Randomized crossover sham-controlled clinical trial of targeted low-frequency transcranial magnetic stimulation comparing a figure-8 and a round coil to treat refractory neocortical epilepsy

Objective: Determine the efficacy and side effects of low-frequency repetitive transcranial magnetic stimulation (rTMS) to treat refractory neocortical epilepsy and study differences in effect between a figure-8 and round coil type. Methods: This single-center randomized sham-controlled crossover trial (NCT01745952 on ClinicalTrials.gov) included 11 patients with well-defined focal epilepsy. rTMS (0.5 Hz) was targeted to the focus during three treatment conditions consisting of 1,500 stimulations/day for 10 weekdays at 90% of resting motor threshold (rMT) followed by a 10-week observation period. Patients were randomized for the order in which the figure-8, round, and sham coil were used. Outcome assessors and patients were blinded to the type of coil used. The primary outcome measure was the percentage of seizure reduction after active rTMS treatment. Other outcome measures were responder rate, quality of life, and side effects. Results: There was no difference between a figure-8 and round coil. None of the patients achieved an overall 50% seizure reduction. One patient responded during 1 month after treatment with either active coil, followed by a significant increase in seizure frequency. Another patient had a fourfold increase in seizure frequency during rTMS treatment. Significance: This study provides evidence that rTMS is on average not effective for reducing seizure frequency. No difference in effectiveness between the different coil types was observed. It can, however, exacerbate seizures during treatment and lead to a rebound in seizure frequency after an initial reduction.