Chronic Phase Of Stroke Recovery Research Articles

Validating the Safe and Effective Use of a Neurorehabilitation System (InTandem) to Improve Walking in the Chronic Stroke Population: Usability Study.

Persistent walking impairment following a stroke is common. Although rehabilitative interventions exist, few exist for use at home in the chronic phase of stroke recovery. InTandem (MedRhythms, Inc) is a neurorehabilitation system intended to improve walking and community ambulation in adults with chronic stroke walking impairment. Using design best practices and human factors engineering principles, the research presented here was conducted to validate the safe and effective use of InTandem. In total, 15 participants in the chronic phase of stroke recovery (≥6 months after stroke) participated in this validation study. Participants were scored on 8 simulated use tasks, 4 knowledge assessments, and 7 comprehension assessments in a simulated home environment. The number and types of use errors, close calls, and operational difficulties were evaluated. Analyses of task performances, participant behaviors, and follow-up interviews were conducted to determine the root cause of use errors and difficulties. During this validation study, 93% (14/15) of participants were able to successfully complete the critical tasks associated with the simulated use of the InTandem system. Following simulated use task assessments, participants' knowledge and comprehension of the instructions for use and key safety information were evaluated. Overall, participants were able to find and correctly interpret information in the materials in order to answer the knowledge assessment questions. During the comprehension assessment, participants understood warning statements associated with critical tasks presented in the instructions for use. Across the entire study, 3 "use errors" and 1 "success with difficulty" were recorded. No adverse events, including slips, trips, or falls, occurred in this study. In this validation study, people in the chronic phase of stroke recovery were able to safely and effectively use InTandem in the intended use environment. This validation study contributes to the overall understanding of residual use-related risks of InTandem in consideration of the established benefits.

Patient- and proxy-perceptions on functioning after stroke rehabilitation using the 12-item WHODAS 2.0: a longitudinal cohort study

Purpose To analyse longitudinally patient- and proxy-perceptions on stroke survivors’(SSs’) functioning using the 12-item WHO Disability Assessment Schedule 2.0 (WHODAS) after subacute inpatient stroke rehabilitation. Methods Sixty-five SSs and their significant others(proxies) responded to WHODAS questionnaire at discharge and 9 to 50 months later. Self-WHODAS ratings were compared with corresponding proxy-perceptions and informal ratings on self-reported functional recovery. Results On average, SSs’ functioning improved after discharge, except according to self-WHODAS ratings of those with severe stroke. Individual changes were, however, notable. Association between time and change was statistically insignificant. SSs perceived greatest improvements in walking, household tasks, community life and working ability. The only items showing slight deterioration were emotions and relationships. In parallel, proxies rated all items except emotions and relationships improved. At discharge, proxies rated SSs’ functioning more impaired than SSs themselves, mostly regarding those with severe stroke. Still, inter-rater reliability was very strong and increased significantly with time (ICC 0.799 vs. 0.979 at follow-up). Ninety percent of SSs with improved functioning according to self-WHODAS reported better functioning also in the informal questionnaire. Conclusion WHODAS showed improvements in SSs’ functioning 9-50 months after discharge from subacute stroke rehabilitation. Improvements were in line with proxy-perception and self-reported functional recovery. IMPLICATIONS FOR REHABILITATION Stroke survivors’ functioning improved significantly during the 9-50 months follow-up after subacute inpatient stroke rehabilitation. Stroke survivors perceived slightly less difficulties in their functioning compared to evaluations by proxies. Strong correlation between patient- and proxy-perceptions on stroke survivors’ functioning strengthened from subacute to chronic phase of stroke recovery. The 12-item WHODAS 2.0 seems to be a valuable patient- and proxy-reported outcome measure to assess longitudinal changes in stroke survivors’ functioning after stroke.

Theta-gamma coupling as a cortical biomarker of brain-computer interface-mediated motor recovery in chronic stroke.

Chronic stroke patients with upper-limb motor disabilities are now beginning to see treatment options that were not previously available. To date, the two options recently approved by the United States Food and Drug Administration include vagus nerve stimulation and brain–computer interface therapy. While the mechanisms for vagus nerve stimulation have been well defined, the mechanisms underlying brain–computer interface-driven motor rehabilitation are largely unknown. Given that cross-frequency coupling has been associated with a wide variety of higher-order functions involved in learning and memory, we hypothesized this rhythm-specific mechanism would correlate with the functional improvements effected by a brain–computer interface. This study investigated whether the motor improvements in chronic stroke patients induced with a brain–computer interface therapy are associated with alterations in phase–amplitude coupling, a type of cross-frequency coupling. Seventeen chronic hemiparetic stroke patients used a robotic hand orthosis controlled with contralesional motor cortical signals measured with EEG. Patients regularly performed a therapeutic brain–computer interface task for 12 weeks. Resting-state EEG recordings and motor function data were acquired before initiating brain–computer interface therapy and once every 4 weeks after the therapy. Changes in phase–amplitude coupling values were assessed and correlated with motor function improvements. To establish whether coupling between two different frequency bands was more functionally important than either of those rhythms alone, we calculated power spectra as well. We found that theta–gamma coupling was enhanced bilaterally at the motor areas and showed significant correlations across brain–computer interface therapy sessions. Importantly, an increase in theta–gamma coupling positively correlated with motor recovery over the course of rehabilitation. The sources of theta–gamma coupling increase following brain–computer interface therapy were mostly located in the hand regions of the primary motor cortex on the left and right cerebral hemispheres. Beta–gamma coupling decreased bilaterally at the frontal areas following the therapy, but these effects did not correlate with motor recovery. Alpha–gamma coupling was not altered by brain–computer interface therapy. Power spectra did not change significantly over the course of the brain–computer interface therapy. The significant functional improvement in chronic stroke patients induced by brain–computer interface therapy was strongly correlated with increased theta–gamma coupling in bihemispheric motor regions. These findings support the notion that specific cross-frequency coupling dynamics in the brain likely play a mechanistic role in mediating motor recovery in the chronic phase of stroke recovery.

Exploring the relationship between fatigue and circulating levels of the pro-inflammatory biomarkers interleukin-6 and C-reactive protein in the chronic stage of stroke recovery: A cross-sectional study

BackgroundThe precise mechanisms underlying the aetiology of post-stroke fatigue remain poorly understood. Inflammation has been associated with clinically significant fatigue across a number of neurological disorders; however, at present there is a lack of evidence regarding the association of fatigue and inflammation in the chronic phase of stroke recovery. AimsThe aim of this study was to examine fatigue in a cohort of stroke survivors in the chronic phase of stroke, compared with matched controls, and to explore associations between the pro-inflammatory cytokine interleukin-6, high-sensitivity C-reactive Protein and fatigue. MethodsWe performed an exploratory cross-sectional study of 70 people in the chronic phase of stroke recovery, and 70 age matched controls. Fatigue was assessed using the Fatigue Assessment Scale. Interleukin-6 was measured in serum using a commercially available enzyme immunoassay kit. Both outcome measures were assessed contemporaneously. ResultsClinically significant fatigue, defined as a score ≥24 on the Fatigue Assessment Scale, was reported by 60% of stroke survivors, and 15.7% of controls. The odds of experiencing clinically significant fatigue was 8.04 times higher among stroke survivors compared to control participants (odds ratio 8.045; 95% CI: 3.608, 17.939; P ​< ​0.001). The fatigue score was significantly correlated with the level of both interleukin-6 and high-sensitivity c-reactive protein, however once entered into a linear regression model with cardiovascular covariables, this relationship was no longer statistically significant. ConclusionsThis study shows that fatigue may be associated with systemic inflammation in the chronic phase of stroke. The pathological mechanisms underlying post-stroke fatigue and its clinical implications require further study.

Clinical improvement with intensive robot-assisted arm training in chronic stroke is unchanged by supplementary tDCS.

Intensive robot-assisted arm training in the chronic phase of stroke recovery can lead to clinical improvement. Combinatorial therapeutic approaches are sought to further optimize stroke recovery. Transcranial direct current stimulation (tDCS) is one candidate to combine with robotic training, as transient increases in excitability and improvements in motor behavior have separately been reported. To determine whether tDCS, delivered prior to robotic training, could augment clinical improvement. We conducted a dual-site, randomized controlled trial in 82 chronic ischemic stroke patients (inclusion > 6 m post-injury, dominant hemisphere, first stroke; residual hemiparesis) who were split into two groups to receive tDCS (M1-SO montage, anode ipsilesional, 5×7 cm electrodes, 2 mA, 20 mins) or sham tDCS, prior to robotic upper-limb training (12 weeks; 36 sessions; shoulder-elbow robot or wrist robot on alternating sessions). The primary end-point was taken after 12 weeks of training, and assessed with the Upper Extremity Fugl-Meyer impairment scale (FM). Corticomotor conduction was assessed with transcranial magnetic stimulation (TMS). For the combined group (n = 82; post-training) robotic training increased the FM by 7.36 points compared to baseline (p < 0.0001). There was no difference in the FM increase between the tDCS and sham groups (6.97 and 7.73 respectively, p = 0.46). In both groups, clinically meaningful improvement (≥5 points) from baseline was evident in the majority of patients (56/77), was sustained six months later (54/72), and could be attained in severe, moderate and mild baseline hemiparesis. Clinical improvement was associated with increased excitability in the affected hemisphere as assessed by resting motor threshold (pre-post p = 0.029; pre-post 6 months p = 0.029), but not with threshold-adjusted assessment of MEP amplitude (pre-post p = 0.09; pre-post 6 months p = 0.15). Participants with motor evoked potentials were more likely to improve clinically than those without (17/18, 94%, versus 39/59, 66%, p = 0.018). Our study confirms the benefit of intensive robot-assisted training in stroke recovery, and indicates that conventional tDCS does not confer further advantage to robotic training. We also showed that corticospinal integrity, as assessed by TMS, is a predictor of clinically meaningful response to intensive arm therapy in chronic stroke.

Sensorimotor integration in chronic stroke: Baseline differences and response to sensory training.

The integration of somatosensory information from the environment into the motor cortex to inform movement is essential for motor function. As motor deficits commonly persist into the chronic phase of stroke recovery, it is important to understand potential contributing factors to these deficits, as well as their relationship with motor function. To date the impact of chronic stroke on sensorimotor integration has not been thoroughly investigated. The current study aimed to comprehensively examine the influence of chronic stroke on sensorimotor integration, and determine whether sensorimotor integration can be modified with an intervention. Further, it determined the relationship between neurophysiological measures of sensorimotor integration and motor deficits post-stroke. Fourteen individuals with chronic stroke and twelve older healthy controls participated. Motor impairment and function were quantified in individuals with chronic stroke. Baseline neurophysiology was assessed using nerve-based measures (short- and long-latency afferent inhibition, afferent facilitation) and vibration-based measures of sensorimotor integration, which paired vibration with single and paired-pulse TMS techniques. Neurophysiological assessment was performed before and after a vibration-based sensory training paradigm to assess changes within these circuits. Vibration-based, but not nerve-based measures of sensorimotor integration were different in individuals with chronic stroke, as compared to older healthy controls, suggesting that stroke differentially impacts integration of specific types of somatosensory information. Sensorimotor integration was behaviourally relevant in that it related to both motor function and impairment post-stroke. Finally, sensory training modulated sensorimotor integration in individuals with chronic stroke and controls. Sensorimotor integration is differentially impacted by chronic stroke based on the type of afferent feedback. However, both nerve-based and vibration-based measures relate to motor impairment and function in individuals with chronic stroke.

Patient Engagement Is Related to Impairment Reduction During Digital Game-Based Therapy in Stroke.

Upper limb impairment in the chronic phase of stroke recovery is persistent, disabling, and difficult to treat. The objectives of this study were to determine whether therapeutic enjoyment is related to clinical improvement after upper limb rehabilitation and to assess the feasibility of a therapy gaming system. Ten chronic stroke survivors with persistent upper limb impairment were enrolled in the study. Upper limb impairment was evaluated by using the Fugl-Meyer Assessment of Upper Extremity Function (FMA-UE). The Physical Activity Enjoyment Scale (PACES) assessed the level of therapy enjoyment, and the System Usability Scale (SUS) measured the ease of operation of the game. Upper limb therapy involved 30 minutes of novel digital gaming therapy, three times per week, for 6 weeks. The average improvement in the FMA-UE after the digital gaming therapy was 2.8 (±2.1) points. Participants scored the digital gaming system as having good usability (SUS: 72 ± 7.9), and the physical activity as enjoyable (PACES: 65.8 ± 10.6). There was a strong positive correlation between improvement in the FMA-UE score and the PACES (Spearman's Rho = 0.84; P < 0.002). This pilot study demonstrates the feasibility and potential for improvements in upper limb motor function by using digital gaming in the chronic stroke patient population. The positive correlation found between therapy enjoyment and clinical gains highlights the importance of engagement in therapy to optimize outcomes in chronic stroke survivors.

Contribution of Paretic and Nonparetic Limb Peak Propulsive Forces to Changes in Walking Speed in Individuals Poststroke

Background. Recent rehabilitation efforts after stroke often focus on increasing walking speed because it is associated with quality of life. For individuals poststroke, propulsive force generated from the paretic limb has been shown to be correlated to walking speed. However, little is known about the relative contribution of the paretic versus the nonparetic propulsive forces to changes in walking speed. Objective. The primary purpose of this study was to determine the contribution of propulsive force generated from each limb to changes in walking speed during speed modulation within a session and as a result of a 12-week training program. Methods. Gait analysis was performed as participants (N = 38) with chronic poststroke hemiparesis walked at their self-selected and faster walking speeds on a treadmill before and after a 12-week gait retraining program. Results. Prior to training, stroke survivors increased nonparetic propulsive forces as the primary mechanism to change walking speed during speed modulation within a session. Following gait training, the paretic limb played a larger role during speed modulation within a session. In addition, the increases in paretic propulsive forces observed following gait training contributed to the increases in the self-selected walking speeds seen following training. Conclusions. Gait retraining in the chronic phase of stroke recovery facilitates paretic limb neuromotor recovery and reduces the reliance on the nonparetic limb’s generation of propulsive force to increase walking speed. These findings support gait rehabilitation efforts directed toward improving the paretic limb’s ability to generate propulsive force.

Maximum Walking Speed Is a Key Determinant of Long Distance Walking Function After Stroke

Background: Walking dysfunctions persist following poststroke rehabilitation. A major limitation of current rehabilitation efforts is the inability to identify modifiable deficits that, when improved, will result in the recovery of walking function. Previous studies have relied on cross-sectional analyses to identify deficits to target during walking rehabilitation; however, these studies did not account for the influence of a key covariate – maximum walking speed. Objective: To determine the relationships between commonly studied poststroke variables and the long-distance walking function of individuals poststroke when controlling for maximum walking speed. Methods: Correlation analyses of cross-sectional data from 57 individuals more than 6 months poststroke measured the relationships between standing balance, walking balance, balance self-efficacy, lower extremity motor function, and maximum walking speed versus long-distance walking function. For a subgroup of subjects who completed training, the relationship between changes in maximum walking speed versus changes in long-distance walking function was assessed. Results: Each measurement of interest strongly correlated with long-distance walking function (rs from 0.448 to 0.900, all Ps ≤ .001); however, when controlling for maximum walking speed, none of the other measurements remained related to long-distance walking function. In contrast, when controlling for each of the other measurements, maximum walking speed remained highly related. Moreover, changes in maximum walking speed resulting from training were highly related to changes in long-distance walking function (r = .737, P ≤ .001). Conclusions: For individuals in the chronic phase of stroke recovery, improving maximum walking speed may be necessary to improve long-distance walking function.

Walking Speed and Step Length Asymmetry Modify the Energy Cost of Walking After Stroke

Background. A higher energy cost of walking poststroke has been linked to reduced walking performance and reduced participation in the community. Objective. To determine the contribution of postintervention improvements in walking speed and spatiotemporal gait asymmetry to the reduction in the energy cost of walking after stroke. Methods. In all, 42 individuals with chronic hemiparesis (>6 months poststroke) were recruited to participate in 12 weeks of walking rehabilitation. The energy cost of walking, walking speed, and step length, swing time, and stance time asymmetries were calculated pretraining and posttraining. Sequential regression analyses tested the cross-sectional (ie, pretraining) and longitudinal (ie, posttraining changes) relationships between the energy cost of walking versus speed and each measure of asymmetry. Results. Pretraining walking speed (β = −.506) and swing time asymmetry (β = .403) predicted pretraining energy costs: adjR2 = 0.713; F(3, 37) = 34.05; P < .001. In contrast, change in walking speed (β = .340) and change in step length asymmetry (β = .934) predicted change in energy costs with a significant interaction between these independent predictors: adjR2 = 0.699; F(4, 31) = 21.326; P < .001. Moderation by the direction or the magnitude of pretraining asymmetry was not found. Conclusions. For persons in the chronic phase of stroke recovery, faster and more symmetric walking after intervention appears to be more energetically advantageous than merely walking faster or more symmetrically. This finding has important functional implications, given the relationship between the energy cost of walking and community walking participation.

Preliminary Investigation of an Electromyography-Controlled Video Game as a Home Program for Persons in the Chronic Phase of Stroke Recovery

ObjectiveTo investigate the preliminary effectiveness of surface electromyography (sEMG) biofeedback delivered via interaction with a commercial computer game to improve motor control in chronic stroke survivors. DesignSingle-blinded, 1-group, repeated-measures design: A1, A2, B, A3 (A, assessment; B, intervention). SettingLaboratory and participants' homes. ParticipantsA convenience sample of persons (N=9) between 40 and 75 years of age with moderate to severe upper extremity motor impairment and at least 6 months poststroke completed the study. InterventionThe electromyography-controlled video game system targeted the wrist muscle activation with the goal of increasing selective muscle activation. Participants received several laboratory training sessions with the system and then were instructed to use the system at home for 45 minutes, 5 times per week for the following 4 weeks. Main Outcome MeasuresPrimary outcome measures included duration of system use, sEMG during home play, and pre/post sEMG measures during active wrist motion. Secondary outcomes included kinematic analysis of movement and functional outcomes, including the Wolf Motor Function Test and the Chedoke Arm and Hand Activity Inventory-9. ResultsOne third of participants completed or exceeded the recommended amount of system use. Statistically significant changes were observed on both game play and pre/post sEMG outcomes. Limited carryover, however, was observed on kinematic or functional outcomes. ConclusionsThis preliminary investigation indicates that use of the electromyography-controlled video game impacts muscle activation. Limited changes in kinematic and activity level outcomes, however, suggest that the intervention may benefit from the inclusion of a functional activity component.

Motor imagery during movement activates the brain more than movement alone after stroke: a pilot study.

To examine the neural correlates of motor imagery performed in conjunction with movement of the paretic arm after stroke. Cross-sectional, cohort study. Seven individuals in the chronic phase of stroke recovery (median (range): age: 58 years (37-73); time post-stroke: 9 months (4-42); upper extremity Fugl-Meyer motor score: 48 (36-64)). Participants actively moved the paretic/right arm under two conditions while undergoing functional magnetic resonance imaging. In the motor condition, pronation/supination movements were made in response to a visual cue. In the motor + imagery condition, the same movements were performed in response to a visual cue but the participants were instructed to imagine opening and closing a doorknob during performance of the movement. For the motor condition, the anticipated motor network was activated and included left sensorimotor cortex and right cerebellum. For performance of the same movements during the motor + imagery condition, additional brain regions were significantly engaged including the left inferior parietal lobule and right dorsolateral prefrontal cortex. The addition of motor imagery to movement may provide a practical, accessible way to modulate activity in both the planning and execution components of the motor network after stroke.

Evaluation of white matter myelin water fraction in chronic stroke

Multi-component T2 relaxation imaging (MCRI) provides specific in vivo measurement of myelin water content and tissue water environments through myelin water fraction (MWF), intra/extra-cellular water fraction (I/EWF) and intra/extracellular and global geometric mean T2 (GMT2) times. Quantitative MCRI assessment of tissue water environments has provided new insights into the progression and underlying white matter pathology in neural disorders such as multiple sclerosis. It has not previously been applied to investigate changes in white matter in the stroke-affected brain. Thus, the purposes of this study were to 1) use MCRI to index myelin water content and tissue water environments in the brain after stroke 2) evaluate relationships between MWF and diffusion behavior indexed by diffusion tensor imaging-based metrics and 3) examine the relationship between white matter status (MWF and fractional anisotropy) and motor behavior in the chronic phase of stroke recovery. Twenty individuals with ischemic stroke and 12 matched healthy controls participated. Excellent to good test/re-test and inter-rater reliability was observed for region of interest-based voxelwise MWF data. Reduced MWF was observed in whole-cerebrum white matter (p < 0.001) and in the ipsilesional (p = 0.017) and contralesional (p = 0.037) posterior limb of internal capsule (PLIC) after stroke compared to whole-cerebrum and bilateral PLIC MWF in healthy controls. The stroke group also demonstrated increased I/EWF, I/E GMT2 and global GMT2 times for whole-cerebrum white matter. Measures of diffusion behavior were also significantly different in the stroke group across each region investigated (p < 0.001). MWF was not significantly correlated with specific tensor-based measures of diffusion in the PLIC for either group. Fractional anisotropy in the ipsilesional PLIC correlated with motor behavior in chronic stroke. These results provide novel insights into tissue-specific changes within white matter after stroke that may have important applications for the understanding of the neuropathology of stroke.

The Effects of Repeated Rehabilitation “Tune-Ups” on Functional Recovery After Focal Ischemia in Rats

Background. For most stroke survivors, rehabilitation therapy is the only treatment option available. The beneficial effects of early rehabilitation on neuroplasticity and functional recovery have been modeled in experimental stroke using a combination of enriched environment and rehabilitation. However, the impact of a secondary intervention, such as a periodic return to therapy, remains unclear. Objective. This study examines whether a return to enriched rehabilitation (ie, “tune-up”) can further promote functional recovery or produce beneficial changes in brain plasticity in the chronic phase of stroke recovery. Methods. Rats were exposed to focal ischemia (endothelin-1 applied to forelimb sensorimotor cortex and dorsolateral striatum) and allowed to recover either in standard housing or in a combination of enriched environment and rehabilitative reaching for 9 weeks. Animals were then exposed to rotating periods of standard housing (5 weeks) and intensive “tune-up” therapy consisting of various sensorimotor/cognitive activities (2 weeks). Functional recovery was assessed using the Montoya staircase, beam-traversing, and cylinder tests, and Golgi—Cox analysis was used to examine dendritic complexity in the contralesional forelimb motor cortex. Results. Although early enriched rehabilitation significantly improved sensorimotor function in both the beam and staircase tests, “tune-up” therapy had no effect on recovery. Golgi—Cox analysis revealed no effect of treatment on dendritic complexity. Conclusions. This study reaffirms the benefits of early rehabilitation for functional recovery after stroke. However, “tune-up” therapy provided no benefit in ischemic animals regardless of earlier rehabilitation experience. It is possible that alternative approaches in the chronic phase may prove more effective.