Abstracts

Rationale: Repetitive transcranial magnetic stimulation (rTMS) is an established non-invasive neurostimulation technique that is able to induce neuromodulatory effects. The disturbance in cortical excitability in epilepsy provides a rationale for investigating the efficacy of rTMS as an anti-epileptic treatment. Low-frequency rTMS has shown moderate efficacy, especially in patients with neocortical lesions (1). Thetaburst stimulation (TBS) is a more recently developed rTMS protocol known to reduce cortical excitability (2). The lower stimulation intensity and number of pulses compared to conventional rTMS may imply superiority with regards to safety and applicability in the clinical setting. Methods: An open label pilot study with continuous TBS (cTBS) is currently ongoing at the Ghent University Hospital, Belgium, including refractory epilepsy patients with a well-defined superficial epileptogenic focus (EF). Treatment consists of a 4-day cTBS stimulation protocol (5 consecutive trains, 10 minutes intertrain interval, 600 pulses/train, 80% resting motor threshold) targeting the EF with a figure-of-8 coil using online neuronavigation. Seizure frequency and adverse events are assessed over a 4-week baseline period (BL), a 1-week treatment period and an 8-week follow-up period (FU). Cognitive and neuropsychological testing is performed at baseline and at maximum follow-up. Results: Two subjects have completed the study protocol. Subject 1 is a 51-year old male with refractory epilepsy due to an oligodendroglioma (WHO II) in the right paramedian rolandic area. He experiences focal motor seizures of the left leg without impairment of consciousness, with either initial dystonic posturing, clonic jerks and post-ictal paresis (3/BL) or myoclonus, spontaneous and reflex-induced, (12/BL). In the first week following cTBS, the patient experienced for the first time ever isolated auras of a descending sensation towards the left leg. During follow-up frequency of the clonic motor seizures was unchanged (6/FU), but the patient reported diminished seizure severity with regards to duration, jerking intensity and paresis. This effect gradually returned to baseline over the course of 8 weeks. Myoclonic seizures were completely suppressed for a duration of 6 weeks. Subject 2 is a 26-year old male with refractory epilepsy due to a low-grade fibrillary astrocytoma central in the left peri-rolandic area, suffering from frequent focal motor seizures of variable severity, with jerking of the right truncal muscles, spreading to the right hemisoma (16/BL). During the treatment week the subject remained seizure-free. He reported 5 seizures during the first 4 weeks of follow-up, including 2 seizure-free weeks. Subsequently, 10 seizures occurred over the second 4 follow-up weeks, with in total a 50% seizure frequency reduction over FU (15/FU). There was no marked effect on seizure severity. Treatment was well-tolerated in both subjects and did not induce seizures. Cognitive assessment, by means of the Montreal Cognitive Assessment scale, and neurospychological testing for quality of life, depression, anxiety, affect and general well-being remained stable throughout the study. Conclusions: The preliminary results of this pilot trial are in favor of safety and potential anti-epileptic effects of cTBS in patients with refractory unifocal neocortical epilepsy. Both patients experienced a period of diminished seizure frequency, for a duration of 4 to 6 weeks following a cTBS treatment protocol, and tolerated the treatment well. Funding: Sofie Carrette is supported by a grant from the "Fonds voor Wetenschappelijk Onderzoek" (FWO) Flanders.