Defining the Epileptogenic Network and Identifying which Components Generate Seizures
Defining the Epileptogenic Network and Identifying which Components Generate Seizures
批准号:
9792287
负责人:
Richard Staba
金额:
$54.58万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-09-30 至 2023-05-31
关键词:
AddressAffectAreaBilateralBrainBrain regionCaringChronicComorbidityCouplingDataDiagnosisDiagnosticDiffusion Magnetic Resonance ImagingDrug resistanceElectrodesElectroencephalographyEpilepsyEtiologyEventExcisionFailureFiberFreedomGenerationsHigh Frequency OscillationHippocampus (Brain)HistopathologyIndividualKnowledgeLearningLesionMagnetic Resonance ImagingMeasuresMorphologyNeocortexNeuropsychologyObservational StudyOperative Surgical ProceduresOutcomePartial EpilepsiesPathologyPathway interactionsPatientsPatternPharmacotherapyPlayPositron-Emission TomographyPropertyResearchRiskRoleScalp structureSeizuresSiteSpatial DistributionStructural defectStructureSurgically-Created Resection CavityTemporal LobeTemporal Lobe EpilepsyTestingTissuesWhite FiberWorkbrain abnormalitiescell typeclinical careeffective therapygray matterhippocampal sclerosisimprovedinterestmortalitymortality riskneocorticalnervous system disordernovelnovel strategiesnovel therapeuticsoutcome forecastpotential biomarkerpublic health relevancewhite matterwhite matter change
中文摘要
项目摘要
癫痫是一种严重的神经系统疾病,其特征是自发性癫痫发作并增加发病风险。
死亡率,特别是对三分之一患有慢性癫痫的人来说,尽管有这种情况,但无法控制
最佳药物疗法。目前,对耐药癫痫最有效的治疗方法是切除手术。
在颞叶癫痫(TLE)合并海马体硬化的情况下,最常见的药物形式-
难治性癫痫,手术可以减少或消除大多数患者的癫痫发作。然而,这并不能帮助所有人。
患者,特别是那些怀疑癫痫发作始于颞叶但没有MRI损害或
MRI显示双侧海马区和新皮质或头皮病变。在这样的情况下
致痫区域(EZ)的范围,这是大脑产生癫痫的必要和充分的区域
癫痫发作和缓解癫痫所需的最小切除,是不确定的。人们对…有极大的兴趣
对致痫网络(EN)的研究,即支持癫痫的产生和传播的较大脑区
发作和癫痫的表现,我们假设在疑难的TLE病例中,对En的了解
可以帮助我们确定EZ的位置。尽管最近对EN的研究取得了进展,但我们仍然不知道全部情况
定义脑电的大脑异常程度,哪些部分是产生癫痫所必需的,或者有多少
需要取出EN以消除癫痫发作。这个项目解决了这些问题,我们开发了一种
研究它们的综合方法,包括新的结构和扩散磁共振成像和脑电功能
连通性测试,以及对高频振荡(HFO)的研究,这是一种潜在的
EZ。我们将把这种方法应用于怀疑患有TLE的手术前患者,他们需要进行有创性的脑电测试。
作为他们标准诊断护理的一部分。为了帮助我们在目标1中定义EN,我们将评估结构MRI
脑区之间的灰质异常和形态协方差;在目标2中,我们将评估
脑白质微结构和纤维束异常的弥散磁共振成像;在目标3中,我们将使用一种新的方法
称为伽马事件耦合,结合单位和HFO记录来研究功能
包括EN的连通性,并确定它的哪些部分正在产生癫痫发作和传播;最后
在目标4中,我们将确定EN的哪些组件以及需要移除多少组件才能消除
癫痫发作。在本项目中,定义EN应提供有关结构和
产生癫痫的功能机制,最终这将帮助我们定位EZ,改善
诊断,推进手术和非手术治疗,开发新的治疗方法,并增加
抽搐自由。
英文摘要
Project Summary
Epilepsy is a serious neurological disorder characterized by spontaneous seizures and increased risk of
mortality, especially for one-third of the individuals with chronic seizures that cannot be controlled in spite of
optimal drug therapy. Currently, the most effective treatment for drug-resistant seizures is resective surgery
and in cases such as temporal lobe epilepsy (TLE) with hippocampal sclerosis, the most common form of drug-
resistant epilepsy, surgery can reduce or eliminate seizures in most patients. However, it does not help all
patients, particularly those with seizures suspected to begin in the temporal lobe but without a MRI lesion or
MRI contains a lesion in hippocampus and neocortex or scalp EEG indicates bilaterally. In situations like these
the extent of the epileptogenic zone (EZ), which is the brain area that is necessary and sufficient for generating
seizures and minimum resection necessary for seizure relief, is uncertain. There is tremendous interest in
studies of the epileptogenic network (EN), i.e. the larger brain region that supports the generation and spread
of seizures and manifestation of epilepsy, and we hypothesize in difficult cases of TLE, knowledge of the EN
could help us to localize the EZ. Even with recent progress from studies of the EN, we still do not know the full
extent of brain abnormalities that define the EN, what part is necessary for generating seizures, or how much of
the EN needs to be removed to eliminate seizures. This project addresses these issues and we have developed a
comprehensive approach to study them, including novel structural and diffusion MRI and EEG functional
connectivity tests, as well as studies of high frequency oscillations (HFOs), which are a potential biomarker of
the EZ. We will apply this approach to presurgical patients with suspected TLE who require invasive EEG tests
as part of their standard diagnostic care. To help us define the EN in Aim 1, we will evaluate structural MRI for
gray matter abnormalities and morphological covariance between brain areas; in Aim 2, we will assess
diffusion MRI for white matter microstructural and fiber tract anomalies; in Aim 3, we will use a new approach
called gamma event coupling in combination with unit and HFO recordings to investigate the functional
connectivity encompassing the EN and identify which parts of it are generating seizures and spread; and lastly
in Aim 4, we will determine which components of the EN and how much of it needs to be removed to eliminate
seizures. In this project, defining the EN should provide important information on the structural and
functional mechanisms generating seizures, and ultimately this will help us to localize the EZ, improve
diagnosis, advance surgical and non-surgical therapies, develop new therapies, and increase the likelihood for
seizure freedom.
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会议论文
Defining the Epileptogenic Network and Identifying which Components Generate Seizures
-
批准号:10201767
-
项目类别:
-
资助金额:$54.58万
-
财政年份:2018
-
负责人:Richard Staba
-
依托单位:
Defining the Epileptogenic Network and Identifying which Components Generate Seizures
-
批准号:10401487
-
项目类别:
-
资助金额:$54.01万
-
财政年份:2018
-
负责人:Richard Staba
-
依托单位:
Mapping Cortical Anatomical and Electrophysiological Abnormalities in Human MTLE
-
批准号:8108991
-
项目类别:
-
资助金额:$33.69万
-
财政年份:2011
-
负责人:Richard Staba
-
依托单位:
Mapping Cortical Anatomical and Electrophysiological Abnormalities in Human MTLE
-
批准号:8417846
-
项目类别:
-
资助金额:$32.51万
-
财政年份:2011
-
负责人:Richard Staba
-
依托单位:
Mapping Cortical Anatomical and Electrophysiological Abnormalities in Human MTLE
-
批准号:8217082
-
项目类别:
-
资助金额:$33.69万
-
财政年份:2011
-
负责人:Richard Staba
-
依托单位:
Mapping Cortical Anatomical and Electrophysiological Abnormalities in Human MTLE
-
批准号:8606662
-
项目类别:
-
资助金额:$33.35万
-
财政年份:2011
-
负责人:Richard Staba
-
依托单位:
海外基金