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: Transcranial direct current stimulation (tDCS) is a form of noninvasive brain stimulation that has shown improved adult stroke outcomes. Applying tDCS in children with congenital hemiparesis has not yet been explored. Objective: The primary objective of this study was to explore the safety and feasibility of single-session tDCS through an adverse events profile and symptom assessment within a double-blind, randomized placebo-controlled preliminary study in children with congenital hemiparesis. A secondary objective was to assess the stability of hand and cognitive function. Design: A double-blind, randomized placebo-controlled pretest/posttest/follow-up study was conducted. Setting: The study was conducted in a university pediatric research laboratory. Participants: Thirteen children, ages 7 to 18 years, with congenital hemiparesis participated. Measurements: Adverse events/safety assessment and hand function were measured. Intervention: Participants were randomly assigned to either an intervention group or a control group, with safety and functional assessments at pretest, at posttest on the same day, and at a 1-week follow-up session. An intervention of 10 minutes of 0.7 mA tDCS was applied to bilateral primary motor cortices. The tDCS intervention was considered safe if there was no individual decline of 25% or group decline of 2 standard deviations for motor evoked potentials (MEPs) and behavioral data and no report of adverse events. Results: No major adverse events were found, including no seizures. Two participants did not complete the study due to lack of MEP and discomfort. For the 11 participants who completed the study, group differences in MEPs and behavioral data did not exceed 2 standard deviations in those who received the tDCS (n=5) and those in the control group (n=6). The study was completed without the need for stopping per medical monitor and biostatisticial analysis. Limitations: A limitation of the study was the small sample size, with data available for 11 participants. Conclusions: Based on the results of this study, tDCS appears to be safe, feasible, and well tolerated in most children with hemiparesis. Future investigations of serial sessions of tDCS in conjunction with rehabilitation in pediatric hemiparesis are indicated to explore the benefit of a synergistic approach to improving hand function.

Rett syndrome is a genetically based neurodevelopmental disorder. Although the clinical consequences of Rett syndrome are profound and lifelong, currently no approved drug treatments are available specifically targeted to Rett symptoms. High quality outcome measures, specific to the core symptoms of a disorder are a critical component of well-designed clinical trials for individuals with neurodevelopmental disorders. The Clinical Global Impression Scale is a measure of global clinical change with strong face validity that has been widely used as an outcome measure in clinical trials of central nervous system disorders. Despite its favorable assay sensitivity in clinical trials, as a global measure, the Clinical Global Impression Scale is not specific to the signs and symptoms of the disorder under study. Development of key anchors for the scale, specific to the disorder being assessed, holds promise for enhancing the validity and reliability of the measure for disorders such as Rett syndrome.