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

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

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

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.

Unilateral Spastic Cerebral Palsy, Cortico-spinal Reorganization, Transcranial Magnetic Stimulation, Sham-controlled Trial, Intensive Hand Function Training

High frequency transcranial quadri-pulse theta burst stimulation prior to hand motor function training

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.

Subgroup analyses of the primary endpoint (cortico-spinal organization, age and sex) will be computed.

Number of patients per treatment group who achieved the smallest detectable difference in logit assisting hand assessment score of 5 points at visit 12.

Difference in the assisting hand assessment logit score between the TMS and sham-TMS group 12 months after the standardized hand motor function training.

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.

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

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.

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.

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

Clinic for Neuropediatrics and Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik