Transcranial direct current stimulation reduces seizure frequency in patients with refractory focal epilepsy: A randomized, double-blind, sham-controlled, and three-arm parallel multicenter study

Yang, Dongrui; Wang, Qun; Xu, Cuiping; Fang, Fang; Fan, Jingjing; Li, Liping; Du, Qiaoyi; Zhang, Ruihua; Wang, Ye; Lin, Yicong; Huang, Zhaoyang; Wang, Hongmei; Chen, Chunhong; Xu, Qinlan; Wang, Yue; Zhang, Yi; Zhang, Zhang; Zhao, Xin; Zhao, Xuan; Li, Ting; Liu, Chunyan; Niu, Yulian; Zhou, Qihui; Zhou, Qilin; Duan, Yiran; Liu, Xiao; Yu, Tingting; Qin, Xue; Li, Jing; Dai, Xiaona; Han, Jiaqi; Ren, Chang­hong; Xu, Huini; Li, Na; Zhang, Jishui; Xu, Na; Yang, Kun; Wang, Yuping

doi:10.1016/j.brs.2019.09.006

Cited by 82 publications

(73 citation statements)

References 45 publications

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“…Both clinical trials 33–37 and preclinical studies 3,12,38 suggest prospects for ctDCS in the treatment of epilepsy, but with incomplete seizure suppression and overall inconsistent results 39,40 such that participants remain with seizures (albeit in some trials reduced in frequency) after treatment 37 . In addition to the role of ctDCS parameters (eg, stimulation location, intensity, duration, repetition frequency), which determine clinical efficacy, 39 the inhomogeneous ctDCS aftereffects across the cortex that we demonstrate may contribute to the incomplete clinical effects in trials.…”

Section: Discussionmentioning

confidence: 99%

Drug‐Responsive Inhomogeneous Cortical Modulation by Direct Current Stimulation

Sun

Dhamne

Carretero-Guillén

et al. 2020

Annals of Neurology

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Objective Cathodal direct current stimulation (cDCS) induces long‐term depression (LTD)‐like reduction of cortical excitability (DCS‐LTD), which has been tested in the treatment of epilepsy with modest effects. In part, this may be due to variable cortical neuron orientation relative to the electric field. We tested, in vivo and in vitro, whether DCS‐LTD occurs throughout the cortical thickness, and if not, then whether drug–DCS pairing can enhance the uniformity of the cortical response and the cDCS antiepileptic effect. Methods cDCS‐mediated changes in cortical excitability were measured in vitro in mouse motor cortex (M1) and in human postoperative neocortex, in vivo in mouse somatosensory cortex (S1), and in a mouse kainic acid (KA)‐seizure model. Contributions of N‐methyl‐D‐aspartate–type glutamate receptors (NMDARs) to cDCS‐mediated plasticity were tested with application of NMDAR blockers (memantine/D‐AP5). Results cDCS reliably induced DCS‐LTD in superficial cortical layers, and a long‐term potentiation (LTP)‐like enhancement (DCS‐LTP) was recorded in deep cortical layers. Immunostaining confirmed layer‐specific increase of phospho‐S6 ribosomal protein in mouse M1. Similar nonuniform cDCS aftereffects on cortical excitability were also found in human neocortex in vitro and in S1 of alert mice in vivo. Application of memantine/D‐AP5 either produced a more uniform DCS‐LTD throughout the cortical thickness or at least abolished DCS‐LTP. Moreover, a combination of memantine and cDCS suppressed KA‐induced seizures. Interpretation cDCS aftereffects are not uniform throughout cortical layers, which may explain the incomplete cDCS clinical efficacy. NMDAR antagonists may augment cDCS efficacy in epilepsy and other disorders where regional depression of cortical excitability is desirable. ANN NEUROL 2020;88:489–502

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Section: Discussionmentioning

confidence: 99%

Drug‐Responsive Inhomogeneous Cortical Modulation by Direct Current Stimulation

Sun

Dhamne

Carretero-Guillén

et al. 2020

Annals of Neurology

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“…To date only 5 adults patients with refractory epilepsy has been reported with seizures during c-tDCS trials; two from our previous clinical trial [6] and 3 (2 seizures in the placebo arm) from Yang et al [7], In these cases, stimulation was stopped immediately without additional anti-seizure medications or special additional evaluations and the c-tDCS session was re-started the next day without any additional complications. We report three additional instances of in-session seizure during c-tDCS where a direct comparison with the patients' habitual seizure is available.…”

Section: To the Editormentioning

confidence: 99%

In-session seizures during transcranial direct current stimulation in patients with epilepsy

et al. 2021

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“…A very recent RCT aimed at the anticonvulsant effect of tDCS especially in patients with pharmacoresistant focal epilepsies (Yang et al 2020 ). The multicenter clinical trial applied different tDCS paradigms to three groups of patients.…”

Section: Introductionmentioning

confidence: 99%

“…Seizure frequency reduction in group 3 was significantly larger than in group 2. The authors concluded, that tDCS on 14 consecutive days significantly decreased seizure frequency in patients with pharmacoresistant focal epilepsies, with two daily 20 min stimulations being superior to a 20 min daily stimulation protocol (Yang et al 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…Noninvasive cathodal tDCS is suggested to provoke transient and long-term effects on cortical excitability (Antal et al 2017 ; Luu et al 2016 ; Nitsche et al 2003 ; Nitsche and Paulus 2000 ; Stagg et al 2018 ) and epileptiform discharges (Holmes et al 2019 ; VanHaerents et al 2020 ; Yang et al 2020 ). Whereas acute effects of cathodal tDCS are due to transient hyperpolarization of cortical neurons (Nitsche et al 2003 ; Nitsche and Paulus 2000 ), human experimental studies provide evidence that long-term effects base upon LTD (Stagg et al 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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Cortical stimulation in pharmacoresistant focal epilepsies

Ellrich

2020

Bioelectron Med

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Pharmacoresistance and adverse drug events designate a considerable group of patients with focal epilepsies that require alternative treatments such as neurosurgical intervention and neurostimulation. Electrical or magnetic stimulations of cortical brain areas for the treatment of pharmacoresistant focal epilepsies emerged from preclinical studies and experience through intraoperative neurophysiological monitoring in patients. Direct neurostimulation of seizure onset zones in neocortical brain areas may specifically affect neuronal networks involved in epileptiform activity without remarkable adverse influence on physiological cortical processing in immediate vicinity. Noninvasive low-frequency transcranial magnetic stimulation and cathodal transcranial direct current stimulation are suggested to be anticonvulsant; however, potential effects are ephemeral and require effect maintenance by ongoing stimulation. Invasive responsive neurostimulation, chronic subthreshold cortical stimulation, and epicranial cortical stimulation cover a broad range of different emerging technologies with intracranial and epicranial approaches that still have limited market access partly due to ongoing clinical development. Despite significant differences, the present bioelectronic technologies share common mode of actions with acute seizure termination by high-frequency stimulation and long-term depression induced by low-frequency magnetic or electrical stimulation or transcranial direct current stimulation.

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Transcranial direct current stimulation reduces seizure frequency in patients with refractory focal epilepsy: A randomized, double-blind, sham-controlled, and three-arm parallel multicenter study

Cited by 82 publications

References 45 publications

Drug‐Responsive Inhomogeneous Cortical Modulation by Direct Current Stimulation

Drug‐Responsive Inhomogeneous Cortical Modulation by Direct Current Stimulation

In-session seizures during transcranial direct current stimulation in patients with epilepsy

Cortical stimulation in pharmacoresistant focal epilepsies

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