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%的癫痫患者对药物治疗无效，癫痫手术是一种有效的治疗方法。 替代.我们需要更好的方法来识别癫痫皮层，必须将其切除， 无癫痫发作。通常需要进行慢性颅内EEG（iEEG）遥测记录，这会带来风险， 不适、不便和成本。拟议的项目旨在开发一种新的方法，以更安全地规划 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 脑电振荡（HFO）是致癫痫脑的候选生物标志物，包括短暂（25-200毫秒）的EEG 频谱内容在80-600 Hz之间的事件。HFO率在癫痫发作区升高 (SOZ)，但HFO率也可能在致痫区（EZ）升高，这是一个假设的概念， 必须切除以获得术后癫痫发作自由的区域。SOZ并不总是表示 在EZ的位置。HFO速率用于确定SOZ位置的准确性尚未确定， 切除区域的HFO率与切除区域外的HFO率是否具有不同的预后价值 区域，也需要澄清。我假设在急性发作期间测量的发作间期HFO率， 手术记录具有足够的准确性，可用于定位EZ，以证明减少或消除住院iEEG的合理性 遥测用于颞叶癫痫（TLE）患者，但不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检验这一假设，该研究旨在评估医学上患有 难治性局灶性癫痫。本研究的目标1将确定并比较HFO率的准确性， 识别睡眠期间慢性记录和深度时急性记录中的SOZ和EZ 局灶性癫痫患者的电极植入。这将通过以下方式实现：1）评估 HFO生物标志物预测与临床结局之间的一致性，以区分SOZ的分类器 从EZ使用受试者工作特征（ROC）方法，和2）评估率的准确性 HFO生物标志物在特定神经解剖结构和位置中的出现。目标2将 确定切除和残留HFO生物标志物率的预测值， 术中皮质电图（ECoG）检查切除术后癫痫发作。临床终点 目的是剩余HFO率对癫痫复发的预测值将超过 无癫痫发作的切除HFO率。这项研究性学习与我的职业发展紧密结合 该计划侧重于生物统计学，临床试验设计和神经工程的课程工作。四位导师 是公认的临床和转化癫痫研究的领导者，在癫痫研究方面具有特定的专业知识， HFO和专门的统计学家将提供教学和技术专业知识，以确保研究 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.