Bursts of high-frequency repetitive transcranial magnetic stimulation (rTMS), together with lorazepam, suppress seizures in a rat kainate status epilepticus model.

Abstract

Status epilepticus (SE) is a condition of prolonged or recurrent and often drug-resistant seizures where nonsedating SE therapy remains an important unmet need. Repetitive transcranial magnetic stimulation (rTMS) is emerging as a means to suppress seizures but has not been extensively studied in models. We aimed to test the antiepileptic potential of high-frequency rTMS in SE. As a step toward eventual coupling of rTMS with antiepileptic pharmacotherapy, we also tested whether high-frequency rTMS in combination with a low (ineffective but less likely to cause a side effect) lorazepam dose is as effective as a full lorazepam dose in suppressing seizures in a rat SE model. EEG was recorded to measure epileptic spike frequency in the rat kainate SE model. Epileptic spikes were counted before, during, and after either high-frequency rTMS treatment alone or high-frequency rTMS treatment in combination with lorazepam, a firstline SE treatment. We found that rTMS alone decreases epileptic spike frequency only acutely. However, combinatory treatment with half-dose lorazepam together with rTMS was as effective as a full lorazepam dose. We report that high-frequency rTMS has modest antiepileptic potential alone but acts in complement with lorazepam to suppress seizures.