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Continuous thetaburst stimulation for the treatment of refractory neocortical epilepsy

Sofie Carrette1, 2*, Debby Klooster3, 4, Willeke Staljanssens5, Pieter Van Mierlo5, Annelies Van Dycke6, Evelien Carrette1, 2, 4, Robrecht Raedt1, Alfred Meurs1, 2, Chris Baeken7, Kristl Vonck1, 2 and Paul Boon1, 2, 3
  • 1 Ghent University, Belgium
  • 2 Ghent University Hospital, Department of Neurology, Belgium
  • 3 Kempenhaeghe Academic Center for Epileptology, Heeze, the Netherlands, Netherlands
  • 4 Eindhoven University of Technology, Netherlands
  • 5 Ghent University, Belgium
  • 6 AZ Sint-Jan Brugge, Department of Neurology, Belgium
  • 7 Ghent University Hospital, Department of Psychiatry, Belgium

Aim Repetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions (1). Continuous thetaburst stimulation (TBS) seems to be a potent protocol with potential superiority compared to conventional rTMS with regards to safety, tolerability and applicability based on a lower stimulation intensity and duration. No reports of cTBS in the context of epilepsy have been published to date. Methods Patients with refractory neocortical epilepsy are treated with a 4-day open label accelerated cTBS protocol, consisting of 5 trains per day (600pulses per train, 10min intertain interval, 80% resting motor threshold), targeted over the epileptogenic focus using a navigated figure-of-8 coil. Seizure frequency and adverse events are assessed over a 4-week baseline period and 8 weeks of follow-up. Cognitive and neuropsychological testing is performed at baseline and end of follow-up. Results Four subjects completed the study protocol. Subject 1 (M, 51y) and subject 2 (M, 27y) suffer from refractory epilepsy due to a low-grade tumor in the primary motor cortex causing focal clonic motor seizures. Subject 1 also experiences myoclonia of the left leg. Subject 3 (F, 55y) suffered from an intracranial hemorrhage in the left temporal lobe and subsequently developed refractory epilepsy with focal non-motor seizures with auditory symptoms. Subject 4 (F, 50y) has focal clonic and myoclonic motor seizures of the right leg of unknown etiology. In all subjects cTBS was well-tolerated and did not induce serious adverse events or seizures. A mild headache occurred in subject 3 following 2 out of 4 sessions and responded well to treatment with first-line pain relief. No negative cognitive or psychological side effects were noticed. Anti-epileptic effects of cTBS varied. Subject 1 experienced a transient reduction in severity of clonic seizures, with complete resolution of myoclonia for a duration of 6 weeks. Subject 2 experienced an overall 50% seizure frequency reduction, with most pronounced effect during treatment and initial 4 weeks of follow-up (70% reduction, 3 seizure-free weeks). No marked effect on seizure frequency or severity could be identified in subject 3. Subject 4 presented with an overall 50% seizure frequency reduction, but did show a considerable seizure frequency variability during baseline. Conclusions The results of this pilot study show that cTBS is safe and well-tolerated in subjects intrinsically prone to seizure occurence. A reduction in seizure frequency and/or severity was identified in 3 out of 4 subjects. The extensive parenchymal defect at the target site in subject 3 may have interfered with effective stimulation.

References

1. Carrette et al. Repetitive transcranial magnetic stimulation for the treatment of refractory epilepsy. Expert Rev Neurother. 2016 Sep;16(9):1093-110.

Keywords: Epilepsy, theta burst stimulation, repetitive transcranial magnetic stimulation (rTMS), Treatment, anti-epileptic effect, Safety

Conference: 12th National Congress of the Belgian Society for Neuroscience, Gent, Belgium, 22 May - 22 May, 2017.

Presentation Type: Poster Presentation

Topic: Novel Methods and Technology Development

Citation: Carrette S, Klooster D, Staljanssens W, Van Mierlo P, Van Dycke A, Carrette E, Raedt R, Meurs A, Baeken C, Vonck K and Boon P (2019). Continuous thetaburst stimulation for the treatment of refractory neocortical epilepsy. Front. Neurosci. Conference Abstract: 12th National Congress of the Belgian Society for Neuroscience. doi: 10.3389/conf.fnins.2017.94.00073

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Received: 24 Apr 2017; Published Online: 25 Jan 2019.

* Correspondence: Miss. Sofie Carrette, Ghent University, Ghent, Belgium, sofie.carrette@ugent.be