Distinct Biomarkers of ANT Stimulation and Seizure Freedom in an Epilepsy Patient with Ambulatory Hippocampal Electrocorticography.

IF 16.4 1区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Accounts of Chemical Research Pub Date : 2023-01-01 Epub Date: 2023-09-22 DOI:10.1159/000533680
Henry M Skelton, David M Brandman, Katie Bullinger, Faical Isbaine, Robert E Gross
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引用次数: 1

Abstract

Introduction: Deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) and responsive neurostimulation (RNS) of the hippocampus are the predominant approaches to brain stimulation for treating mesial temporal lobe epilepsy (MTLE). Both are similarly effective at reducing seizures in drug-resistant patients, but the underlying mechanisms are poorly understood. In rare cases where it is clinically indicated to use RNS and DBS simultaneously, ambulatory electrophysiology from RNS may provide the opportunity to measure the effects of ANT DBS in the putative seizure onset zone and identify biomarkers associated with clinical improvement. Here, one such patient became seizure free, allowing us to identify and compare the changes in hippocampal electrophysiology associated with ANT stimulation and seizure freedom.

Methods: Ambulatory electrocorticography and clinical history were retrospectively analyzed for a patient treated with RNS and DBS for MTLE. DBS artifacts were used to identify ANT stimulation periods on RNS recordings and measure peri-stimulus electrographic changes. Clinical history was used to determine the chronic electrographic changes associated with seizure freedom.

Results: ANT stimulation acutely suppressed hippocampal gamma (25-90Hz) power, with minimal theta (4-8Hz) suppression and without clear effects on seizure frequency. Eventually, the patient became seizure free alongside the emergence of chronic gamma increase and theta suppression, which started at the same time as clobazam was introduced. Both seizure freedom and the associated electrophysiology persisted after inadvertent DBS discontinuation, further implicating the clobazam relationship. Unexpectedly, RNS detections and long episodes increased, although they were not considered to be electrographic seizures, and the patient remained clinically seizure free.

Conclusion: ANT stimulation and seizure freedom were associated with distinct, dissimilar spectral changes in RNS-derived electrophysiology. The time course of these changes supported a new medication as the most likely cause of clinical improvement. Broadly, this work showcases the use of RNS recordings to interpret the effects of multimodal therapy. Specifically, it lends additional credence to hippocampal theta suppression as a biomarker previously associated with seizure reduction in RNS patients.

癫痫患者动态海马皮层电描记术中ANT刺激和癫痫发作自由度的不同生物标志物。
引言:丘脑前核(ANT)的深部脑刺激(DBS)和海马的反应性神经刺激(RNS)是治疗内侧颞叶癫痫(MTLE)的主要脑刺激方法。两者在减少耐药患者癫痫发作方面同样有效,但其潜在机制尚不清楚。在临床上表明同时使用RNS和DBS的罕见情况下,RNS的动态电生理学可以提供机会来测量ANT DBS在假定癫痫发作区的影响,并确定与临床改善相关的生物标志物。在这里,一名这样的患者没有癫痫发作,这使我们能够识别和比较与ANT刺激和癫痫发作自由相关的海马电生理学变化。方法:回顾性分析一例应用RNS和DBS治疗MTLE的患者的动态皮层电图和临床病史。DBS伪影用于识别RNS记录上的ANT刺激周期,并测量刺激周围的电图变化。临床病史用于确定与癫痫发作自由度相关的慢性电图变化。结果:ANT刺激急性抑制海马γ(25-90Hz)功率,θ(4-8Hz)抑制最小,对癫痫发作频率没有明显影响。最终,患者没有癫痫发作,同时出现了慢性伽马增加和θ抑制,这与clobazam的引入同时开始。DBS意外停药后,癫痫发作自由度和相关电生理学持续存在,进一步暗示了clobazam的关系。出乎意料的是,RNS检测和长时间发作增加,尽管它们不被认为是脑电图癫痫发作,并且患者在临床上仍然没有癫痫发作。结论:ANT刺激和癫痫发作自由度与RNS衍生的电生理学中不同的频谱变化有关。这些变化的时间进程支持了一种新的药物作为临床改善的最可能原因。从广义上讲,这项工作展示了使用RNS记录来解释多模式治疗的效果。具体来说,它为海马θ抑制提供了额外的证据,作为一种先前与RNS患者癫痫发作减少相关的生物标志物。
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来源期刊
Accounts of Chemical Research
Accounts of Chemical Research 化学-化学综合
CiteScore
31.40
自引率
1.10%
发文量
312
审稿时长
2 months
期刊介绍: Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.
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