Theta burst transcranial magnetic stimulation to induce seizures in an epilepsy monitoring unit

Epilepsy is a common neurological disorder affecting about 1% of the population [1]. Although medications effectively control seizures in many patients, 20e40% of patients are refractory to antiepileptic medications [2]. Many such medically intractable patients may benefit from surgical removal of an accurately identified epileptic focus [3]. The efficacy of epilepsy surgery depends on the precise localization of the epileptic focus [4], and for this patients are typically admitted to an epilepsy monitoring unit (EMU) for continuous video-EEG recording. EMU length of stay depends on the number of seizures recorded and may extend more than aweek in many cases [5], with the failure to record a sufficient number of seizures being the leading cause of prolonged EMU stay [6]. Considerable waiting lists for EMU admissions imply that reducing average EMU length of stay could have major benefits in overall patient care. Typically, hastening seizure occurrence in an EMU relies mainly on tapering anti-epileptic medications [7], and, to a lesser extent, on non-invasive measures such as sleep deprivation, hyperventilation or photic stimulation [8]. Another non-invasive method, transcranial magnetic stimulation (TMS), can be used to increase cortical excitability [9] and thus could potentially be used to purposefully induce seizures in patients with epilepsy, although TMS has not been studied for this purpose. By increasing cortical excitability, TMS could trigger seizures in an epileptic focus [10,11]. High frequency bursts of TMS known as theta burst stimulation (TBS) are known to alter cortical excitability in such a way that continuous TBS (cTBS) decreases cortical excitability whereas intermittent TBS (iTBS) increases cortical excitability [12]. Seizure induction with cTBS has been reported in a healthy subject without risk factors for epilepsy [13], and in a study of 18 healthy individuals cTBS applied to the right operculo-insular cortex was reported to induce one confirmed generalized seizure and one suspected partial seizure [14]. However, this protocol has not been studied in patients with epilepsy to induce seizures. Hence, we investigated the effects of cTBS as well as iTBS in patients during their EMU stay with the objective of determining whether seizures could be reliably induced using TBS protocols. The study was carried out in the EMU of the Toronto Western Hospital. The University Health Network (UHN) Research Ethics board (REB) approved the study (UHN REB 13-7224-B). Seven patients undergoing video-EEG recording in the EMU with presumptive localization of a single principal epileptic focus (based on history and EEG recordings) were recruited. The patients were admitted to the EMU to capture seizures as part of their routine