Effects of dynamic body weight support on functional independence measures in acute ischemic stroke: a retrospective cohort study.

BACKGROUND: Stroke remains a major public health concern in the United States and a leading cause of long-term disability in adults. Dynamic body weight support (DBWS) systems are popular technology available for use in clinical settings such inpatient rehabilitation. However, there remains limited studies in such inpatient settings that compare DBWS to standard of care (SOC) using real world outcome measures. For survivors of acute ischemic stroke, we determine if incorporating a dynamic body weight support (DBWS) system into inpatient therapy offers greater improvement than standard of care (SOC). METHODS: A retrospective chart review included 52 individuals with an acute ischemic stroke admitted to an inpatient rehabilitation facility. Functional Independence Measure (FIM) data, specifically changes in FIM at discharge, served as the primary outcome measure. Patient cohorts received either therapies per SOC or therapies incorporating DBWS. Regardless of cohort group, all patients underwent therapies for 3 h per day for 5 days a week. RESULTS: For both groups, a statistically and clinically significant increase in total FIM (P < 0.0001) was observed at discharge compared to at admission. Improvements for the DBWS group were significantly greater than the SOC group as evidenced by higher gains in total FIM (p = 0.04) and this corresponded to a medium effect size (Cohen's d = 0.58). Among FIM subscores, the DBWS group achieved a significant increase in sphincter control while all other subscore changes remained non-significant. CONCLUSIONS: This preliminary evidence supports the benefit of using DBWS during inpatient rehabilitation in individuals who have experienced an acute ischemic stroke. This may be due to the greater intensity and repetitions of tasks allowed by DBWS. These preliminary findings warrant further investigations on the use of DBWS in inpatient settings.

Functional recovery outcomes following acute stroke is associated with abundance of gut microbiota related to inflammation, butyrate and secondary bile acid.

Accumulating evidence suggests that gut microbes modulate brain plasticity via the bidirectional gut-brain axis and play a role in stroke rehabilitation. However, the microbial species alterations associated with stroke and their correlation with functional outcome measures following acute stroke remain unknown. Here we measure post-stroke gut dysbiosis and how it correlates with gut permeability and cognitive functions in 12 stroke participants, 18 controls with risk factors for stroke, and 12 controls without risk factors. Stool samples were used to measure the microbiome with whole genome shotgun sequencing and leaky gut markers. We genotyped APOE status and measured diet composition and motor, cognitive, and emotional status using NIH Toolbox. We used linear regression methods to identify gut microbial associations with cognitive and emotional assessments. We did not find significance differences between the two control groups. In contrast, the bacteria populations of the Stroke group were statistically dissimilar from the control groups. Relative abundance analysis revealed notable decreases in butyrate-producing microbial taxa, secondary bile acid-producing taxa, and equol-producing taxa. The Stroke group had higher levels of the leaky gut marker alpha-1-antitrypsin in the stool than either of the groups and several taxa including Roseburia species (a butyrate producer) were negatively correlated with alpha-1-antitrypsin. Stroke participants scored lower on memory testing than those in the two control groups. Stroke participants with more Roseburia performed better on the picture vocabulary task; more Bacteroides uniformis (a butyrate producer) and less Escherichia coli (a pro-inflammatory species) reported higher levels of self-efficacy. Intakes of fiber, fruit and vegetable were lower, but sweetened beverages were higher, in the Stroke group compared with controls. Vegetable consumption was correlated with many bacterial changes among the participants, but only the species Clostridium bolteae, a pro-inflammatory species, was significantly associated with stroke. Our findings indicate that stroke is associated with a higher abundance of proinflammatory species and a lower abundance of butyrate producers and secondary bile acid producers. These altered microbial communities are associated with poorer functional performances. Future studies targeting the gut microbiome should be developed to elucidate whether its manipulation could optimize rehabilitation and boost recovery.

Effects of Dynamic Overground Body Weight Support Training During Inpatient Rehabilitation After Traumatic Spinal Cord Injury: A Retrospective Case Series.

ABSTRACT: Rehabilitation strategies after traumatic spinal cord injury aim to maximize functional recovery by applying principles of neuroplasticity via task-specific, repetitive training. Rehabilitation of patients with traumatic spinal cord injury poses unique challenges, including bilateral limb involvement, autonomic dysfunction, loss of proprioception, and potentially spinal precautions/bracing. The purpose of this retrospective case series was to determine whether use of dynamic body weight support would yield greater improvement in functional recovery compared with standard of care in adults with traumatic spinal cord injury. Data were collected from patients with traumatic spinal cord injury who completed inpatient rehabilitation incorporating dynamic body weight support (n = 5) and who completed inpatient rehabilitation without dynamic body weight support (n = 5). The primary outcome measure was the change in Functional Independence Measures. The dynamic body weight support group had a significantly greater improvement in Total Functional Independence Measures and in Functional Independence Measures motor subscale compared with the standard of care group (P = 0.023 and P = 0.033, respectively). This study presents initial evidence that dynamic body weight support therapy during inpatient rehabilitation has the potential to improve functional independence compared with standard of care in patients with traumatic spinal cord injury. Larger prospective randomized studies need to be conducted to expand on these findings.

When brain stimulation backfires: the effects of prefrontal cortex stimulation on impulsivity.

Transcranial direct current stimulation (tDCS) can sometimes cause the opposite of its intended effect. These reverse effects may be related in part to individual differences in personality and neurochemistry. Previous studies have demonstrated that dopamine levels can impact the effects of tDCS. In the present study, 124 healthy participants took the UPPS impulsive behavior scale. Participants then underwent a single, randomized anodal or sham tDCS session on the prefrontal cortex. While the effects of tDCS were still active, they performed the Stop Signal Task, a measure of state impulsivity. tDCS was associated with increased errors on this task in people who had higher scores on the UPPS in two facets of impulsivity that correlate with dopamine levels. tDCS had no effects on people who are low in trait impulsivity. These results suggest that the reverse effects of tDCS could be associated with inter-individual differences in personality and neurochemistry.

Evidence-Based Medicine Training in United States-Based Physiatry Residency Programs.

ABSTRACT: Although the physiatric community increasingly embraces evidence-based medicine (EBM), the current state of EBM training for trainees in physiatry is unclear. The purposes of this article are to report the results of the Association of Academic Physiatrists' surveys of physiatry residency programs in the United States, to discuss the implications of their findings, and to better delineate the "baseline" upon which sound and clear recommendations for systematic EBM training can be made. The two Association of Academic Physiatrists surveys of US physiatry residency programs reveal that most survey respondents report that they include EBM training in their programs that covers the five recommended steps of EBM core competencies. However, although most respondents reported using traditional pedagogic methods of training such as journal club, very few reported that their EBM training used a structured and systematic approach. Future work is needed to support and facilitate physiatry residency programs interested in adopting structured EBM training curricula that include recommended EBM core competencies and the evaluation of their impact.

First-in-Human Studies of MW01-6-189WH, a Brain-Penetrant, Antineuroinflammatory Small-Molecule Drug Candidate: Phase 1 Safety, Tolerability, Pharmacokinetic, and Pharmacodynamic Studies in Healthy Adult Volunteers.

MW01-6-189WH (MW189) is a novel central nervous system-penetrant small-molecule drug candidate that selectively attenuates stressor-induced proinflammatory cytokine overproduction and is efficacious in intracerebral hemorrhage and traumatic brain injury animal models. We report first-in-human, randomized, double-blind, placebo-controlled phase 1 studies to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous doses of MW189 in healthy adult volunteers. MW189 was safe and well tolerated in single and multiple doses up to 0.25 mg/kg, with no clinically significant concerns. The most common drug-related treatment-emergent adverse event was infusion-site reactions, likely related to drug solution acidity. No clinically concerning changes were seen in vital signs, electrocardiograms, physical or neurological examinations, or safety laboratory results. PK analysis showed dose-proportional increases in plasma concentrations of MW189 after single or multiple doses, with approximately linear kinetics and no significant drug accumulation. Steady state was achieved by dose 3 for all dosing cohorts. A pilot pharmacodynamic study administering low-dose endotoxin to induce a systemic inflammatory response was done to evaluate the effects of a single intravenous dose of MW189 on plasma cytokine levels. MW189 treatment resulted in lower levels of the proinflammatory cytokine TNF-α and higher levels of the anti-inflammatory cytokine IL-10 compared with placebo treatment. The outcomes are consistent with the pharmacological mechanism of MW189. Overall, the safety profile, PK properties, and pharmacodynamic effect support further development of MW189 for patients with acute brain injury.

Dynamic body-weight support to boost rehabilitation outcomes in patients with non-traumatic spinal cord injury: an observational study.

BACKGROUND: Dynamic body-weight support (DBWS) may play an important role in rehabilitation outcomes, but the potential benefit among disease-specific populations is unclear. In this study, we hypothesize that overground therapy with DBWS during inpatient rehabilitation yields greater functional improvement than standard-of-care in adults with non-traumatic spinal cord injury (NT-SCI). METHODS: This retrospective cohort study included individuals diagnosed with NT-SCI and undergoing inpatient rehabilitation. All participants were recruited at a freestanding inpatient rehabilitation hospital. Individuals who trained with DBWS for at least three sessions were allocated to the experimental group. Participants in the historical control group received standard-of-care (i.e., no DBWS). The primary outcome was change in the Functional Independence Measure scores (FIMgain). RESULTS: During an inpatient rehabilitation course, participants in the experimental group (n = 11), achieved a mean (SD) FIMgain of 48 (11) points. For the historical control group (n = 11), participants achieved a mean (SD) FIMgain of 36 (12) points. From admission to discharge, both groups demonstrated a statistically significant FIMgain. Between groups analysis revealed no significant difference in FIMgain (p = 0.022; 95% CI 2.0-22) after a post hoc correction for multiple comparisons. In a secondary subscore analysis, the experimental group achieved significantly higher gains in sphincter control (p = 0.011: 95% CI 0.83-5.72) with a large effect size (Cohen's d 1.19). Locomotion subscores were not significantly different (p = 0.026; 95% CI 0.37-5.3) nor were the remaining subscores in self-care, mobility, cognition, and social cognition. CONCLUSIONS: This is the first study to explore the impact of overground therapy with DBWS on inpatient rehabilitation outcomes for persons with NT-SCI. Overground therapy with DBWS appears to significantly improve functional gains in sphincter control compared to the standard-of-care. Gains achieved in locomotion, mobility, cognition, and social cognition did not meet significance. Findings from the present study will benefit from future large prospective and randomized studies.

Impact of motor therapy with dynamic body-weight support on Functional Independence Measures in traumatic brain injury: An exploratory study.

BACKGROUND: Contemporary goals of rehabilitation after traumatic brain injury (TBI) aim to improve cognitive and motor function by applying concepts of neuroplasticity. This can be challenging to carry out in TBI patients with motor, balance, and cognitive impairments. OBJECTIVE: To determine whether use of dynamic body-weight support (DBWS) would allow safe administration of intensive motor therapy during inpatient rehabilitation and whether its use would yield greater improvement in functional recovery than standard-of-care (SOC) therapy in adults with TBI. METHODS: Data in this retrospective cohort study was collected from patients with TBI who receive inpatient rehabilitation incorporating DBWS (n = 6) and who received inpatient rehabilitation without DBWS (SOC, n = 6). The primary outcome measure was the change in Functional Independence Measures (FIM) scores from admission to discharge. RESULTS: There was significant improvement in total FIM scores at discharge compared to admission for both the DBWS (p = 0.001) and SOC (p = 0.005) groups. Overall, the DBWS group had greater improvement in total FIM score and FIM subscales compared to the SOC group. CONCLUSIONS: Our results suggest DBWS has the potential to allow a greater intensity of therapy during inpatient rehabilitation and yield better outcomes compared to SOC in patients with TBI.

Chronicity of Stroke Does Not Affect Outcomes of Somatosensory Stimulation Paired With Task-Oriented Motor Training: A Secondary Analysis of a Randomized Controlled Trial.

OBJECTIVE: To determine whether chronicity influences outcomes of somatosensory stimulation paired with task-oriented motor training for participants with severe-to-moderate upper extremity hemiparesis. DESIGN: Spearman correlations were used to retrospectively analyze outcomes of a randomized trial. SETTING: University research laboratory at a rehabilitation hospital. PARTICIPANTS: Adults, ranging between 3 and 12 months poststroke (N=55). INTERVENTIONS: About 18 sessions pairing either 2 hours of active (n=33) or sham (n=22) somatosensory stimulation with 4 hours of intensive task-oriented motor training. MAIN OUTCOME MEASURES: The Wolf Motor Function Test (primary), Action Research Arm Test, Stroke Impact Scale, and Fugl-Meyer Assessment were collected as outcome measures. Analyses evaluated whether within-group chronicity correlated with pre-post changes on primary and secondary outcome measures of motor performance. RESULTS: Both groups exhibited improvements on all outcome measures. No significant correlations between chronicity poststroke and the amount of motor recovery were found. CONCLUSION: Somatosensory stimulation improved motor recovery compared with sham treatment in cases of severe-to-moderate hemiparesis between 3 and 12 months poststroke; and the extent of recovery did not correlate with baseline levels of stroke chronicity. Future studies should investigate a wider period of inclusion, patterns of corticospinal reorganization, differences between cortical and subcortical strokes, and include long-term follow-up periods.

Absence of Motor-Evoked Potentials Does Not Predict Poor Recovery in Patients With Severe-Moderate Stroke: An Exploratory Analysis.

OBJECTIVE: To better understand the role of the presence or absence of motor-evoked potentials (MEPs) in predicting functional outcomes following a severe-moderate stroke. DESIGN: Retrospective exploratory analysis. We compared the effects of the stimulation condition (active or sham), MEP status (+ or -), and a combination of stimulation condition and MEP status on outcome. Within-group and between-group changes were assessed with longitudinal repeated measures analysis of variance and longitudinal repeated measures analysis of covariance, respectively. The proportions of participants who achieved minimal clinically important differences (MCIDs) for the main outcome measures were calculated. SETTING: University research laboratory within a rehabilitation hospital. PARTICIPANTS: A total of 129 subjects with severe-moderate stroke-related motor impairments who participated in previous studies combining neuromodulation and motor training. INTERVENTIONS: Neuromodulation (active or sham) and motor training. MAIN OUTCOME MEASURES: Fugl-Meyer Assessment (FMA) and Action Research Arm Test (ARAT). RESULTS: When participants were grouped by stimulation condition or MEP status, all groups improved from baseline to immediate postintervention and follow-up evaluations (all P<.05). Analysis by stimulation condition and MEP status found that the MEP-/active group improved by 4.2 points on FMA (P<.0001) and 1.8 on ARAT (P=.003) post intervention. The MEP+/active group improved by 5.7 points on FMA (P<.0001) and 3.9 points on ARAT (P<.0001) post intervention. There were no between-group differences (P>.05). Regarding MCIDs, in the MEP-/active group, 14.5% of individuals reached MCID on FMA and 8.3% on ARAT post intervention. In the MEP+/active group, 33.3% of individuals reached MCID on FMA and 27.3% on ARAT post intervention. CONCLUSION: As expected, the MEP+ group had the greatest improvement in motor function. However, it was shown that individuals without MEPs can also achieve meaningful changes, as reflected by MCID, when neuromodulation is paired with motor training. To our knowledge, this is the first study to differentiate the effects of neuromodulation by MEP status.

Dose-response relationship of transcutaneous spinal direct current stimulation in healthy humans: A proof of concept study.

BACKGROUND: Non-invasive transcranial direct current stimulation has been shown to modulate cortical excitability in various studies. Similarly, recent preliminary studies suggest that transcutaneous spinal direct current stimulation (tsDCS) may engender a modulation effect on spinal and cortical neurons. OBJECTIVE: The purpose of this study was to evaluate the dose-response effects of tsDCS in healthy subjects and thereby lay groundwork for expanding treatment options for patients with spinal cord injury (SCI). METHODS: Nine healthy subjects received each of the following 2 tsDCS conditions: Anodal and cathodal, in random order with at least 1 week washout period between each session. In order to test safety and dose response, various current intensities were used (2, 2.5 and 3 mA) for 20 minutes. The active electrode was placed vertically over T10-T11, and the reference electrode was placed over the left shoulder. To evaluate corticospinal excitability, motor evoked potentials over soleus muscle elicited by transcranial magnetic stimulation were measured. To assess spinal cord excitability, H- and M- wave over soleus muscle to calculate Hmax/ Mmax ratio were measured. RESULTS: Linear regression showed a dose response with cathodal tsDCS on motor evoked potentials measured from the left leg as well as with anodal tsDCS on Hmax/ Mmax ratio measured from the left leg. CONCLUSIONS: These findings indicate tsDCS effects are dose-dependent. These effects should be investigated in a larger sample.

The effect of transcutaneous spinal direct current stimulation on corticospinal excitability in chronic incomplete spinal cord injury.

OBJECTIVES: This study investigated the feasibility of modulating bilateral corticospinal excitability with different polarities of transcutaneous spinal direct current stimulation (tsDCS) in chronic, incomplete spinal cord injury (SCI). METHODS: Six subjects with chronic incomplete SCI (>12 months post injury) participated in this crossover study. Intervention consisted of 3 sessions, separated by at least 1 week, in which each subject received the conditions cathodal, anodal, and sham tsDCS. Stimulation was delivered at 2.5 mA for 20 minutes with the active electrode positioned over the spinous processes of T10-T11 and the reference electrode over left deltoid. To measure the effects of tsDCS on corticospinal excitability, motor evoked potentials (MEPs) from transcranial magnetic stimulation were measured bilaterally from soleus before and after tsDCS. RESULTS: Five subjects completed all 3 sessions. One subject withdrew after 2 sessions due to complications unrelated to the study. MEPs were measurable in 5 subjects. No significant differences in change of MEP amplitudes were found between the 3 conditions. However, there were trends that indicated laterality of response, particularly with cathodal tsDCS increasing corticospinal excitability contralateral to the reference electrode and decreasing corticospinal excitability ipsilateral to the reference electrode. CONCLUSION: Corticospinal excitability may be modulated with laterality by tsDCS in individuals with chronic, incomplete SCI. Further research is needed to 1) determine whether different placement of the reference electrode can lead to uniform modulation bilaterally, and 2) reveal whether these alterations in corticospinal excitability can lead to improved movement function in individuals with chronic, incomplete SCI.

Nerve Stimulation Enhances Task-Oriented Training for Moderate-to-Severe Hemiparesis 3-12 Months After Stroke: A Randomized Trial.

OBJECTIVE: The aim of the study was to determine whether somatosensory stimulation affects outcomes of motor training for moderate-to-severe upper limb hemiparesis less than 12 mos before stroke. DESIGN: Fifty-five adults participated in 18 intervention sessions pairing 2 hours of active (n = 33) or sham (n = 22) somatosensory stimulation with 4 hours of intensive task-oriented motor training. Wolf Motor Function Test, Action Research Arm Test, Fugl-Meyer Assessment, and Stroke Impact Scale were administered at baseline, postintervention, and 1- and 4-mo follow-up. RESULTS: Statistically significant between-groups differences favored the active condition on Wolf Motor Function Test at post (P = 0.04) and Action Research Arm Test at post (P = 0.02), 1 mo (P = 0.01), and 4 mos (P = 0.01) but favored the sham condition on Stroke Impact Scale at 1 mo (P = 0.03). There were no significant between-groups differences on Fugl-Meyer Assessment. CONCLUSIONS: Somatosensory stimulation can improve objective outcomes of motor training for moderate-to-severe hemiparesis less than 12 mos after stroke, although it needs to be determined whether the magnitude of between-groups differences in this study is clinically relevant. Future studies should investigate the intervention's impact on disability and functional recovery for this population as well as neurophysiological mechanisms underlying intervention effects.

Rehabilitation Outcomes in Spinal Abscess Patients With and Without a History of Intravenous Substance Abuse.

OBJECTIVE: The aim of the study was to compare functional outcomes of acute inpatient rehabilitation for spinal epidural abscess patients with and without history of intravenous substance abuse. DESIGN: This is a retrospective case series study in freestanding rehabilitation hospital. METHODS: Charts of 28 spinal epidural abscess patients admitted from January 2012 to September 2015: 13 with intravenous substance abuse and 15 without intravenous substance abuse were reviewed. Both groups received standard-of-care rehabilitation. Statistical analyses of Functional Independence Measure scores were conducted using individual 2 (substance use) × 2 (rehabilitation status) repeated measures analysis of variance. Functional outcomes were defined by total Functional Independence Measure scores as well as motor and cognitive subsets. Length of stay and morphine equivalents were also compared. RESULTS: There were no significant differences between the two groups. There was a significant main effect of treatment on total Functional Independence Measure scores (P < 0.001), Functional Independence Measure motor scores (P < 0.001), and Functional Independence Measure cognitive scores (P < 0.01) from admission to discharge. Subsequent Student's t tests revealed that the scores of both groups significantly improved on all Functional Independence Measure components. There were no group differences on length of stay and morphine equivalents at discharge. CONCLUSIONS: Acute inpatient rehabilitation can effectively improve functional outcomes in spinal epidural abscess patients with or without intravenous substance abuse, even though these two patient groups can vary in clinical factors.

Slow Versus Fast Robot-Assisted Locomotor Training After Severe Stroke: A Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Robot-assisted locomotor training on a bodyweight-supported treadmill is a rehabilitation intervention that compels repetitive practice of gait movements. Standard treadmill speed may elicit rhythmic movements generated primarily by spinal circuits. Slower-than-standard treadmill speed may elicit discrete movements, which are more complex than rhythmic movements and involve cortical areas. OBJECTIVE: Compare effects of fast (i.e., rhythmic) versus slow (i.e., discrete) robot-assisted locomotor training on a bodyweight-supported treadmill in subjects with chronic, severe gait deficit after stroke. METHODS: Subjects (N = 18) were randomized to receive 30 sessions (5 d/wk) of either fast or slow robot-assisted locomotor training on a bodyweight-supported treadmill in an inpatient setting. Functional ambulation category, time up and go, 6-min walk test, 10-m walk test, Berg Balance Scale, and Fugl-Meyer Assessment were administered at baseline and postintervention. RESULTS: The slow group had statistically significant improvement on functional ambulation category (first quartile-third quartile, P = 0.004), 6-min walk test (95% confidence interval [CI] = 1.8 to 49.0, P = 0.040), Berg Balance Scale (95% CI = 7.4 to 14.8, P < 0.0001), time up and go (95% CI = -79.1 to 5.0, P < 0.0030), and Fugl-Meyer Assessment (95% CI = 24.1 to 45.1, P < 0.0001). The fast group had statistically significant improvement on Berg Balance Scale (95% CI = 1.5 to 10.5, P = 0.02). CONCLUSIONS: In initial stages of robot-assisted locomotor training on a bodyweight-supported treadmill after severe stroke, slow training targeting discrete movement may yield greater benefit than fast training.

Safety and improvement of movement function after stroke with atomoxetine: A pilot randomized trial.

BACKGROUND: Intensive, task-oriented motor training has been associated with neuroplastic reorganization and improved upper extremity movement function after stroke. However, to optimize such training for people with moderate-to-severe movement impairment, pharmacological modulation of neuroplasticity may be needed as an adjuvant intervention. OBJECTIVE: Evaluate safety, as well as improvement in movement function, associated with motor training paired with a drug to upregulate neuroplasticity after stroke. METHODS: In this double-blind, randomized, placebo-controlled study, 12 subjects with chronic stroke received either atomoxetine or placebo paired with motor training. Safety was assessed using vital signs. Upper extremity movement function was assessed using Fugl-Meyer Assessment, Wolf Motor Function Test, and Action Research Arm Test at baseline, post-intervention, and 1-month follow-up. RESULTS: No significant between-groups differences were found in mean heart rate (95% CI, -12.4-22.6; p = 0.23), mean systolic blood pressure (95% CI, -1.7-29.6; p = 0.21), or mean diastolic blood pressure (95% CI, -10.4-13.3; p = 0.08). A statistically significant between-groups difference on Fugl-Meyer at post-intervention favored the atomoxetine group (95% CI, 1.6-12.7; p = 0.016). CONCLUSION: Atomoxetine combined with motor training appears safe and may optimize motor training outcomes after stroke.

Time configuration of combined neuromodulation and motor training after stroke: A proof-of-concept study.

BACKGROUND: Intensive motor training is a therapeutic intervention that supports recovery of movement function after stroke by capitalizing on the brain's capacity for neuroplastic change. Peripheral nerve stimulation and transcranial direct current stimulation are neuromodulation techniques that can upregulate neuroplasticity and, in turn, enhance outcomes of motor training after stroke. Few studies have investigated possible adjuvant effects between peripheral nerve stimulation, transcranial direct current stimulation, and intensive motor training. OBJECTIVE: This proof-of-concept study investigated whether timing variations in neuromodulation paired with robot-assisted motor training effect differential outcomes for subjects with chronic, moderate-to-severe upper extremity impairment after stroke. METHODS: Ten subjects in the chronic phase (>12 months after stroke) of recovery completed the study. Subjects received 10 daily sessions of transcranial direct current stimulation either at the start (n = 4) or at the end (n = 6) of peripheral nerve stimulation preceding intensive motor training. Pre-post changes in motor function (Fugl-Meyer Assessment; Stroke Impact Scale) and neuroplasticity (transcranial magnetic stimulation) were assessed by condition. RESULTS: Significant improvement in Stroke Impact Scale (p = 0.02) and no change in Fugl-Meyer Assessment were associated with the start condition. No changes in Stroke Impact Scale and Fugl-Meyer Assessment were associated with the end condition. Only 1 subject in the start group had measurable neuroplastic responses and demonstrated an increase in ipsilesional cortical map volume. Only 1 subject in the end group had measurable neuroplastic responses and demonstrated a decrease in ipsilesional cortical map volume. Opposite shifts in ipsilesional cortical centers of gravity occurred relative to condition. CONCLUSION: In cases of moderate-to-severe impairment after stroke, transcranial direct current stimulation at the start, rather than the end, of peripheral nerve stimulation prior to motor training may effect better functional outcomes. Future research with a larger sample size is needed to validate the findings of this proof-of-concept study.

Nerve Stimulation Enhances Task-Oriented Training in Chronic, Severe Motor Deficit After Stroke: A Randomized Trial.

BACKGROUND AND PURPOSE: A sensory-based intervention called peripheral nerve stimulation can enhance outcomes of motor training for stroke survivors with mild-to-moderate hemiparesis. Further research is needed to establish whether this paired intervention can have benefit in cases of severe impairment (almost no active movement). METHODS: Subjects with chronic, severe poststroke hemiparesis (n=36) were randomized to receive 10 daily sessions of either active or sham stimulation (2 hours) immediately preceding intensive task-oriented training (4 hours). Upper extremity movement function was assessed using Fugl-Meyer Assessment (primary outcome measure), Wolf Motor Function Test, and Action Research Arm Test at baseline, immediately post intervention and at 1-month follow-up. RESULTS: Statistically significant difference between groups favored the active stimulation group on Fugl-Meyer at postintervention (95% confidence interval [CI], 1.1-6.9; P=0.008) and 1-month follow-up (95% CI, 0.6-8.3; P=0.025), Wolf Motor Function Test at postintervention (95% CI, -0.21 to -0.02; P=0.020), and Action Research Arm Test at postintervention (95% CI, 0.8-7.3; P=0.015) and 1-month follow-up (95% CI, 0.6-8.4; P=0.025). Only the active stimulation condition was associated with (1) statistically significant within-group benefit on all outcomes at 1-month follow-up and (2) improvement exceeding minimal detectable change, as well as minimal clinically significant difference, on ≥1 outcomes at ≥1 time points after intervention. CONCLUSIONS: After stroke, active peripheral nerve stimulation paired with intensive task-oriented training can effect significant improvement in severely impaired upper extremity movement function. Further confirmatory studies that consider a larger group, as well as longer follow-up, are needed. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02633215.

Randomized Trial of Peripheral Nerve Stimulation to Enhance Modified Constraint-Induced Therapy After Stroke.

BACKGROUND: Constraint-based therapy and peripheral nerve stimulation can significantly enhance movement function after stroke. No studies have investigated combining these interventions for cases of chronic, mild-to-moderate hemiparesis following stroke. OBJECTIVE: This study aims to determine the effects of peripheral nerve stimulation paired with a modified form of constraint-induced therapy on upper extremity movement function after stroke. Nineteen adult stroke survivors with mild-to-moderate hemiparesis more than 12 mo after stroke received 2 hours of either active (n = 10) or sham (n = 9) peripheral nerve stimulation preceding 4 hours of modified constraint-induced therapy (10 sessions). RESULTS: Active peripheral nerve stimulation enhanced modified constraint-induced therapy more than sham peripheral nerve stimulation (significance at P < 0.05), both immediately after intervention (Wolf Motor Function Test: P = 0.006 (timed score); P = 0.001 (lift score); Fugl-Meyer Assessment: P = 0.022; Action Research Arm Test: P = 0.007) and at 1-mo follow-up (Wolf Motor Function Test: P = 0.025 (timed score); P = 0.007 (lift score); Fugl-Meyer Assessment: P = 0.056; Action Research Arm Test: P = 0.028). CONCLUSION: Pairing peripheral nerve stimulation with modified constraint-induced therapy can lead to significantly more improvement in upper extremity movement function than modified constraint-induced therapy alone. Future research is recommended to help establish longitudinal effects of this paired intervention, particularly as it affects movement function and daily life participation. TO CLAIM CME CREDITS: Complete the self-assessment activity and evaluation online at http://www.physiatry.org/JournalCME CME OBJECTIVES:: Upon completion of this article, the reader should be able to: (1) Understand the role that afferent input plays with regard to movement function; (2) Understand general concepts of delivering modified constraint-based therapy in stroke rehabilitation research; and (3) Understand the rationale for applying an adjuvant intervention to optimize outcomes of constraint-based therapy following stroke. LEVEL: Advanced ACCREDITATION: : The Association of Academic Physiatrists is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The Association of Academic Physiatrists designates this activity for a maximum of 1.5 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity.

Non-invasive brain stimulation and robot-assisted gait training after incomplete spinal cord injury: A randomized pilot study.

BACKGROUND: Locomotor training with a robot-assisted gait orthosis (LT-RGO) and transcranial direct current stimulation (tDCS) are interventions that can significantly enhance motor performance after spinal cord injury (SCI). No studies have investigated whether combining these interventions enhances lower extremity motor function following SCI. OBJECTIVE: Determine whether active tDCS paired with LT-RGO improves lower extremity motor function more than a sham condition, in subjects with motor incomplete SCI. METHODS: Fifteen adults with SCI received 36 sessions of either active (n = 9) or sham (n = 6) tDCS (20 minutes) preceding LT-RGO (1 hour). Outcome measures included manual muscle testing (MMT; primary outcome measure); 6-Minute Walk Test (6MinWT); 10-Meter Walk Test (10MWT); Timed Up and Go Test (TUG); Berg Balance Scale (BBS); and Spinal Cord Independence Measure-III (SCIM-III). RESULTS: MMT showed significant improvements after active tDCS, with the most pronounced improvement in the right lower extremity. 10MWT, 6MinWT, and BBS showed improvement for both groups. TUG and SCIM-III showed improvement only for the sham tDCS group. CONCLUSION: Pairing tDCS with LT-RGO can improve lower extremity motor function more than LT-RGO alone. Future research with a larger sample size is recommended to determine longer-term effects on motor function and activities of daily living.