Lynne V. Gauthier

Structural Neuroplastic Change After Constraint-Induced Movement Therapy in Children With Cerebral Palsy

Research from the present laboratory with adult stroke patients showed that structural neuroplastic changes are correlated with clinical improvements due to constraint-induced movement (CI) therapy. This pilot study evaluated whether comparable changes occur in children receiving CI therapy. Ten children (6 boys) with congenital hemiparesis (mean age: 3 years, 3 months) underwent MRI scans 3 weeks before, immediately before, and immediately after receiving 3 weeks of CI therapy. Longitudinal voxel-based morphometry was performed on MRI scans to determine gray matter change. In addition, the Pediatric Motor Activity Log-Revised was administered at these time points to assess arm use in daily life before and after treatment. Children exhibited large improvements after CI therapy in spontaneous use of the more-affected arm (P < .001, d′ = 3.24). A significant increase in gray matter volume occurred in the sensorimotor cortex contralateral to the more-affected arm (P = .04); there was a trend for these changes to be correlated with motor improvement (r = 0.63, P = .063). Trends were also observed for increases in gray matter volume in the ipsilateral motor cortex (P = .055) and contralateral hippocampus (P = .1). No significant gray matter change was seen during the 3 weeks before treatment. These findings suggest that CI therapy produces gray matter increases in the developing nervous system and provide additional evidence that CI therapy is associated with structural remodeling of the human brain while producing motor improvement in patients with disabling central nervous system diseases.

Diffusion tensor imaging study of the response to constraint-induced movement therapy of children with hemiparetic cerebral palsy and adults with chronic stroke.

OBJECTIVE To investigate the relationship of white matter integrity and path of the corticospinal tract (CST) on arm function before and after constraint-induced (CI) movement therapy in children with hemiparetic cerebral palsy (CP) and adults with chronic stroke. DESIGN Study 1 used a multiple-baseline pre-post design. Study 2 was a randomized controlled trial. SETTING Outpatient rehabilitation laboratory. PARTICIPANTS Study 1 included children with hemiparetic CP (n=10; mean age ± SD, 3.2±1.7y). Study 2 included adults with chronic stroke (n=26; mean age ± SD, 65.4±13.6y) who received either CI therapy or a comparison therapy. INTERVENTIONS Children in study 1 received CI therapy for 3.5h/d for 15 consecutive weekdays. Adults in study 2 received either CI therapy or a comparison therapy for 3.5h/d for 10 consecutive weekdays. MAIN OUTCOME MEASURES Diffusion tensor imaging was performed to quantify white matter integrity. Motor ability was assessed in children using the Pediatric Motor Activity Log-Revised and Pediatric Arm Function Test, and in adults with the Motor Activity Log and Wolf Motor Function Test. RESULTS Participants in both studies improved in real-world arm function and motor capacity. Children and adults with disrupted/displaced CSTs and children with reduced fractional anisotropy values were worse on pretreatment tests of motor function than participants with unaltered CSTs. However, neither integrity (fractional anisotropy) nor distorted or disrupted path of the CST affected motor improvement after treatment. CONCLUSIONS Participants who had reduced integrity, displacement, or interruption of their CST performed worse on pretreatment motor testing. However, this had no effect on their ability to benefit from CI therapy. The results for children and adults are consistent with one another.

Virtual reality video games to promote movement recovery in stroke rehabilitation: a guide for clinicians.

After stroke, people often have difficulty moving one arm and hand, but movement can improve with considerable practice. Arm movements may need to be repeated upwards of 2500 times for a person to approach his/her peak level of motor function. Video-gaming technology can effectively deliver engaging, high-repetition movement practice. Use of video games for rehabilitation can be as effective as more conventional approaches.

Computer-aided prediction of extent of motor recovery following constraint-induced movement therapy in chronic stroke

&NA; Constraint‐induced movement therapy (CI therapy) is a well‐researched intervention for treatment of upper limb function. Overall, CI therapy yields clinically meaningful improvements in speed of task completion and greatly increases use of the more affected upper extremity for daily activities. However, individual improvements vary widely. It has been suggested that intrinsic feedback from somatosensation may influence motor recovery from CI therapy. To test this hypothesis, an enhanced probabilistic neural network (EPNN) prognostic computational model was developed to identify which baseline characteristics predict extent of motor recovery, as measured by the Wolf Motor Function Test (WMFT). Individual characteristics examined were: proprioceptive function via the brief kinesthesia test, tactile sensation via the Semmes‐Weinstein touch monofilaments, motor performance captured via the 15 timed items of the Wolf Motor Function Test, stroke affected side. A highly accurate predictive classification was achieved (100% accuracy of EPNN based on available data), but facets of motor functioning alone were sufficient to predict outcome. Somatosensation, as quantified here, did not play a large role in determining the effectiveness of CI therapy.

Video Game Rehabilitation for Outpatient Stroke (VIGoROUS): protocol for a multi-center comparative effectiveness trial of in-home gamified constraint-induced movement therapy for rehabilitation of chronic upper extremity hemiparesis

BackgroundConstraint-Induced Movement therapy (CI therapy) is shown to reduce disability, increase use of the more affected arm/hand, and promote brain plasticity for individuals with upper extremity hemiparesis post-stroke. Randomized controlled trials consistently demonstrate that CI therapy is superior to other rehabilitation paradigms, yet it is available to only a small minority of the estimated 1.2 million chronic stroke survivors with upper extremity disability. The current study aims to establish the comparative effectiveness of a novel, patient-centered approach to rehabilitation utilizing newly developed, inexpensive, and commercially available gaming technology to disseminate CI therapy to underserved individuals. Video game delivery of CI therapy will be compared against traditional clinic-based CI therapy and standard upper extremity rehabilitation. Additionally, individual factors that differentially influence response to one treatment versus another will be examined.MethodsThis protocol outlines a multi-site, randomized controlled trial with parallel group design. Two hundred twenty four adults with chronic hemiparesis post-stroke will be recruited at four sites. Participants are randomized to one of four study groups: (1) traditional clinic-based CI therapy, (2) therapist-as-consultant video game CI therapy, (3) therapist-as-consultant video game CI therapy with additional therapist contact via telerehabilitation/video consultation, and (4) standard upper extremity rehabilitation. After 6-month follow-up, individuals assigned to the standard upper extremity rehabilitation condition crossover to stand-alone video game CI therapy preceded by a therapist consultation. All interventions are delivered over a period of three weeks. Primary outcome measures include motor improvement as measured by the Wolf Motor Function Test (WMFT), quality of arm use for daily activities as measured by Motor Activity Log (MAL), and quality of life as measured by the Quality of Life in Neurological Disorders (NeuroQOL).DiscussionThis multi-site RCT is designed to determine comparative effectiveness of in-home technology-based delivery of CI therapy versus standard upper extremity rehabilitation and in-clinic CI therapy. The study design also enables evaluation of the effect of therapist contact time on treatment outcomes within a therapist-as-consultant model of gaming and technology-based rehabilitation.Trial registrationClinicaltrials.gov, NCT02631850.

Plasma Cytokine Levels Are Related to Brain Volumes in HIV-infected Individuals

HIV-infected individuals frequently exhibit brain dysfunction despite antiretroviral treatment. The neuropathological mechanisms underlying these abnormalities remain unclear, pointing to the importance of identifying biomarkers sensitive to brain dysfunction. We examined 74 medically stable HIV-infected individuals using T1-weighted MRI. Volumes of the cortical grey matter (GM), white matter (WM), caudate, putamen, globus pallidus, thalamus, hippocampus, amygdala, and ventricles were derived using automated parcellation. A panel of plasma cytokines was measured using multiplexed bead array immunoassay. A model selection algorithm was used to select the combination of clinical and cytokine markers that best predicted each brain volumetric measure in a series of linear regression models. Higher CD4 nadir, shorter HIV infection duration, and antiretroviral treatment were significantly related to higher volumes of the putamen, thalamus, hippocampus, and WM. Older age was related to lower volumes in most brain regions and higher ventricular volume. Higher IFN-γ, MCP-1, and TNF-α were related to higher volumes of the putamen, pallidum, amygdala, GM, and WM. Higher IL-1β, IL-6, IL-16, IL-18, IP-10, MIP-1β, and SDF-1α were related to lower volumes of the putamen, pallidum, thalamus, hippocampus, amygdala, GM, and WM; and higher ventricular volume. The current findings provide evidence linking smaller brain volumes to HIV disease history, antiretroviral treatment, and advanced age. Cytokine markers, especially IL-6 and IL-16, showed robust association with brain volumes even after accounting for other clinical variables, demonstrating their utility in examining the mechanisms of HIV-associated brain abnormalities.

Gross motor ability predicts response to upper extremity rehabilitation in chronic stroke

Abstract The majority of rehabilitation research focuses on the comparative effectiveness of different interventions in groups of patients, while much less is currently known regarding individual factors that predict response to rehabilitation. In a recent article, the authors presented a prognostic model to identify the sensorimotor characteristics predictive of the extent of motor recovery after Constraint‐Induced Movement (CI) therapy amongst individuals with chronic mild‐to‐moderate motor deficit using the enhanced probabilistic neural network (EPNN). This follow‐up paper examines which participant characteristics are robust predictors of rehabilitation response irrespective of the training modality. To accomplish this, EPNN was first applied to predict treatment response amongst individuals who received a virtual‐reality gaming intervention (utilizing the same enrollment criteria as the prior study). The combinations of predictors that yield high predictive validity for both therapies, using their respective datasets, were then identified. High predictive classification accuracy was achieved for both the gaming (94.7%) and combined datasets (94.5%). Though CI therapy employed primarily fine‐motor training tasks and the gaming intervention emphasized gross‐motor practice, larger improvements in gross motor function were observed within both datasets. Poorer gross motor ability at pre‐treatment predicted better rehabilitation response in both the gaming and combined datasets. The conclusion of this research is that for individuals with chronic mild‐to‐moderate upper extremity hemiparesis, residual deficits in gross motor function are highly responsive to motor restorative interventions, irrespective of the modality of training.

Gaming for the Brain: Video Gaming to Rehabilitate the Upper Extremity After Stroke

Abstract This chapter discusses the pros and cons of rehabilitation gaming as an approach to upper extremity rehabilitation after a stroke. Gaming as a means of rehabilitation can expand access to rehabilitation services for rural dwellers or those with limited access to transportation. It can expand the scope of care, increase repetitions, and increase engagement. Virtual rehabilitation approaches appear favored over usual care for treating upper limb disability. When adopting virtual reality into rehabilitation programs, it is critical to combine in-game practice with techniques to promote carryover of training into daily living. Through analysis of continuous motion capture, gaming systems have the potential to advance the field by enabling personalized treatment recommendations.

Improved quality of life following constraint-induced movement therapy is associated with gains in arm use, but not motor improvement

ABSTRACT Background. Constraint-induced movement therapy (CI therapy) is one of few treatments for upper extremity (UE) hemiparesis that has been shown to result in motor recovery and improved quality of life in chronic stroke. However, the extent to which treatment-induced improvements in motor function versus daily use of the more affected arm independently contribute to improved quality of life remains largely unexplored. Objective. The objective of this study is to identify whether motor function or daily use of a hemiparetic arm has a greater influence on quality of life after CI therapy. Methods. Two cohorts of participants with chronic stroke received either in-person CI therapy (n = 29) or video-game home-based CI therapy (n = 16). The two cohorts were combined and the motor-related outcomes (Wolf Motor Function Test, Action Research Arm Test, Motor Activity Log [MAL]) and quality of life (Stroke-Specific Quality of Life) were jointly modeled to assess the associations between outcomes. Results. The only outcome associated with improved quality of life was the MAL. Improvements in quality of life were not restricted to motor domains, but generalized to psychosocial domains as well. Conclusions. Results suggest that improved arm use during everyday activities is integral to maximizing quality of life gains during motor rehabilitation for chronic post-stroke UE hemiparesis. In contrast, gains in motor function were not associated with increases in quality of life. These findings further support the need to implement techniques into clinical practice that promote arm use during daily life if improving quality of life is a main goal of treatment. ClinicalTrials.gov Registration Numbers: NCT01725919 and NCT03005457