Thalamic stimulation to prevent impaired consciousness in epilepsy

丘脑刺激可预防癫痫意识障碍

• 批准号: 10686272
• 负责人: HAL BLUMENFELD
• 金额: $ 130.22万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-15 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10686272
• 关键词: Adverse effects; Algorithms; Anterior Nuclear Group; Area; Arousal; Awareness; Behavioral; Bilateral; Brain region; Breathing; Caring; Central Lateral Nucleus; Chronic Disease; Clinical Trials; Communication; Conscious; Consciousness Disorders; Custom; Data; Data Storage and Retrieval; Databases; Deep Brain Stimulation; Depressed mood; Detection; Devices; Drowning; Electroencephalography; Electrophysiology (science); Eligibility Determination; Enrollment; Epilepsy; Feasibility Studies; Functional disorder; Goals; Hippocampus; Impairment; Implant; Inpatients; Institutional Review Boards; Monitor; National Institute of Neurological Disorders and Stroke; Operative Surgical Procedures; Outpatients; Patients; Performance; Persons; Pharmaceutical Preparations; Phase; Physiological; Polysomnography; Preclinical Testing; Quality of life; Randomized; Refractory; Research; Risk; Running; Schools; Seizures; Site; Specificity; Stigmatization; Stimulus; Temporal Lobe; Temporal Lobe Epilepsy; Testing; Thalamic structure; Therapeutic; Titrations; Work; behavior test; cloud based; conventional therapy; data streams; detector; diaries; handheld equipment; improved; improved outcome; innovation; neuroimaging; open label; pilot test; pre-clinical; prevent; primary outcome; safety and feasibility; safety testing; secondary outcome; social; sudden unexpected death in epilepsy; translational study; vehicular accident; verification and validation

PROJECT SUMMARY / ABSTRACT Impaired consciousness during seizures has a major negative impact on quality of life for people with epilepsy. Consequences include risk of motor vehicle accidents, drowning, poor work and school performance, and social stigmatization. Impaired ictal/postictal arousal may also compromise breathing leading to sudden unexpected death in epilepsy. Although the primary goal of epilepsy care is to stop seizures, restoring conscious awareness in patients whose seizures cannot be stopped (by medications, surgery or deep brain stimulation) could significantly improve outcome. Disorders of consciousness other than epilepsy have long been known to arise from dysfunction of subcortical-cortical arousal circuits. Deep brain stimulation (DBS) of the thalamic intralaminar central lateral nuclei (CL) is a promising approach to restore conscious arousal currently being trialed for chronic disorders of consciousness (N. Schiff, NINDS UH3 NS095554). Recent neuroimaging and EEG studies have shown that transient impaired consciousness in temporal lobe epilepsy (TLE) seizures also depends on subcortical-cortical arousal including thalamic CL. Translational studies from our research group further demonstrate depressed CL function in limbic seizures, and most importantly that thalamic CL stimulation has the potential to restore physiological and behavioral arousal in the ictal and postictal periods. DBS treatment of epilepsy has advanced rapidly with FDA approval of responsive neurostimulation (RNS, NeuroPace) and thalamic anterior nucleus stimulation (Medtronic). Investigational devices such as the RC+S (Medtronic) provide a unique opportunity for responsive stimulation of up to 4 separate brain regions, enabling conventional sites such as hippocampus (HC) to be combined with innovative targets such as thalamic CL. Meanwhile, Dr. Worrell’s group at Mayo has developed the Epilepsy Personal Assistant Device (EPAD), a custom application running on a hand-held device with bi-directional communication with the RC+S. The EPAD will enable cloud-based data storage, seizure diaries, and automatic behavioral tests similar to those we have validated previously. Therefore, our goal is to develop and pilot test the feasibility and safety of bilateral thalamic CL stimulation using RC+S to restore conscious arousal in TLE seizures which are not stopped by conventional responsive neurostimulation, offering hope to greatly improve quality of life in these patients. Our aims are to first conduct final benchtop preclinical verification of RC+S and EPAD algorithms for CL stimulation leading to FDA IDE approval. Second, we will initiate a small clinical trial implanting RC+S in patients with refractory TLE and beginning with open-label HC stimulation and baseline EPAD behavioral testing. Third, we will adjust responsive thalamic CL stimulation parameters for arousal. Finally, we will test safety and initial feasibility of responsive CL stimulation to restore arousal during seizures.

项目摘要/摘要 癫痫发作期间意识受损对癫痫患者的生活质量有重大的负面影响。 后果包括机动车事故、溺水、糟糕的工作和学业表现，以及 社会污名化。发作/发作后觉醒受损也可能影响呼吸，导致突然 因癫痫而意外死亡。虽然癫痫护理的主要目标是阻止癫痫发作，但恢复 癫痫发作无法(通过药物、手术或脑深部)停止的患者的意识觉醒 刺激)可以显著改善结果。除癫痫以外的意识障碍有很长时间 已知由皮质下-皮质唤醒回路功能障碍引起。脑深部刺激(DBS) 丘脑层内中央外侧核(CL)是恢复意识觉醒的一种有前途的方法 目前正在接受慢性意识障碍的试验(N.Schiff，NINDS UH3 NS095554)。近期 神经成像和EEG研究表明，颞叶癫痫患者的一过性意识障碍 (TLE)癫痫发作也依赖于皮质下-皮质唤醒，包括丘脑CL。翻译研究来自 我们的研究小组进一步证明了边缘癫痫的CL功能受抑，最重要的是 丘脑CL刺激有可能恢复发作期和发作期的生理和行为觉醒。 后遗症。DBS治疗癫痫进展迅速，FDA批准了Response 神经刺激(RNS，NeuroPace)和丘脑前核刺激(Medtronic)。调查性的 RC+S(美敦力)等设备为响应刺激提供了独特的机会，最高可达4 分离的大脑区域，使海马体(HC)等传统部位能够与创新的 丘脑CL等靶点。与此同时，梅奥的沃瑞尔博士的团队已经开发出了癫痫患者 助理设备(EPAD)，在手持设备上运行的定制应用程序，具有双向 与RC+S通信。EPAD将支持基于云的数据存储、癫痫日记和自动 类似于我们之前验证过的行为测试。因此，我们的目标是开发和试运行 RC+S刺激双侧丘脑CL恢复TLE意识觉醒的可行性和安全性 常规反应性神经刺激无法阻止的癫痫发作，提供了极大改善的希望 这些患者的生活质量。我们的目标是首先进行RC+S的最终台式临床前验证，并 用于CL刺激的ePad算法获得FDA IDE批准。第二，我们将启动一项小型临床试验 RC+S植入治疗难治性TLE患者，以开放标记HC刺激和基线开始 EPad行为测试。第三，我们将调整反应丘脑CL刺激参数，以唤醒。 最后，我们将测试反应性CL刺激在癫痫发作期间恢复觉醒的安全性和初步可行性。

项目成果

Evaluating consciousness and awareness during focal seizures: responsiveness testing versus recall testing.

评估局灶性癫痫发作期间的意识和意识：反应性测试与回忆测试。

• DOI: 10.1684/epd.2022.1472
• 发表时间: 2022
• 期刊: Epileptic disorders : international epilepsy journal with videotape
• 作者: ContrerasRamirez,Violeta;PatedakisLitvinov,Bogdan;Gunawardane,NisaliAnuradha;Zhao,CharlieW;Yotter,Courtney;Quraishi,ImranH;Blumenfeld,Hal
• 通讯作者: Blumenfeld,Hal