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.

Background- Transcranial direct current stimulation (tDCS) has been investigated mainly in adults and doses may not be appropriate in pediatric applications. In perinatal stroke where potential applications are promising, rational adaptation of dosage for children remains under investigation. Objective - Construct child-specific tDCS dosing parameters through case study within a perinatal stroke tDCS safety and feasibility trial. Methods- 10-year-old subject with a diagnosis of presumed perinatal ischemic stroke and hemiparesis was identified. T1 MRI scans used to derive computerized model for current flow and electrode positions. Workflow using modeling results and consideration of dosage in previous clinical trials was incorporated. Prior Ad hoc adult montages versus de novo optimized montages provided distinct risk benefit analysis. Approximating adult dose required consideration of changes in both peak brain current flow and distribution which further tradeoff between maximizing efficacy and adding safety factors. Electrode size, position, current intensity, compliance voltage, and duration were controlled independently in this process. Results- Brain electric fields modeled and compared to values previously predicted models. Approximating conservative brain current flow patterns and intensities used in previous adult trials for comparable indications, the optimal current intensity established was 0.7 mA for 10 minutes with a tDCS C3/C4 montage. Specifically 0.7 mA produced comparable peak brain current intensity of an average adult receiving 1.0 mA. Electrode size of 5x7 cm2 with 1.0 mA and low-voltage tDCS was employed to maximize tolerability. Safety and feasibility confirmed with subject tolerating the session well and no serious adverse events. Conclusion- Rational approaches to dose customization, with steps informed by computational modeling, may improve guidance for pediatric stroke tDCS trials.

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.