Aim: The aim of this study was to determine the feasibility and efficacy of five treatments of 6 Hz 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 10 years 10 months, SD 2 years 10 months; 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.

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 affect 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), aged 8 to 18 years old. Exploratory analyses compared hand function measures with regard 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% CI = 9.32-33.46, P = .001). The mean difference in grip strength was −30.8 N (95% CI = −61.9 to 0.31, P = .052). Resting motor thresholds between groups were not significant, but age was significantly associated with resting motor threshold ( P < .001; P = .001). Children with UCP ipsilateral pattern of motor representation demonstrated greater mean differences between hands than children with contralateral pattern of motor representation ( P < .001). All results were 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.

The 10/20 electroencephalogram (EEG) measurements system often guides electrode placement for transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation. One targeted region of the brain is the primary motor cortex (M1) for motor recovery after stroke, among other clinical indications. M1 is identified by C3 and C4 of the 10/20 EEG system yet the reliability of 10/20 EEG measurements by novice research raters is unknown. We investigated the reliability of the 10/20 EEG measurements for C3 and C4 in 25 adult participants. Two novice raters were assessed for inter-rater reliability. Both raters received two hours of instruction from a registered neurodiagnostic technician. One of the raters completed the measurements across two testing days for intra-rater reliability. Relative reliability was determined using the intraclass coefficient (ICC) and absolute reliability. We observed a low to fair inter and intra-rater ICC for motor cortex measurements. The absolute reliability was <1.0 cm by different novice raters and on different days. Although a low error was observed, consideration of the integrity of the targeted region of the brain is critical when designing tDCS interventions in clinical populations who may have compromised brain structure, due to a lesion or altered anatomy.

To investigate the safety of combining a 6-Hz primed low-frequency repetitive transcranial magnetic stimulation (rTMS) intervention in the contralesional hemisphere with a modified constraint-induced movement therapy (mCIMT) program in children with congenital hemiparesis. Phase 1 randomized, double-blinded, placebo-controlled pretest/posttest trial. University academic facility and pediatric specialty hospital. Subjects (N = 19; age range, 8-17 y) with congenital hemiparesis caused by ischemic stroke or periventricular leukomalacia. No subject withdrew because of adverse events. All subjects included completed the study. Subjects were randomized to 1 of 2 groups: either real rTMS plus mCIMT (n = 10) or sham rTMS plus mCIMT (n = 9). Adverse events, physician assessment, ipsilateral hand function, stereognosis, cognitive function, subject report of symptoms assessment, and subject questionnaire. No major adverse events occurred. Minor adverse events were found in both groups. The most common events were headaches (real: 50%, sham: 89%; P = .14) and cast irritation (real: 30%, sham: 44%; P = .65). No differences between groups in secondary cognitive and unaffected hand motor measures were found. Primed rTMS can be used safely with mCIMT in congenital hemiparesis. We provide new information on the use of rTMS in combination with mCIMT in children. These findings could be useful in research and future clinical applications in advancing function in congenital hemiparesis.

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.