 no-vision reaching tasks involving trunk movement (40 trials/arm). Methods. In the "stationary hand task" (SHT), subjects maintained the hand motionless over a target while leaning the trunk forward. In the "reaching hand task" (RHT), subjects reached to the target while leaning forward. For both tasks, trunk movement was unexpectedly blocked in 40% of trials to assess the influence of trunk movement on adaptive arm positioning or reaching. UL sensorimotor impairment, activity, and sitting balance were assessed in the stroke group. The primary outcome measure for SHT was gain (g), defined as the extent to which trunk displacement contributing to hand motion was offset by appropriate changes in UL movements (g = 1: complete compensation) and endpoint deviation for RHT. Results. Individuals poststroke had lower gains and greater endpoint deviation using the more-affected compared with less-affected UL and controls. Those with less sensorimotor impairment, greater activity levels, and better sitting balance had higher gains and smaller endpoint deviations. Lower gains were associated with diminished UL adaptability. Conclusions. Tests of condition-specific adaptability of interjoint coordination may be used to measure UL adaptability and changes in adaptability with treatment.

Relationship Between Spasticity and Upper-Limb Movement Disorders in Individuals With Subacute Stroke Using Stochastic Spatiotemporal Modeling.

BACKGROUND: Spasticity is common in patients with stroke, yet current quantification methods are insufficient for determining the relationship between spasticity and voluntary movement deficits. This is partly a result of the effects of spasticity on spatiotemporal characteristics of movement and the variability of voluntary movement. These can be captured by Gaussian mixture models (GMMs). OBJECTIVES: To determine the influence of spasticity on upper-limb voluntary motion, as assessed by the bidirectional Kullback-Liebler divergence (BKLD) between motion GMMs. METHODS: A total of 16 individuals with subacute stroke and 13 healthy aged-equivalent controls reached to grasp 4 targets (near-center, contralateral, far-center, and ipsilateral). Two-dimensional GMMs (angle and time) were estimated for elbow extension motion. BKLD was computed for each individual and target, within the control group and between the control and stroke groups. Movement time, final elbow angle, average elbow velocity, and velocity smoothness were computed. RESULTS: Between-group BKLDs were much larger than within control-group BKLDs. Between-group BKLDs for the near-center target were lower than those for the far-center and contralateral targets, but similar to that for the ipsilateral target. For those with stroke, the final angle was lower for the near-center target, and the average velocity was higher. Velocity smoothness was lower for the near-center than for the ipsilateral target. Elbow flexor and extensor passive muscle resistance (Modified Ashworth Scale) strongly explained BKLD values. CONCLUSIONS: Results support the view that individuals with poststroke spasticity have a velocity-dependent reduction in active elbow joint range and that BKLD can be used as an objective measure of the effects of spasticity on reaching kinematics.

Personalized upper limb training combined with anodal-tDCS for sensorimotor recovery in spastic hemiparesis: study protocol for a randomized controlled trial.

BACKGROUND: Recovery of voluntary movement is a main rehabilitation goal. Efforts to identify effective upper limb (UL) interventions after stroke have been unsatisfactory. This study includes personalized impairment-based UL reaching training in virtual reality (VR) combined with non-invasive brain stimulation to enhance motor learning. The approach is guided by limiting reaching training to the angular zone in which active control is preserved ("active control zone") after identification of a "spasticity zone". Anodal transcranial direct current stimulation (a-tDCS) is used to facilitate activation of the affected hemisphere and enhance inter-hemispheric balance. The purpose of the study is to investigate the effectiveness of personalized reaching training, with and without a-tDCS, to increase the range of active elbow control and improve UL function. METHODS: This single-blind randomized controlled trial will take place at four academic rehabilitation centers in Canada, India and Israel. The intervention involves 10 days of personalized VR reaching training with both groups receiving the same intensity of treatment. Participants with sub-acute stroke aged 25 to 80 years with elbow spasticity will be randomized to one of three groups: personalized training (reaching within individually determined active control zones) with a-tDCS (group 1) or sham-tDCS (group 2), or non-personalized training (reaching regardless of active control zones) with a-tDCS (group 3). A baseline assessment will be performed at randomization and two follow-up assessments will occur at the end of the intervention and at 1 month post intervention. Main outcomes are elbow-flexor spatial threshold and ratio of spasticity zone to full elbow-extension range. Secondary outcomes include the Modified Ashworth Scale, Fugl-Meyer Assessment, Streamlined Wolf Motor Function Test and UL kinematics during a standardized reach-to-grasp task. DISCUSSION: This study will provide evidence on the effectiveness of personalized treatment on spasticity and UL motor ability and feasibility of using low-cost interventions in low-to-middle-income countries. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT02725853 . Initially registered on 12 January 2016.

Perceptuo-motor planning during functional reaching after stroke.

In healthy young adults, reaching movements are planned such that the initial grasp position on the object is modulated based on the final task goal. This perceptuo-motor coupling has been described as the end-state comfort effect. This study aimed to determine the extent to which visuo-perceptual and motor deficits, but not neglect, due to stroke impact end-state comfort measured as the grasp-height effect. Thirty-four older adults (17 controls, 17 chronic stroke) performed a functional goal-directed two-sequence task with each arm, consisting of reaching and moving a cylindrical object (drain plunger) from an initial to four target platform heights, standardized to body height, in a block randomized sequence. Arm motor impairment (Fugl-Meyer Assessment) and visual-perceptual deficits (Motor-Free Visual Perception Test) were assessed in stroke subjects, and arm and trunk kinematics were assessed in all subjects. The primary outcome measure of the grasp-height effect was the relationship between the grasp heights used at the home position and the final target platform heights. Mixed model analysis was used for data analysis. The grasp-height effect was present in all participants, but decreased in stroke subjects with visuo-perceptual impairments compared to controls. In stroke subjects with sensorimotor impairments alone, indicated by altered kinematics, the grasp-height effect was comparable to controls. This first study examining the grasp-height effect in individuals with stroke provides new knowledge of the impact of visuo-perceptual deficits on movement planning and execution, which may assist clinicians in selecting more effective treatment strategies to improve perceptuo-motor skills and enhance motor recovery.

Upper Limb Obstacle Avoidance Behavior in Individuals With Stroke.

BACKGROUND: Upper limb (UL) poststroke hemiparesis commonly leads to chronic disability. Despite moderate-to-good clinical recovery, many patients with UL hemiparesis still do not fully use their arm in daily tasks. Decreased arm use may be related to deficits in performance of more complex movement than what is usually assessed clinically. OBJECTIVE: To identify differences between poststroke and nondisabled control subjects in making complex corrective movements to avoid an obstacle in the reaching path. METHODS: Subjects rapidly reached for a juice bottle on a refrigerator shelf with their hemiparetic or dominant (controls) arm viewed in a large-screen projected 3D virtual environment. In random trials, a sliding door partially obstructed the reaching path. A successful trial was one in which subjects touched the bottle without their arm or hand hitting the door. RESULTS: Fewer participants with stroke (12%) were successful at a 65% success rate in avoiding the door compared to controls (42%). Subjects with stroke also initiated corrections later (further) in the reaching path (100.7 ± 77.6 mm) compared to controls (51.6 ± 31.0 mm) resulting in a reduced margin of error. While both groups used similar endpoint movement strategies for obstructed reaching, subjects with stroke used less elbow and more trunk movement. Participants who reported being more confident using their hemiparetic arm had higher success rates. CONCLUSION: Arm movement deficits can be identified when complex tasks are evaluated. Deficits in higher-order motor function such as obstacle avoidance behavior may decrease actual arm use in individuals with mild-to-moderate hemiparesis and should be evaluated in routine clinical practice.

Changes in the referent body location and configuration may underlie human gait, as confirmed by findings of multi-muscle activity minimizations and phase resetting.

Locomotion is presumably guided by feed-forward shifts in the referent body location in the desired direction in the environment. We propose that the difference between the actual and the referent body locations is transmitted to neurons that virtually diminish this difference by appropriately changing the referent body configuration, i.e. the body posture at which muscles reach their recruitment thresholds. Muscles are activated depending on the gap between the actual and the referent body configurations resulting in a step being made to minimize this gap. This hypothesis implies that the actual and the referent leg configurations can match each other at certain phases of the gait cycle, resulting in minimization of leg muscle activity. We found several leg configurations at which EMG minima occurred, both during forward and backward gait. It was also found that the set of limb configurations associated with EMG minima can be changed by modifying the pattern of forward and backward gait. Our hypothesis predicts that, in response to perturbations of gait, the rate of shifts in the referent body location can temporarily be changed to avoid falling. The rate influences the phase of rhythmic limb movements during gait. Therefore, following the change in the rate of the referent body location, the whole gait pattern, for all four limbs, will irreversibly be shifted in time (long-lasting and global phase resetting) with only transient changes in the gait speed, swing and stance timing and cycle duration. Aside from transient changes in the duration of the swing and/or stance phase in response to perturbation, few previous studies have documented long-lasting and global phase resetting of human gait in response to perturbation. Such resetting was a robust finding in our study. By confirming the notion that feed-forward changes in the referent body location and configuration underlie human locomotion, this study solves the classical problem in the relationship between stability of posture and gait and advances the understanding of how human locomotion involves the whole body and is accomplished in a spatial frame of reference associated with the environment.

Impact of psychotropic medications on simulated driving: a critical review.

Driving a motor vehicle is central to the functional autonomy of patients with psychiatric illnesses. There have been many studies of the deleterious effects of psychotropic medications such as benzodiazepines, typical antipsychotics and tricyclic antidepressants (TCAs) on human motor skills; however, in the literature little attention has been paid to how such impairment affects driving ability. Computerised driving simulators offer a laboratory-based method of assessing the effects of specific psychotropic medications on driving abilities, in a standardised, controlled and safe manner. The purpose of the present article is to review research undertaken to-date on the effects of psychotropic medications on computer-simulated driving. A search of various databases, including MEDLINE, EMBASE and PsycInfo, was conducted. Forty-one articles assessing the impact of psychotropics on computer-simulated driving were identified. The pooled total number of subjects assessed in these simulator studies was 1336 (mean sample size 30.36 [SD 35.8]). The most common outcome measures in the various studies were speed, steering, deviation from lateral position (tracking, lane drifting), reaction time or braking accuracy, driving errors (e.g. errors in turning, coordination, gap acceptance, signalling, following distance) and vehicle collisions. The results of the studies were quite variable; however, the most common drug-related impairments included those of tracking and reaction time. Benzodiazepines and TCAs were most commonly associated with impairment, although the level of impairment was dependent on the population studied, the dose and the time of testing relative to drug administration. Computer-simulated driving provides a useful tool to research psychotropic-related impairment of driving abilities. Limitations of currently available data include the lack of generalisability, standardisation and small sample sizes.