Thalamic stimulation to prevent impaired consciousness in epilepsy
丘脑刺激可预防癫痫意识障碍
基本信息
- 批准号:10387142
- 负责人:
- 金额:$ 227.55万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:
项目摘要
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产生重大负面影响。
后果包括发生汽车事故的风险,溺水,工作不佳和学校表现以及
社会污名化。发作/发表式唤醒受损也可能会损害呼吸,导致突然
癫痫病意外死亡。尽管癫痫护理的主要目标是停止癫痫发作,恢复
在无法停止癫痫发作的患者中有意识的意识(药物,手术或深脑
刺激)可以显着改善预后。癫痫以外的意识障碍长期很长
大脑刺激(DB)
丘脑内中央侧核(Cl)是一种恢复有意识唤醒的有前途的方法
目前正在因慢性意识疾病而受到考验(N. Schiff,Ninds UH3 NS095554)。最近的
神经影像学和脑电图研究表明,临时叶癫痫中意识的短暂性受损
(TLE)癫痫发作还取决于皮层皮层唤醒,包括丘脑CL。转化研究
我们的研究小组进一步证明了边缘癫痫发作的CL功能抑郁,最重要的是
丘脑CL刺激有可能恢复发作的生理和行为唤醒
邮政时期。癫痫的DBS治疗随着反应迅速的批准,癫痫的治疗已迅速发展
神经刺激(RN,神经胶质)和丘脑前核刺激(Medtronic)。调查
诸如RC+S(Medtronic)之类的设备为响应刺激多达4个提供了独特的机会
单独的大脑区域,使传统位点(例如海马(HC))与创新相结合
诸如丘脑CL等靶标。同时,Mayo的Worrell博士小组开发了癫痫的个人
助理设备(EPAD),一种在带双向的手持设备上运行的自定义应用程序
与RC+S的通信。 EPAD将启用基于云的数据存储,癫痫发作日记和自动
行为测试类似于我们之前已验证的行为测试。因此,我们的目标是开发和试点测试
双侧丘脑CL刺激的可行性和安全性,使用RC+S恢复有意识的唤醒
传统响应式神经刺激不会阻止的癫痫发作,从而提供了希望大大改善的癫痫发作
这些患者的生活质量。我们的目的是首先进行RC+S和
用于CL模拟的EPAD算法导致FDA IDE批准。其次,我们将启动小型临床试验
植入难治性TLE患者的RC+S,并从开放标签的HC模拟和基线开始
EPAD行为测试。第三,我们将调整唤醒的响应式丘脑CL刺激参数。
最后,我们将测试响应性CL刺激的安全性和最初的可行性,以恢复癫痫发作的唤醒。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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{{ truncateString('HAL BLUMENFELD', 18)}}的其他基金
Thalamic stimulation to prevent impaired consciousness in epilepsy
丘脑刺激可预防癫痫意识障碍
- 批准号:
10017335 - 财政年份:2019
- 资助金额:
$ 227.55万 - 项目类别:
Thalamic stimulation to prevent impaired consciousness in epilepsy
丘脑刺激可预防癫痫意识障碍
- 批准号:
10477293 - 财政年份:2019
- 资助金额:
$ 227.55万 - 项目类别:
Thalamic stimulation to prevent impaired consciousness in epilepsy
丘脑刺激可预防癫痫意识障碍
- 批准号:
9811685 - 财政年份:2019
- 资助金额:
$ 227.55万 - 项目类别:
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 - 财政年份:2019
- 资助金额:
$ 227.55万 - 项目类别:
Neuroimaging, neuronal firing and behavior in spike-wave seizures
棘波癫痫发作的神经影像学、神经元放电和行为
- 批准号:
9445655 - 财政年份:2017
- 资助金额:
$ 227.55万 - 项目类别:
Neuroimaging, neuronal firing and behavior in spike-wave seizures
棘波癫痫发作的神经影像学、神经元放电和行为
- 批准号:
10624315 - 财政年份:2017
- 资助金额:
$ 227.55万 - 项目类别:
Neuroimaging, neuronal firing and behavior in spike-wave seizures
棘波癫痫发作的神经影像学、神经元放电和行为
- 批准号:
10403184 - 财政年份:2017
- 资助金额:
$ 227.55万 - 项目类别:
Neuroimaging, neuronal firing and behavior in spike-wave seizures
棘波癫痫发作的神经影像学、神经元放电和行为
- 批准号:
10459627 - 财政年份:2017
- 资助金额:
$ 227.55万 - 项目类别:
Deep brain stimulation to prevent impaired consciousness in epilepsy
深部脑刺激可预防癫痫意识障碍
- 批准号:
8804292 - 财政年份:2014
- 资助金额:
$ 227.55万 - 项目类别:
Deep brain stimulation to prevent impaired consciousness in epilepsy
深部脑刺激可预防癫痫意识障碍
- 批准号:
8700052 - 财政年份:2014
- 资助金额:
$ 227.55万 - 项目类别:
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