Brain Stimulation and Hand Training in Children With Hemiparesis

Synergistic Effect of Combined Transcranial Direct Current Stimulation/Constraint Induced Movement Therapy in Children With Hemiparesis

Hemiparetic cerebral palsy influences motor function in children during development and throughout their lifetime. The deficits one sees are the result both of the congenitally induced brain lesion and the subsequent plasticity that can impair function of the surviving neurons in the damaged brain.

Many current treatments have limited influence on children's neurorecovery. Constraint-induced movement therapy (CIMT) involving constraining the unaffected limb to encourage use of the affected limb has shown promise, yet with new technology revealing the potential to directly influence the brain, there is an urgent need to study the synergy of combined techniques.

Non-invasive brain stimulation (NIBS) as a direct neuromodulatory intervention has the potential to act synergistically with CIMT to influence neurorecovery.

Combining behavioral therapies, constraint-induced movement therapy (CIMT), with a novel form of neuromodulation, transcranial direct current stimulation (tDCS), we investigated the influence of this intervention on improved motor outcomes in children with cerebral palsy. The study hypotheses surround the safety, feasibility and efficacy of combined CIMT and tDCS wherein those children who receive the combined intervention will reveal no major adverse events, yet improved hand function and cortical excitability.

To Note: In addition to the combination of NIBS with CIMT, we also investigated the combination of NIBS with another form of motor intervention, bimanual, or two-handed, training. During bimanual training, children engage both hands in movements. The goal of bimanual training is to teach children how to most effectively use their hands cooperatively. During bimanual training, children play with games and toys that require the use of both hands. Children also practice activities of daily living that require the use of both hands, such as putting hair in a ponytail, tying shoes, and buttoning clothing. N=8 for this pilot study and no randomization. (Burke Medical Research Institute partnered with Columbia University and did a parallel pilot study. N=8 (PIs Friel and Gordon; Protocol BRC449)

Study Overview

• Status: Completed
• Conditions: Pediatric Hemiparesis
• Intervention / Treatment: Device: Transcranial Direct Current Stimulation (tDCS); Device: Placebo Comparator

Detailed Description

We use single-pulse transcranial magnetic stimulation (TMS) to measure the location and strength of brain connections that control hand movements.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
    • Saint Paul, Minnesota, United States, 55101
      • Gillette Children's Specialty Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Hemispheric Stroke or Periventricular Leukomalacia confirmed by most recent MRI or CT radiologic report with resultant congenital hemiparesis
2. ≥ 10 degrees of active motion at the metacarpophalangeal joint
3. Receptive language function to follow two-step commands as evidenced by performance on TOKEN test of intelligence
4. No evidence of seizure activity within the last 2 years
5. Presence of a motor evoked potential from at least the contralesional hemisphere if not both hemispheres
6. Ages 8-21 years
7. Able to give informed assent along with the informed consent of the legal guardian
8. Children who have had surgeries, which may influence motor function eg- tendon transfer, will be included, yet surgical history will be documented and included in any publication within a participant characteristics table.

Exclusion Criteria:

1. Metabolic Disorders
2. Neoplasm
3. Epilepsy
4. Disorders of Cellular Migration and Proliferation
5. Acquired Traumatic Brain Injury
6. Pregnancy
7. Indwelling metal or incompatible medical devices
8. Evidence of skin disease or skin abnormalities
9. Botulinum toxin or Phenol block within [six-months] preceding the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: tDCS/CIMT; Intervention Group will receive 20 minutes of 1.0 mA tDCS to the contralesional hemisphere concurrent with CIMT.	Device: Transcranial Direct Current Stimulation (tDCS); 10 tDCS/CIMT Sessions; Other Names: tDCS; Brain Stimulation
Placebo Comparator: tDCS sham/CIMT; Placebo Group will receive 20 minutes of sham 1.0 mA tDCS to the contralesional hemisphere concurrent with CIMT.	Device: Placebo Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Assisting Hand Assessment (AHA)	Participants were videotaped while performing a bimanual age-appropriate activity. Investigators scored this performance using the Assessment of Assisting Hand (AHA) inventory. The AHA consists of 22 items, each scored on a 4-point scale. Raw scores are a sum of the 22 item scores, ranging from 22-88. Computer software logarithmically transforms ordinal raw scores into a final score. Final scores are reported on a logit-based AHA-unit scale and range from 0 to 100, with higher scores indicating greater ability. Outcome is reported as the change from baseline to 2 weeks and change from baseline to 6 months.	2 weeks, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Canadian Occupational Performance Measurement (COPM)	The COPM is clinician-administered semi-structured interview measuring the participant's perception of satisfaction and performance of personally set goals. There are 3 categories (Self-Care, Productivity, and Leisure) each containing 3 subcategories each for a total of 9 items, which are rated on an ordinal scale from 1 (minimum importance) to 10 (maximum importance). Each of the child's goals are given a satisfaction and performance rating. The average of the satisfaction ratings across all goals is reported as the "average satisfaction score", ranging from 1 to 10, with higher scores indicating a better outcome. Outcome is reported as the change from baseline to 2 weeks and change from baseline to 6 months.	2 weeks, 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Subject Symptom Assessment (SSA) From 2 Weeks to 6 Months	The Subject Symptom Assessment (SSA) is a questionnaire of common side effects reported in the literature that is asked of the child undergoing non-invasive brain stimulation. This measure asks the child to rate if the symptom is present (yes or no) and if it is present, rate the severity using a 1 to 4 scale (1 indicates absent, 2=mild, 3=moderate, 4=severe). Lower values are better as they represent absent or mild symptoms. Outcome is reported as the change in symptom severity from 2 weeks of treatment to 6 months of treatment. This measure is not collected at baseline.	2 weeks, 6 months

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: National Institutes of Health (NIH); Foundation for Physical Therapy, Inc.; Cerebral Palsy International Research Foundation

Publications and helpful links

General Publications

• Gillick B, Menk J, Mueller B, Meekins G, Krach LE, Feyma T, Rudser K. Synergistic effect of combined transcranial direct current stimulation/constraint-induced movement therapy in children and young adults with hemiparesis: study protocol. BMC Pediatr. 2015 Nov 12;15:178. doi: 10.1186/s12887-015-0498-1.
• Lixandrao MC, Stinear JW, Rich T, Chen CY, Feyma T, Meekins GD, Gillick BT. EMG breakthrough during cortical silent period in congenital hemiparesis: a descriptive case series. Braz J Phys Ther. 2020 Jan-Feb;24(1):20-29. doi: 10.1016/j.bjpt.2018.11.002. Epub 2018 Nov 22.

Study record dates

Study Major Dates

• Study Start (Actual): December 31, 2014
• Primary Completion (Actual): June 28, 2017
• Study Completion (Actual): July 10, 2017

Study Registration Dates

• First Submitted: September 18, 2014
• First Submitted That Met QC Criteria: September 23, 2014
• First Posted (Estimate): September 26, 2014

Study Record Updates

• Last Update Posted (Actual): August 18, 2020
• Last Update Submitted That Met QC Criteria: August 6, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Cerebral Palsy; Stroke; Transcranial Direct Current Stimulation; Diffusion Tensor Imaging; Non-Invasive Brain Stimulation; Hemiparesis; Constraint-Induced Movement Therapy; Congenital Hemiparesis; Bimanual Therapy
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Paresis
• Other Study ID Numbers: 1408M53169

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes