A trial of non-invasive brain stimulation to treat patients with severe epilepsy

Transcranial magnetic stimulation will be adminstered via an air-cooled figure of eight coil connected to a commerical stimulator (Magstim Rapid Plus). This will be performed in a dedicated laboratory in the Melbourne Brain Centre, on the Austin hospital Heidelberg campus. The target of stimulation will be defined using coordinates derived from previous EEG-fMRI studies looking at peak group level activation from inter-ictal epileptiform discharges in 25 patients. Two targets will be defined for each patient (one per brain side) located in Brodmann area 9 and 46 in the region of dorsolateral prefrontal cortex. Neuronavigational software on the Brainsight (Symbiotic devices, Melbourne) will be used to display the target on patient's own MRI. Continuous theta-burst TMS will be applied to these targets., The stimulation protocol is a session of 12 spaced trains of theta-burst TMS (600 pulses per train with each train lasting 40 seconds). There will be a 5 minute rest interval between trains. Stimulation will alternate between sides (6 trains over each side). The session will last approximately an hour. Treatment will be one session a day for 5 consecutive days. Prior to the treatment phase, there will be a 4 week baseline period. During this period, participants will be asked to keep a paper seizure diary as well as undertaking a 24 hour EEG and an MRI scan. Participants will also be asked to keep their usual treatment regimen stable. The seizure diary forms will be provided to all participants to fill in. Dosage of TMS will be based off resting motor threshold (RMT), measured from EMG over the abductor pollicis brevis defined as lowest threshold to get 5 or more evoked potenials out of 10 attempts at APB. On the first day, the intensity of TMS will be set as 80% of RMT and will be increased by 5% each session as tolerated (i.e 85% of RMT on day 2, 90% of RMT on day 3, 95% of RMT at day 4 and 100% of RMT at day 5). Tolerability will be defined as absence of muscule discomfort, headache or localised pain at scalp stimulation site. If RMT is unable to be measured, then intensity will be set at 80% of maximum intensity output of the TMS machine and a similar uptitration of dosing will occur. Strategies to improve adherence will include demonstration of the devices before sessions, presence of carers/parents during sessions, distractions including toy or ipads. If a train is interrupted due to participant's moving away, the train will be repeated. Study notes will be kept during the studies including a checklist of completed sessions to measure adherence.