Laurie Nichols

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.

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.

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 brains 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.

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

BackgroundConstraint-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. ObjectiveThis 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). ResultsActive 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). ConclusionPairing 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.

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.

Transcranial direct current stimulation to enhance motor function in spinal cord injury: Pilot data

Several lines of evidence indicate that a non-invasive form of brain stimulation called transcranial direct current stimulation (tDCS) can facilitate motor recovery after stroke. However, there is no available data about how tDCS may enhance outcomes of intensive, task-oriented upper extremity (UE) motor training in people with spinal cord injury (SCI). Moreover, there is a lack of effective interventions to enhance recovery of UE motor function after SCI, especially in chronic cases. Thus, we are conducting a double-blind, randomized, controlled study of how tDCS paired with intensive task-oriented training affects UE motor function in subjects with motor incomplete cervical SCI. Our central hypothesis is that subjects who receive anodal tDCS paired with intensive task-oriented training 3 days a week for 8 weeks will have significantly more improved UE motor performance than controls receiving sham tDCS paired with identical training. Furthermore, motor improvement will correlate with corticospinal reorganization (motor maps) measured by transcranial magnetic stimulation (TMS). Outcome measures for motor performance include Spinal Cord Independence Measure-Ill, Canadian Occupational Performance Measure, and Medical Research Council scale administered at baseline, at midpoint, and immediately post-intervention. Here, we present our preliminary results (n=2) of this ongoing study.

Effects of electrode configurations in transcranial direct current stimulation after stroke

Transcranial direct current stimulation (tDCS) is a form of non-invasive brain stimulation that can modulate neuroplasticity (the capacity for brain reorganization). Neuroplastic change correlates with upper extremity (UE) recovery after brain lesions. Different electrode configurations of tDCS paired with UE motor training can have different effects in distinct populations. We are conducting the first randomized, double-blind, placebo-controlled trial to investigate which tDCS configuration may best enhance outcomes of UE motor training for stroke survivors with chronic, severe hemiparesis (i.e., little or no wrist or hand movement). We have assigned subjects to 1 of 4 groups: 1) “Anodal”: anodal tDCS to excite ipsilesional motor cortex; 2) “Cathodal”: cathodal tDCS to inhibit contralesional motor cortex; 3) “Dual”: a simultaneous combination of anodal and cathodal tDCS; or 4) “Sham” tDCS. Intervention (10 sessions) consists of tDCS followed by 3 hours of intensive, task-oriented UE training in each session. Our primary outcome measure is Fugl-Meyer Assessment. Our secondary outcome measures are Action Research Arm Test and Stroke Impact Scale. We have conducted evaluations at baseline and post-intervention. Preliminary results from 26 of (projected) 44 subjects indicate substantially greater improvement for the “Cathodal” group than other groups. These findings differ from evidence about tDCS in rehabilitation of mild-to-moderate hemiparesis. Completion of our study will include full analysis of neuroplastic change associated with intervention.

Dose-response effects of peripheral nerve stimulation and motor training in stroke: Preliminary data

Stroke is one of the most devastating and prevalent diseases. However, efforts to limit tissue damage in acute stroke have met with only minimal success. Therefore, it is of paramount importance to establish effective therapies for use during long-term stages of recovery. Such therapy can capitalize on neuroplastic change (brain reorganization), which has been associated with recovery of function after brain lesions. Intensive, repetitive motor training is a therapeutic intervention that has been shown to support neuroplastic change and improve motor performance after stroke. Likewise, sensory input in the form of peripheral nerve stimulation (PNS) has been shown to upregulate neuroplasticity and improve motor performance after stroke. However, no studies have evaluated how pairing intensive motor training with various PNS intensities and times may affect motor performance, particularly for subjects with severe upper extremity (UE) hemiparesis after stroke. Here, we describe our ongoing study of whether various intensities and times of delivery of PNS relative to motor training will yield differential effects on UE motor function in subjects with chronic, severe motor deficit after stroke. Our results will facilitate development of a dose-response model for PNS paired with intensive, repetitive motor training, which will help optimize this combinatory intervention for stroke survivors with highest need.