TMS: A Tailored Method of Stimulation for Refractory Focal Epilepsy?

Commentary Neurostimulation-based treatments for epilepsy are an alternative for the many patients who remain refractory to standard antiepileptic drugs (AEDs), but modalities such as vagus nerve stimulation, deep brain stimulation, and responsive neurostimulation require surgical implantation of hardware and are accompanied by attendant risks (1). Transcranial magnetic stimulation (TMS), by contrast, is a noninvasive painless method of modulating cortical function, which requires no surgical intervention, is safely repeatable, and can be applied to multiple different targets in the same individual. TMS has quickly attained an important role as a research tool in clinical neuroscience owing to its ability to both probe and modulate cortical physiology and has an FDA-approved clinical indication in the treatment of refractory major depression (2). The potential therapeutic effect of TMS on focal epilepsy, however, has been much less clear. Controlled clinical trials of low-frequency repetitive TMS (rTMS) in refractory epilepsy patients have yielded disparate outcomes, with seizures and interictal epileptiform discharges (IEDs) reduced in some studies but not in others (3–5). Differences in subject selection, location of TMS target, and stimulation parameters could all potentially have played a role in the variability of outcomes. The question remains: Is there a population of refractory epilepsy patients for whom low-frequency rTMS could be a useful therapeutic option? The recent report by Sun and colleagues from Beijing provides quite striking results from what appears to be the largest controlled clinical study to date of low-frequency rTMS in epilepsy. The investigators randomized 60 patients (mostly adolescents and young adults) with refractory focal epilepsy (mostly extratemporal in origin) to receive either high-intensity 0.5-Hz rTMS treatment (delivered at 90% of the resting motor threshold) or low-intensity treatment (20% of motor threshold) for 2 weeks, using a paradigm totaling 1,500 pulses of stimulation delivered each day. Outcomes included seizure frequency, IED frequency as measured on routine EEG, and scores on a psychologic symptom checklist. The results, frankly, are startlingly positive. The high-intensity treatment group had an approximately 80% reduction in seizure frequency during the 8 weeks of follow-up following the 2-week treatment period, and this magnitude of improvement was achieved quite quickly and remained remarkably steady during the follow-up period. A surprising 35% of these patients, who on average had been having nearly nine seizures per week during the baseline period, became seizure-free for the entire follow-up period. The median time to first seizure was more than 6 weeks for the high-intensity treatment group. The comparison group with low-intensity treatment, meanwhile, had no significant change in their seizure frequency following rTMS, included no subjects who became seizure-free, and had a median time of 1 week to first seizure. Low-Frequency Repetitive Transcranial Magnetic Stimulation for the Treatment of Refractory Partial Epilepsy: A Controlled Clinical Study.