Use of a Tonometer to Identify Focal Cortical Dysplasia and Tuberous Sclerosis Complex During Pediatric Epilepsy Surgery
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 试验地点
- 4
- 主要终点
- Brain tissue stiffness measurements in mmHg as assessed by intraoperative use of a digital tonometer on presumed normal cerebral cortex
研究概览
简要总结
Refractory epilepsy, meaning epilepsy that no longer responds to medication, is a common neurosurgical indication in children. In such cases, surgery is the treatment of choice. Complete resection of affected brain tissue is associated with highest probability of seizure freedom. However, epileptogenic brain tissue is visually identical to normal brain tissue, complicating complete resection. Modern investigative methods are of limited use.
An important subjective assessment during surgery is that affected brain tissue feels stiffer, however there is presently no way to determine this without committing to resecting the affected area. It is hypothesized that intra-operative use of a tonometer (Diaton) will identify abnormal brain tissue stiffness in affected brain relative to normal brain. This will help identify stiffer brain regions without having to resect them.
The objective is to determine if intra-operative use of a tonometer to measure brain tissue stiffness will offer additional precision in identifying epileptogenic lesions.
In participants with refractory epilepsy, various locations on the cerebral cortex will be identified using standard pre-operative investigations like magnetic resonance imagin (MRI) and positron emission tomography (PET). These are areas of presumed normal and abnormal brain where the tonometer will be used during surgery to measure brain tissue stiffness. Brain tissue stiffness measurements will then be compared with results of routine pre-operative and intra-operative tests. Such comparisons will help determine if and to what extent intra-operative brain tissue stiffness measurements correlate with other tests and help identify epileptogenic brain tissue.
24 participants have already undergone intra-operative brain tonometry. Results in these participants are encouraging: abnormally high brain tissue stiffness measurements have consistently been identified and significantly associated with abnormal brain tissue.
If the tonometer adequately identifies epileptogenic brain tissue through brain tissue stiffness measurements, it is possible that resection of identified tissue could lead to better post-operative outcomes, lowering seizure recurrences and neurological deficits.
详细描述
Rationale: Refractory epilepsy, meaning epilepsy that no longer responds to medication, is a common neurosurgical indication in children. Focal cortical dysplasia (FCD) is the most common cause. Tuberous sclerosis complex (TSC) is a rare genetic disease causing epilepsy in over 90% of affected patients. This epilepsy can also become refractory to medication. In such cases of FCD or TSC, surgery is the treatment of choice. Complete resection of brain tissue affected by FCD or TSC is associated with highest probability of seizure freedom. However, epileptogenic brain tissue is visually identical to normal brain tissue, complicating complete resection. Modern investigative methods such as magnetic resonance imaging (MRI), electro-encephalography (EEG) and positron emission tomography (PET), are of limited use. Failure to achieve complete resection may lead to seizure recurrence, which is costly and requires additional surgeries, increasing risks of morbidity and mortality compared to achieving remission.
Changes in tissue stiffness due to an underlying pathology are common in medicine, especially in neurological disorders. An important subjective assessment during epilepsy surgery, particularly in FCD cases, is that affected brain tissue feels stiffer. However, there is currently no way to determine stiffness without committing to resecting the affected area.
Hypothesis: Epileptogenic brain tissue stiffness, as measured intra-operatively using a digital tonometer (Diaton), will likely be increased relative to normal brain tissue. This could allow identification of regions of higher stiffness without having to commit to resection.
The tonometer is a widely-used and FDA-approved tool to measure intraocular pressure. It is a simple and reliable tool to measure brain tissue stiffness without obstructing the operative field. It requires only minimal contact in brain tissue.
This study is multicentric and includes University of California, Los Angeles (UCLA) Mattel Children's Hospital in Los Angeles and Sainte-Justine University Hospital in Montreal. Results from 24 participants in a preliminary study from UCLA Mattel Children's Hospital were encouraging, prompting expansion of the study to include both sites.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
盲法说明
No masking. Participants as well as caregivers and investigators will all be aware that patients are undergoing intra-operative brain tonometry (single arm study).
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants with epilepsy who candidates for surgical treatment as established by a multidisciplinary committee specialized in epilepsy.
- •Participants undergoing resective surgery for epilepsy of dysplastic (examples: focal cortical dysplasia, tuberous sclerosis, hemimegalencephaly, polymicrogyria) or non-dysplastic etiology (examples: developmental tumors, gliosis, stroke, Rasmussen encephalitis, Sturge-Weber syndrome).
排除标准
- •Lesion of interest located in a difficult to access region, such as paralimbic structures, insula, depth-of-sulci or inter-hemispheric.
结局指标
主要结局
Brain tissue stiffness measurements in mmHg as assessed by intraoperative use of a digital tonometer on presumed normal cerebral cortex
时间窗: Intraoperative
Brain tonometry is a novel diagnostic approach, therefore normal and abnormal brain tissue stiffness values are not known. Measurements will be taken on presumed normal cerebral cortex, based on results of preoperative evaluations (magnetic resonance imaging, electro-encephalography, positron emission tomography), to establish potential normal brain tissue stiffness values.
Brain tissue stiffness measurements in mmHg as assessed by intraoperative use of a digital tonometer on presumed pathological cerebral cortex
时间窗: Intraoperative
Brain tonometry is a novel diagnostic approach, therefore normal and abnormal brain tissue stiffness values are not known. Measurements will be taken on presumed pathological (ex.: focal cortical dysplasia, tuberous sclerosis complex) cerebral cortex, based on results of preoperative evaluations (magnetic resonance imaging, electro-encephalography, positron emission tomography), to establish potential pathological brain tissue stiffness values.
Correlation between brain tissue stiffness measurements in mmHg as assessed by novel intraoperative use of a digital tonometer and results of standard perioperative evaluations, using a 3D model of each brain
时间窗: Perioperative
Precise stereotactic coordinates for each brain tissue stiffness measurement will be recorded in a neuronavigation software. This will allow aggregation of brain tissue stiffness measurements and results of routine preoperative (MRI, EEG, PET), as well as intra-operative tests (ECoG, histopathological analysis of resected brain tissue) on a 3D model of each patient's brain. With this method, each brain tissue stiffness measurement can be compared to presence or absence of an underlying lesion on MRI; to presence or absence of epileptogenic foci on EEG; to presence of iso- or hypometabolism on PET; to presence or absence of epileptogenic foci on ECoG; to pathological diagnosis and severity of cortical disorganization on histopathological analysis. This will give insight into how well brain tissue stiffness measurements correlate with, and potentially identify, structural and functional epileptic brain anomalies.
次要结局
- Seizure freedom as assessed clinically on standard postoperative follow-up through study completion, up to 36 months(Through study completion, up to 36 months)
- Surgical complications as assessed clinically on standard postoperative follow-up through study completion, up to 36 months(Through study completion, up to 36 months)
研究者
Aria Fallah
Aria Fallah, MD, MSc, FRCSC, FAANS, FAAP; Neurosurgery
University of California, Los Angeles