Carrette Sofie, Boon Paul, Klooster Debby, Van Dycke Annelies, Carrette Evelien, Miatton Marijke, Raedt Robrecht, Delbeke Jean, Meurs Alfred, Vonck Kristl
Department of Neurology, Institute for Neuroscience, Ghent University Hospital, Ghent, Belgium.
Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands.
Front Neurosci. 2022 Aug 17;16:885905. doi: 10.3389/fnins.2022.885905. eCollection 2022.
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.
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.
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.
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).
重复经颅磁刺激（rTMS）可能具有抗癫痫作用，尤其是在患有新皮质病变的患者中。最初的临床试验表明，癫痫发作减少效应的持续时间相对较短。在癫痫这种慢性疾病的背景下，theta爆发刺激（TBS）可能是优化治疗实用性和持久性的一种潜在解决方案，因为已证明它与更持久的后效应相关。TBS已在多种神经精神疾病中得到广泛研究，但此前尚未将治疗性TBS方案应用于癫痫患者。
我们对患有新皮质耐药性癫痫（DRE）的患者进行了一项为期4天的加速连续TBS（cTBS）治疗的前瞻性开放标签试点研究。一次治疗包括5组cTBS序列，每组由600个脉冲组成，以每200毫秒50赫兹的三联体脉冲串形式呈现，组间间隔为10分钟，使用神经导航引导的8字形线圈靶向癫痫病灶（EF）。在为期4周的基线期、1周的治疗期和7周的随访期内，分别将安全性和可行性以及癫痫发作频率作为主要和次要终点进行评估，采用不良事件记录、脑电图、认知和心理问卷以及患者和/或护理人员记录的癫痫发作日记。
7名受试者（4名男性：3名女性；中位年龄48岁，四分位间距25岁）接受了治疗方案。所有受试者均报告了不良事件，但均为轻度且短暂。在刺激期间或刺激后即刻未诱发临床或脑电图癫痫发作。治疗后认知和心理情绪状态均未发现恶化。治疗负担是可以接受的，但似乎取决于临床效果、持续效应的持续时间和刺激部位。在这个小患者队列中，每周癫痫发作频率中位数和无癫痫发作周数的比例没有显著变化。
我们报告了首例将cTBS作为新皮质DRE治疗方法的试验结果。在EF上进行为期4天的加速cTBS方案似乎是安全可行的。尽管这项开放标签试点研究的设计和样本量不足以可靠地确定治疗效果，但结果鼓励在专门的随机对照试验中进一步探索cTBS作为一种抗癫痫治疗方法以及与传统rTMS相比的潜在优化方案。（clinicaltrials.gov：NCT02635633）
