Priming Effects of Ultra-high Frequency Quattro Pulse Transcranial Brain Stimulation Prior to Hand Motor Function Training in Children With Unilateral Spastic Cerebral Palsy

Study Overview
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Brief Summary
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Unilateral spastic cerebral palsy (USCP) leads to life-long impairment with a hemiparesis of the affected side of the body. Rehabilitation efforts combine evidence based methods such as constrained induced movement therapy (CIMT) or hand-arm bimanual intensive therapy (HABIT) as well as training in daily life activities and psychological support in order to improve participation. It has been tried to enhance hand motor function trainings with non-invasive brain stimulation. However, evidence of this promising approach is limited. This might be due to a non-consideration of the individually different types of cortico-spinal projections to the paretic hand that demonstrated to be of highly relevant for the therapy of these children. Approximately one third of such patients control their paretic hands via crossed projections from the affected hemisphere (CONTRA), while one third uses ipsilateral projections from the contralesional hemisphere (IPSI). This study aims - for the first time - to enhance the effects of the training by priming the primary motor cortex (M1) of the paretic hand with a newly established high frequency quadri-pulse theta burst stimulation (qTBS) in a randomized, patient and evaluator blind, sham-controlled approach, for the first time taking the individual type of cortico-spinal reorganization (CONTRA vs IPSI) into account. This promising and neurophysiologically motivated approach is likely to ameliorate hand function in children with USCP.

Official Title
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Priming Effects of Ultra-high Frequency Quattro Pulse Transcranial Brain Stimulation Prior to Hand Motor Function Training in Children With Unilateral Spastic Cerebral Palsy

Conditions
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Cerebral Palsy, Spastic, Transcranial Magnetic Stimulation, Repetitive

Intervention / Treatment
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* Other: Quadri-pulse theta burst stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Assured diagnosis of USCP. Children aged 6 to 18 years with USCP Dated and signed informed consent of legal guardian, informed assent from minor Exclusion Criteria: Therapy refractory epilepsy Seizures within the last 2 years More than 1 anti epileptic drugs Implanted shunt system If singular primary motor cortex cannot be identified by TMS, e.g. because of bilateral cortico-spinal reorganization or resting motor threshold above 80% maximum stimulator output (MSO) Severe mental retardation Psychiatric diseases Pregnancy Uncooperative patients

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, sham-controlled, patient- and evaluator-blind, two-centre, parallel group study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Real transcranial magnetic stimulation applied | Other: Quadri-pulse theta burst stimulation<br>* High frequency transcranial quadri-pulse theta burst stimulation prior to hand motor function training<br>|
| Sham Comparator: Sahm-control<br>Sham transcranial magnetic stimulation applied | Other: Quadri-pulse theta burst stimulation<br>* High frequency transcranial quadri-pulse theta burst stimulation prior to hand motor function training<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assisting hand assessment | Difference in change of logit assisting hand assessment scores between the TMS and sham-TMS group from baseline to end of 10 days intensive hand function training. | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Corticospinal reorganization | Subgroup analyses of the primary endpoint (cortico-spinal organization, age and sex) will be computed. | 1 year | 
| Assisting hand assessement - smallest detectable difference | Number of patients per treatment group who achieved the smallest detectable difference in logit assisting hand assessment score of 5 points at visit 12. | 1 year | 
| Assisting hand assessement - Follow up | Difference in the assisting hand assessment logit score between the TMS and sham-TMS group 12 months after the standardized hand motor function training. | 1 year | 
| Neuronal plasticity | Differences in neuronal plasticity as measured by motor evoked potentials with suprathreshold TMS single pulses between baseline and visit 12 as well as after 12 months follow-up. | 1 year | 
| Box-and-blocks test | Differences of Blocks transferred with the Box-and-blocks test between the TMS and sham-TMS group between baseline and visit 12 as well as after 12 months follow-up | 1 year | 
| Goal attainment scaling | Differences in Goal Attainment Scaling between the TMS and sham-TMS group between baseline and visit 12 as well as after 12 months follow-up. | 1 year | 
| Canadian occupational performance measure | Differences in the Canadian Occupational Performance Measure scale between the TMS and sham-TMS group between baseline and visit 12 as well as after 12 months follow-up. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Unilateral Spastic Cerebral Palsy, Cortico-spinal Reorganization, Transcranial Magnetic Stimulation, Sham-controlled Trial, Intensive Hand Function Training