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. 2022 Aug 17:16:885905.
doi: 10.3389/fnins.2022.885905. eCollection 2022.

Continuous theta burst stimulation for drug-resistant epilepsy

Sofie Carrette  1 , Paul Boon  1   2 , Debby Klooster  1   2 , Annelies Van Dycke  3 , Evelien Carrette  1   2 , Marijke Miatton  1 , Robrecht Raedt  1 , Jean Delbeke  1 , Alfred Meurs  1 , Kristl Vonck  1
Affiliations

Continuous theta burst stimulation for drug-resistant epilepsy

Sofie Carrette et al. Front Neurosci. .

Abstract

Introduction: Repetitive transcranial magnetic stimulation (rTMS) may have anti-epileptic effects, especially in patients with neocortical lesions. Initial clinical trials demonstrated that the duration of the seizure reducing effect is relatively short-lived. In the context of a chronic condition like epilepsy, theta burst stimulation (TBS) may represent a potential solution in optimizing treatment practicality and durability as it was demonstrated to be associated with longer-lasting after-effects. TBS has been studied extensively in diverse neuropsychiatric conditions, but a therapeutic TBS protocol has not previously been applied in epilepsy patients.

Materials and methods: We performed a prospective open-label pilot study of 4-day accelerated continuous TBS (cTBS) treatment in patients with neocortical drug-resistant epilepsy (DRE). A treatment session consisted of 5 cTBS trains, each comprising 600 pulses presented in 50 Hz triplet bursts every 200 ms, delivered at 10-min intertrain-intervals, targeted over the epileptic focus (EF) using a neuronavigation-guided figure-of-8 coil. Safety and feasibility, and seizure frequency were assessed as primary and secondary endpoints, respectively, over a 4-week baseline period, a 1-week treatment period and a 7-week follow-up period, using adverse event logging, electro-encephalography, cognitive, and psychological questionnaires and a seizure diary kept by the patients and/or caregivers.

Results: Seven subjects (4M:3F; median age 48, interquartile ranges 25) underwent the treatment protocol. Adverse events were reported in all subjects but were mild and transient. No clinical or electrographic seizures were evoked during or immediately following stimulation. No deterioration was found in cognition nor in psycho-emotional well-being following treatment. Treatment burden was acceptable, but seems to depend on clinical effect, duration of ongoing effect and stimulation site. Median weekly seizure frequency and ratio of seizure-free weeks did not change significantly in this small patient cohort.

Conclusion: We report the results of the first ever trial of cTBS as a treatment for neocortical DRE. A 4-day accelerated cTBS protocol over the EF appears safe and feasible. Although the design and sample size of this open-label pilot study is unfit to reliably identify a therapeutic effect, results encourage further exploration of cTBS as an anti-epileptic treatment and potential optimization compared to conventional rTMS in a dedicated randomized controlled trial. (clinicaltrials.gov: NCT02635633).

Keywords: epilepsy; neurostimulation; safety; theta burst stimulation; transcranial magnetic stimulation (repetitive); treatment.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared committee, MORE (The Medtronic Registry for Epilepsy), with one of the author, PB, at the time of review.

Figures

FIGURE 1
FIGURE 1
Overview of study design. cTBS, continuous theta burst stimulation; EEG, electroencephalography; MoCA, Montreal Cognitive assessment; CVST, comuterized visual searching task; QOLIE-31, quality of life in epilepsy-31; BDI-II, Beck depression inventory version II; STAI, state-trait anxiety inventory; PANAS, positive affect negative affect scale; VAS, visual analogue scale.
FIGURE 2
FIGURE 2
Visual representation of treatment burden perceived by the participants.
FIGURE 3
FIGURE 3
Visual representation of weekly seizure frequency. Colored lines represent weekly seizure frequency per subject. Bold dotted line represents the median group value.
FIGURE 4
FIGURE 4
Stimulation target in subject 7.
See this image and copyright information in PMC

References

    1. Awiszus F. (2003). TMS and threshold hunting. Suppl. Clin. Neurophysiol. 56 13–23. 10.1016/S1567-424X(09)70205-3 - DOI - PubMed
    1. Barker A. T. (2002). The History and Basic Principles of Magnetic Nerve Stimulation. Handbook of Transcranial Magnetic Stimulation. London: Arnold
    1. Barker A. T., Jalinous R., Freeston I. L. (1985). Non-invasive magnetic stimulation of human motor cortex. Lancet 1 1106–1107. 10.1016/S0140-6736(85)92413-4 - DOI - PubMed
    1. Cole E. J., Phillips A. L., Bentzley B. S., Stimpson K. H., Nejad R., Barmak F., et al. (2022). Stanford Neuromodulation Therapy (SNT): a Double-Blind Randomized Controlled Trial. Am. J. Psychiatry 179 132–141. 10.1176/appi.ajp.2021.20101429 - DOI - PubMed
    1. Cole E. J., Stimpson K. H., Bentzley B. S., Gulser M., Cherian K., Tischler C. (2020). Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. Am. J. Psychiatry 177 716–726. 10.1176/appi.ajp.2019.19070720 - DOI - PubMed

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