Aim The aim of this study was to determine the feasibility and efficacy of five treatments of 6Hz primed, low-frequency, repetitive transcranial magnetic stimulation (rTMS) combined with constraint-induced movement therapy (CIMT) to promote recovery of the paretic hand in children with congenital hemiparesis. Method Nineteen children with congenital hemiparesis aged between 8 and 17 years (10 males, nine females; mean age 10y 10mo, SD 2y 10mo; Manual Ability Classification Scale levels I-III) underwent five sessions of either real rTMS (n=10) or sham rTMS (n=9) alternated daily with CIMT. CIMT consisted of 13 days of continuous long-arm casting with five skin-check sessions. Each child received a total of 10 hours of one-to-one therapy. The primary outcome measure was the Assisting Hand Assessment (AHA) and the secondary outcome variables were the Canadian Occupational Performance Measure (COPM) and stereognosis. A Wilcoxon signed-rank sum test was used to analyze differences between pre- and post-test scores within the groups. Analysis of covariance was used to compute mean differences between groups adjusting for baseline. Fisher’s exact test was used to compare individual change in AHA raw scores with the smallest detectable difference (SDD) of 4 points. Results All participants receiving treatment finished the study. Improvement in AHA differed significantly between groups (p=0.007). No significant differences in the secondary outcome measures were found. Eight out of 10 participants in the rTMS/CIMT group showed improvement greater than the SDD, but only two out of nine in the sham rTMS/CIMT group showed such improvement (p=0.023). No serious adverse events occurred. Interpretation Primed, low-frequency rTMS combined with CIMT appears to be safe, feasible, and efficacious in pediatric hemiparesis. Larger clinical trials are now indicated.

Clinicaltrials.govNCT 02250092.

Objective We investigated the preliminary efficacy of cathodal transcranial direct current stimulation (tDCS) combined with bimanual training in children and young adults with unilateral cerebral palsy based on the principle of exaggerated interhemispheric inhibition (IHI). Methods Eight participants with corticospinal tract (CST) connectivity from the lesioned hemisphere participated in an open-label study of 10 sessions of cathodal tDCS to the nonlesioned hemisphere (20 minutes) concurrently with bimanual, goal-directed training (120 minutes). We measured the frequency of adverse events and intervention efficacy with performance (bimanual—Assisting Hand Assessment (AHA)—and unimanual—Box and Blocks), self-report (Canadian Occupational Performance Measure (COPM), ABILHAND), and neurophysiologic (motor-evoked potential amplitude, cortical silent period (CSP) duration, and motor mapping) assessments. Results All participants completed the study with no serious adverse events. Three of 8 participants showed gains on the AHA, and 4 of 8 participants showed gains in Box and Blocks (more affected hand). Nonlesioned CSP duration decreased in 6 of 6 participants with analyzable data. Cortical representation of the first dorsal interosseous expanded in the nonlesioned hemisphere in 4 of 6 participants and decreased in the lesioned hemisphere in 3 of 4 participants with analyzable data. Conclusions While goal achievement was observed, objective measures of hand function showed inconsistent gains. Neurophysiologic data suggests nonlinear responses to cathodal stimulation of the nonlesioned hemisphere. Future studies examining the contributions of activity-dependent competition and cortical excitability imbalances are indicated.

Background Neurorehabilitation interventions in children with unilateral cerebral palsy (UCP) target motor abilities in daily life yet deficits in hand skills persist. Limitations in the less-affected hand may impact overall bimanual hand skills. Objective To compare hand function, by timed motor performance on the Jebsen-Taylor Test of Hand Function (JTTHF) and grip strength of children with UCP to children with typical development (CTD), ages 8–18 years old. Exploratory analyses compared hand function measures with respect to neurophysiological outcomes measured by transcranial magnetic stimulation and between group comparisons of hemispheric motor threshold. Methods Baseline hand skills were evaluated in 47 children (21 UCP; 26 CTD). Single-pulse transcranial magnetic stimulation testing assessed corticospinal tract and motor threshold. Results The mean difference of the less-affected hand of children with UCP to the dominant hand of CTD on the JTTHF was 21.4 seconds [95% Confidence Interval = 9.32, 33.46, p=0.001]. The mean difference in grip strength was −30.8 N [−61.9, 0.31, p = 0.052]. Resting motor thresholds between groups were not significant, but age was significantly associated with RMT (p<0.001; p=0.001). Children with UCP ipsilateral pattern of motor representation demonstrated greater mean differences between hands than children with contralateral pattern of motor representation (p<0.001). All results adjusted for age and sex. Conclusions The less-affected hand in children with UCP underperformed the dominant hand of CTD. Limitations were greater in children with UCP ipsilateral motor pattern. Rehabilitation in the less-affected hand may be warranted. Bilateral hand function in future studies may help identify the optimal rehabilitation and neuromodulatory intervention.

Non-invasive brain stimulation has been increasingly investigated, mainly in adults, with the aims of influencing motor recovery after stroke. However, a consensus on safety and optimal study design has not been established in pediatrics. The low incidence of reported major adverse events in adults with and without clinical conditions has expedited the exploration of NIBS in children with paralleled purposes to influence motor skill development after neurological injury. Considering developmental variability in children, with or without a neurologic diagnosis, adult dosing and protocols may not be appropriate. The purpose of this paper is to present recommendations and tools for the prevention and mitigation of adverse events (AEs) during NIBS in children with unilateral cerebral palsy (UCP). Our recommendations provide a framework for pediatric NIBS study design. The key components of this report on NIBS AEs are (a) a summary of related literature to provide the background evidence and (b) tools for anticipating and managing AEs from four international pediatric laboratories. These recommendations provide a preliminary guide for the assessment of safety and risk mitigation of NIBS in children with UCP. Consistent reporting of safety, feasibility, and tolerability will refine NIBS practice guidelines contributing to future clinical translations of NIBS.