Reducing or obviating the need for chronic intracranial electroencephalogram telemetry for epilepsy surgery patients by utilizing inter-ictal HFO rates: A study of diagnostic accuracy

摘要 30%-40%的癫痫患者对药物发作无反应，癫痫手术是有效的治疗方法 另类选择。我们需要更好的方法来识别必须切除的致痫皮质以呈现患者 没有癫痫发作。通常需要进行慢性颅内脑电(IEEG)遥测记录，这带来了风险， 不适、不便和昂贵。拟议的项目旨在开发一种新的方法来更安全地计划 通过减少或消除对慢性颅内监测的需要来进行癫痫手术。高频 振荡(HFO)是致痫脑的候选生物标志物，由短时(25-200毫秒)脑电组成 光谱含量在80-600赫兹之间的事件。癫痫发作区HFO发生率较高 (SOZ)，但HFO发生率也可能在致痫区(EZ)升高，这一假设构成了一个概念 为获得术后癫痫发作自由而必须切除的区域。Soz并不总是指示 EZ的位置。未确定确定SOZ位置的HFO比率的准确性，以及 切除区域的HFO发生率与切除外的HFO发生率是否具有不同的预后价值 地区，也需要澄清。我假设在发作间期测得的HFO率在急性期内- 手术记录有足够的准确性来定位EZ，以证明减少或消除住院患者iEEG的合理性 遥测用于颞叶癫痫(TLE)患者，但不适用于颞外局灶性癫痫患者。 我们将在一项观察性临床研究中验证这一假设，该研究对内科疾病患者的诊断准确性进行了研究。 难治性局灶性癫痫。研究的目标1将确定和比较HFO比率的准确性 确定睡眠期间慢性记录和深度时急性记录中的SOZ和EZ 电极植入在局灶性癫痫患者中的应用这将通过1)评估 HFO生物标志物预测与临床结果之间的一致性以区分SOZ的分类 使用接收器操作特征(ROC)方法从EZ，以及2)评估费率的准确性 在特定的神经解剖结构和位置出现HFO生物标志物的可能性。目标2将 确定切除和残留的HFO生物标志物比率的预测价值 术中进行皮层脑电检查以解除术后癫痫发作。它的临床终点是 目的是残留HFO比率对癫痫复发的预测价值将超过 切除高脂血症率以获得癫痫自由。这次研究性学习与我的职业发展紧密结合在一起 计划的重点是生物统计学、临床试验设计和神经工程方面的课程工作。四位导师 是临床和转化性癫痫研究的公认领导者，在以下方面具有特定的专业知识 HFOS和一名专门的统计员将提供教学和技术专长，以确保这项研究 进行得很好，并且我达到了我的职业发展计划的目标。

ABSTRACT Seizures fail to respond to medication in 30-40% of patients with epilepsy, and epilepsy surgery is an effective alternative. We need better methods to identify epileptogenic cortex that must be removed to render patients seizure free. Chronic intracranial EEG (iEEG) telemetry recording is often required, and this poses risk, discomfort, inconvenience, and cost. The proposed project aims to develop a new method to more safely plan epilepsy surgery by reducing or eliminating the need for chronic intracranial monitoring. High-frequency oscillations (HFOs) are a candidate biomarker of epileptogenic brain and consist of brief (25-200 msec) EEG events with a spectral content ranging between 80-600 Hz. HFO rates are elevated in the seizure onset zone (SOZ), but HFO rates may also be elevated in the epileptogenic zone (EZ) a hypothetical concept constituting the area that must be excised to attain postoperative seizure freedom. The SOZ does not always indicate the location of the EZ. The accuracy of HFO rates for determining the location of the SOZ is not established, and whether HFO rates in resected regions have different prognostic value than HFO rates outside resected regions, also requires elucidation. I hypothesize that inter-ictal HFO rates measured during acute intra- operative recording has sufficient accuracy for localizing the EZ to justify reducing or eliminating inpatient iEEG telemetry for patients with temporal lobe epilepsy (TLE), but not for patients with extra-temporal focal epilepsy. We will test this hypothesis in an observational clinical study of diagnostic accuracy in patients with medically refractory focal epilepsy. Aim 1 of the study will determine and compare the accuracy of HFO rates to identify the SOZ and the EZ in chronic recordings during sleep and acute recordings at the time of depth electrode implantation in patients with focal epilepsy. This will be accomplished by 1) Assessing the concordance between HFO biomarker predictions and clinical outcomes to distinguish classifiers of SOZ from EZ using a receiver operating characteristic (ROC) approach, and 2) Assessing the accuracy of the rates of occurrence of the HFO biomarkers in specific neuroanatomical structures and locations. Aim 2 will determine the predictive value of resected and residual HFO biomarker rates recorded with electrocorticography (ECoG) during surgery for post-resection seizure freedom. The clinical endpoint of this aim is that the predictive value of residual HFO rates for seizure recurrence will exceed the predictive value of resected HFO rates for seizure freedom. This research study is closely integrated with my career development plan that focuses on course work in biostatistics, clinical trial design, and neuroengineering. Four mentors who are recognized leaders in clinical and translational epilepsy research, with a specific expertise in the study of HFOs, and a dedicated statistician will provide the teaching and technical expertise to assure that the study is conducted properly and that I meet the aims of my career development plan.