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.

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.

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.

Transvertebral direct current stimulation paired with locomotor training in chronic spinal cord injury: A case study.

STUDY DESIGN: This double-blind, sham-controlled, crossover case study combined transvertebral direct current stimulation (tvDCS) and locomotor training on a robot-assisted gait orthosis (LT-RGO). OBJECTIVE: Determine whether cathodal tvDCS paired with LT-RGO leads to greater changes in function and neuroplasticity than sham tvDCS paired with LT-RGO. SETTING: University of Kentucky (UK) HealthCare Stroke and Spinal Cord Neurorehabilitation Research at HealthSouth Cardinal Hill Hospital. METHODS: A single subject with motor incomplete spinal cord injury (SCI) participated in 24 sessions of sham tvDCS paired with LT-RGO before crossover to 24 sessions of cathodal tvDCS paired with LT-RGO. Functional outcomes were measured with 10 Meter Walk Test (10MWT), 6 Minute Walk Test (6MWT), Spinal Cord Independence Measure-III (SCIM-III) mobility component, lower extremity manual muscle test (MMT), and Berg Balance Scale (BBS). Corticospinal changes were assessed using transcranial magnetic stimulation. RESULTS: Improvement in 10MWT speed, SCIM-III mobility component, and BBS occurred with both conditions. 6MWT worsened after sham tvDCS and improved after cathodal tvDCS. MMT scores for both lower extremities improved following sham tvDCS but decreased following cathodal tvDCS. Corticospinal excitability increased following cathodal tvDCS but not sham tvDCS. CONCLUSION: These results suggest that combining cathodal tvDCS and LT-RGO may improve functional outcomes, increase corticospinal excitability, and possibly decrease spasticity. Randomized controlled trials are needed to confirm these conclusions. SPONSORSHIP: This publication was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, National Institutes of Health, through Grant UL1TR000117, and the HealthSouth Cardinal Hill Stroke and Spinal Cord Endowment (1215375670).

Long-term cortical reorganization following stroke in a single subject with severe motor impairment.

BACKGROUND: Stroke continues to be a major public health concern in the United States. Motor recovery in the post-acute stages of stroke is possible due to neuroplasticity, or the capacity of the brain to reorganize. OBJECTIVE: This case study tracks neuroplastic and motor change in a subject with severe hemiparesis following an extensive middle cerebral artery stroke. He had absence of ipsilesional motor evoked potentials in early evaluations. This report is unique in that the duration of follow-up evaluation extends nearly 2 years, with evaluations being performed at 7, 9, 10, 13, 20, and 21 months post-stroke. METHODS: At each evaluation we used transcranial magnetic stimulation to track neuroplastic change and the Fugl-Meyer Assessment and the Wolf Motor Function Test to evaluate upper extremity motor performance. RESULTS: The contralesional hemisphere showed dynamic change throughout the study period. In contrast, the ipsilesional hemisphere demonstrated notable change only between 13 and 21 months post-stroke, with the most dramatic change occurring between 20 and 21 months post-stroke. Motor performance generally improved throughout the study period. CONCLUSIONS: Our findings demonstrate that substantial neuroplasticity-mediated motor recovery can occur nearly 2 years after stroke in an individual with severe post-stroke motor impairment.

Behavioral, neurophysiological, and descriptive changes after occupation-based intervention.

OBJECTIVE: We evaluated the effects of occupation-based intervention on poststroke upper-extremity (UE) motor recovery, neuroplastic change, and occupational performance in 1 research participant. METHOD: A 55-yr-old man with chronic stroke and moderately impaired UE motor function participated in 15 sessions of occupation-based intervention in a hospital setting designed to simulate a home environment. We tested behavioral motor function (Fugl-Meyer Assessment, Stroke Impact Scale, Canadian Occupational Performance Measure) and neuroplasticity (transcranial magnetic stimulation [TMS]) at baseline and at completion of intervention. We collected descriptive data on occupational participation throughout the study. RESULTS: All behavioral outcomes indicated clinically relevant improvement. TMS revealed bihemispheric corticomotor reorganization. Descriptive data revealed enhanced occupational performance. CONCLUSION: Occupation-based intervention delivered in a hospital-based, homelike environment can lead to poststroke neuroplastic change, increased functional use of the affected UE, and improved occupational performance.