Safety and tolerability of transcranial magnetic and direct current stimulation in children: Prospective single center evidence from 3.5 million stimulations

Abstract

Background: Non-invasive brain stimulation is being increasingly used to interrogate neurophysiology and modulate brain function. Despite the high scientific and therapeutic potential of non-invasive brain stimulation, experience in the developing brain has been limited. Objective: To determine the safety and tolerability of non-invasive neurostimulation in children across diverse modalities of stimulation and pediatric populations. Methods: A non-invasive brain stimulation program was established in 2008 at our pediatric, academic institution. Multi-disciplinary neurophysiological studies included single-and paired-pulse Transcranial Magnetic Stimulation (TMS) methods. Motor mapping employed robotic TMS. Interventional trials included repetitive TMS (rTMS) and transcranial direct current stimulation (tDCS). Standardized safety and tolerability measures were completed prospectively by all participants. Results: Over 10 years, 384 children underwent brain stimulation (median 13 years, range 0.8e18.0). Populations included typical development (n ¼ 118), perinatal stroke/cerebral palsy (n ¼ 101), mild traumatic brain injury (n ¼ 121) neuropsychiatric disorders (n ¼ 37), and other (n ¼ 7). No serious adverse events occurred. Drop-outs were rare (<1%). No seizures were reported despite >100 participants having brain injuries and/or epilepsy. Tolerability between single and paired-pulse TMS (542340 stimulations) and rTMS (3.0 million stimulations) was comparable and favourable. TMS-related headache was more common in perinatal stroke (40%) than healthy participants (13%) but was mild and self-limiting. Tolerability improved over time with side-effect frequency decreasing by >50%. Robotic TMS motor mapping was well-tolerated though neck pain was more common than with manual TMS (33% vs 3%). Across 612 tDCS sessions including 92 children, tolerability was favourable with mild itching/tingling reported in 37%. Conclusions: Standard non-invasive brain stimulation paradigms are safe and well-tolerated in children and should be considered minimal risk. Advancement of applications in the developing brain are warranted. A new and improved pediatric NIBS safety and tolerability form is included.

Age as a Mediator of tDCS Effects on Pain: An Integrative Systematic Review and Meta-Analysis

“…These findings are supported by an extensive literature that has presented the adverse effects of most incidents in children and adolescents frequently classified as mild, such as itching, tingling, and headaches (Krishnan et al, 2015;Moliadze et al, 2015;Ciechanski and Kirton, 2017). Also, a recent study with more than 600 tDCS sessions on children and adolescents did not find severe adverse effects, being tingling and itching the most common adverse effects reported in 37% of tDCS sessions (Zewdie et al, 2020).…”

Modulation of solute diffusivity in brain tissue as a novel mechanism of transcranial direct current stimulation (tDCS)

“…genetic modification). In contrast, tDCS is safe 2 , 62 , 63 and broadly used even on healthy subjects 64 , 65 .…”

Systematic Review on the Safety and Tolerability of Transcranial Direct Current Stimulation in Children and Adolescents

“…In the last 14 years, there have been a few very important safety reviews for tDCS in adults [2,3,5,6] and children [5,7,19]. The first from Poriesz et al [2] in 2007 reported the frequency of side effects during and after tDCS in 102 participants across 567 sessions and demonstrated that tDCS is only associated with very minor side effects such as scalp tingling (70.6%), itching (30.4%), and fatigue (35.3%).…”