Cathodal transcranial direct current stimulation in pediatric epileptic syndromes: mechanisms, limitations, and future research horizons.

INTRODUCTION

Drug-resistant epilepsy affects approximately 20 to 30% of children with epilepsy, with particularly devastating outcomes in developmental and epileptic encephalopathies (DEEs). Cathodal transcranial direct current stimulation (c-tDCS) has emerged as a promising noninvasive neuromodulation approach warranting systematic evaluation.

STATE OF THE ART: Recent meta-analyses of randomized controlled trials demonstrate significant reductions in seizure frequency following c-tDCS compared with sham stimulation, corresponding to roughly 3 to 4 fewer seizures per month or a proportional reduction of about 45% at 4 weeks. Evidence supports efficacy in focal epilepsies and selected syndromes, including Lennox-Gastaut syndrome and early-onset epileptic encephalopathies. Standard protocols employ 1 to 2 mA cathodal stimulation for 20 minutes over 5 to 10 consecutive sessions. High-definition tDCS configurations allow more focal current delivery. However, significant inter-individual variability exists, and the relationship between interictal epileptiform discharge suppression and clinical seizure outcomes remains inconsistent. Computational modeling demonstrates substantially higher cortical electric field strengths in children than in adults at equivalent current intensities, raising important dosing considerations. Safety data from over 600 pediatric sessions indicate favorable tolerability with no serious adverse events, although seizure exacerbation has been reported in a minority of participants in open-label studies.

CLINICAL IMPLICATIONS: Cathodal tDCS represents a safe, tolerable, and potentially effective adjunct to unchanged antiseizure medication regimens in children with drug-resistant focal epilepsy and should presently be regarded as investigational. Selection criteria, optimal stimulation parameters, and syndrome-specific protocols require further refinement. Particular caution is warranted with transcranial alternating current stimulation in generalized epilepsies.

FUTURE DIRECTIONS: Research priorities include closed-loop electroencephalography (EEG)-triggered stimulation systems, biomarker- driven patient selection, age-appropriate dosimetry informed by computational modeling, and adequately powered trials in specific DEE populations including West syndrome, Dravet syndrome, and epileptic encephalopathy with spike-wave activation during sleep.