Intraoperative Monitoring of Motor, Visual and Cortico-cortical Evoked Potentials in Brain Tumor Surgery Under General Anesthesia: Prospective Cohort Studies
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 166
- 试验地点
- 1
- 主要终点
- CCEP signal changes
研究概览
简要总结
BACKGROUND Brain tumor surgery requires balancing two competing priorities: maximizing the extent of tumor resection to improve survival while preserving neurological function. This is particularly challenging in eloquent brain tumor surgery, where even minor injury may result in permanent loss of functions such as muscle paralysis, language impairment, or visual loss, substantially affecting patients' independence and quality of life.
Intraoperative neurophysiological monitoring (IOM) combines functional mapping to identify eloquent structures with continuous monitoring of the integrity of eloquent structures during tumor resection. IOM with motor evoked potentials (MEP) is widely used to map and monitor motor-eloquent structurse but still lack high-quality evidence demonstrating patient-related benefit. Other modalities, including cortico-cortical evoked potentials (CCEP) for language monitoring and visual evoked potentials (VEP) for visual pathway monitoring, are promising but lack standardization and further clinical validation.
AIM To strenghten the evidence base and clinical application of IOM in eloquent brain tumor surgery, enabling safer and more effective surgical treatment.
HYPOTHESES
The project is based on the following hypotheses:
- CCEP monitoring lacks standardization and clinical validation, and its use varies considerably across clinical practice.
- Intraoperative CCEP signal changes are associated with postoperative language impairment and can be used to establish clinically relevant warning thresholds.
- IOM with MEP improves motor function preservation and/or increases the extent of safe tumor resection compared with surgery without IOM.
- Intraoperative VEP signal changes are associated with postoperative visual impairment and can be used to establish clinically relevant warning thresholds.
PROJECT DESIGN The project comprises four unprecedented studies. Part 1 is a scoping review on CCEP monitoring to evaluate current clinical practice and evidence gaps.
Part 2 is a prospective observational cohort study including adult patients undergoing resection of language-eloquent brain tumors in either general anesthesia or asleep-awake-asleep setting which evaluates the association between intraoperative CCEP signal changes and postoperative language impairment, and explores clinically relevant warning thresholds.
Part 3 is a randomized controlled trial in adult patients undergoing resection of motor-eloquent brain tumors which compares surgery performed using IOM with MEP versus no IOM to evaluate its effect on postoperative motor function and extent of tumor resection.
Part 4 is a prospective observational cohort study including adult patients undergoing visual-eloquent transsphenoidal or transcranial surgery for tumors involving the visual pathways. It evaluates the association between intraoperative VEP signal changes and postoperative visual impairment, and explores clinically relevant warning thresholds.
Standardized clinical assessments, advanced neuroimaging, and appropriate statistical analyses will be used for this purpose.
LIMITATIONS Variability between patients, tumor characteristics, and surgical procedures may complicate interpretation of intraoperative signals. In particular, VEP recordings may be affected by physiological and technical variability. Furthermore, ethical and safety considerations mean that not all patients will be eligible for every part of the project.
EXPECTED OUTCOME AND IMPACT Brain tumors are associated with substantial morbidity, permanent loss of function, and mortality. Even modest improvements in functional preservation and the extent of safe tumor resection may significantly improve survival, independence, quality of life, and return to daily activities.
The project is expected to generate unprecedented clinical evidence on IOM in eloquent brain tumor surgery through the first randomized controlled trial evaluating the patient-related benefits of IOM with MEP, and the first prospective studies on CCEP monitoring in awake and general anesthesia setting and VEP monitoring of the entire visual pathway. By addressing major evidence gaps, the project will strengthen the evidence base for IOM, improve interpretation of IOM signals and surgical decision-making, and support rapid implementation into clinical practice locally as well as impacting the use of IOM world wide.
Ultimately, the project is expected to enable safer and more effective brain tumor surgery with a lower risk of permanent motor, language, and visual impairment, improved survival and quality of life, and reduced need for rehabilitation and supportive care, thereby improving patient safety and enabling more precise and effective surgical treatment.
Furthermore, the project is related to the 3rd United Nations sustainable development goal: "Ensure healthy lives and promote well-being for all at all ages."
详细描述
BACKGROUND Brain tumor surgery requires balancing two competing priorities: maximizing the extent of tumor resection (EOR) while preserving neurological function to reach maximal safe resection. This balance is particularly challenging in eloquent brain areas, where even minor injuries may result in permanent loss of function such as muscle paralysis, language impairment, or visual loss.
Intraoperative neurophysiological monitoring (IOM) combines functional mapping to identify eloquent structures with continuous monitoring of their integrity during tumor resection. IOM with motor evoked potentials (MEP) is widely used during surgery in general anesthesia or asleep-awake-asleep setting to localize and monitor the precentral gyrus (motor cortex) and corticospinal tract (CST). Continuous stimulation of the precentral gyrus monitors CST integrity throughout resection, while subcortical motor mapping within the resection cavity estimates the distance to the CST and guides the extent of safe resection. Significant warning criteria include a >50% reduction in MEP amplitude or a 20% increase in stimulation threshold, while lower subcortical stimulation thresholds indicate increasing proximity to the CST (approximately 1 mA=1 mm). A subcortical resection limit of 3 mA is usual although lower thresholds can be safe. Combined with diffusion tensor imaging (DTI), MEP monitoring has retrospectively been associated with greater extent of resection and improved long-term survival. Although widely adopted, high-quality evidence demonstrating patient-related benefit remains lacking.
IOM with CCEP is promising for language-eloquent brain tumor surgery and has been studied in general anesthesia and asleep-awake-asleep settings. Direct cortical stimulation of one language area (Broca's or Wernicke's area) with recording from the other enables monitoring of subcortical language tract function, including the arcuate fasciculus (AF) and superior longitudinal fasciculus (SLF). During surgery in asleep-awake-asleep setting, CCEP monitoring complements cortical and subcortical language mapping which temporarily disrupts the patients' speech ability, looking for speech arrest and phonological paraphasia which is linked to AF function disruption. CCEP waveforms comprise positive (P1, P2) and negative (N1, N2) deflections. A previous study by Seidel et al. (co-applicant) demonstrated an association between N2 latency changes during awake surgery and postoperative language impairment. However, it remains unclear whether amplitudes, latencies, or both provide the most clinically relevant information, and validated warning thresholds have yet to be established. Consequently, IOM with CCEP lacks standardization and further clinical validation.
IOM with VEP can be used to monitor visual pathway function during visual-eloquent surgery. The visual pathways are normally divided into the anterior (structures from the retina to the lateral geniculate body) and posterior visual pathways (from the lateral geniculate body to the primary visual cortex). Flash stimulation delivered through light-emitting diode eye pads evoke cortical responses recorded using scalp electroencephalography (EEG), and when applicable, strip electrodes placed over the visual cortex to improve signal quality. Simultaneous electroretinography confirms adequate retinal light stimulation. Previous studies have demonstrated promising results for preserving anterior visual pathway function during prechiasmal and sellar/suprasellar tumor surgery, including endoscopic transsphenoidal surgery. However, evidence for monitoring posterior visual pathway function remains limited. Furthermore, considerable intra- and interindividual variability and signal instability reduces signal reliability and limits clinical applicability to patients with sufficient baseline visual function. VEP waveforms comprise an initial deflection called N1 and a prominent deflection called P100 (also known as P2). Focus has been on the voltage difference between N1 and P2 (P100) on one hand, and P100 amplitude on the other hand. Although a 50% reduction in the N1-P2 peak-to-peak amplitude has been proposed as a warning criterion, clinically relevant VEP signal changes and validated warning thresholds remain uncertain. Consequently, IOM with VEP lacks standardization and further clinical validation and is therefore not widely adopted.
PURPOSE
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part 1 is a litterature review.
- •Part 2 - Inclusion Criteria:
- •Patient age ≥ 18 years and ability to provide informed consent;
- •Planned resection of ≥ 1 contrast-enhancing brain tumors (tentative diagnosis high-grade glioma or metastasis) on magnetic resonance imaging (MRI) in either general anesthesia or asleep-awake-asleep setting;
- •Intended gross total or complete tumor resection;
- •Tumor located < 10 mm from the language areas (Broca's or Wernicke's) or subcortical language tracts (AF or SLF);
- •Tumor located in a language-dominant hemisphere;
- •Written informed consent.
排除标准
- •Tumors directly involving Broca's or Wernicke's area;
- •Emergency surgery;
- •Tumors involving both hemispheres.
- •Part 3 - Inclusion Criteria:
- •Patient age ≥ 18 years and ability to provide informed consent;
- •Planned resection of ≥ 1 contrast enhancing brain tumors (tentative diagnosis high-grade glioma or metastasis) on MRI in general anesthesia setting;
- •Intended gross total or complete tumor resection;
- •Tumor located < 20 mm from the precentral gyrus or CST;
- •Written informed consent.
- •Part 3 - Exclusion Criteria:
- •Tumors directly involving the precentral gyrus or CST;
- •Emergency surgery;
- •Recurrent brain tumor surgery;
- •Tumors involving both hemispheres.
- •Part 4 - Inclusion Criteria:
- •Patient age ≥ 18 years and ability to provide informed consent;
- •Planned resection of ≥ 1 contrast enhancing pituitary tumors (tentative diagnosis adenoma), contrast enhancing brain tumors (tentative diagnosis high-grade glioma, metastasis or meningioma), or non-enhancing brain tumors (tentative diagnosis low-grade glioma) on MRI in general anesthesia setting;
- •Intended gross total or complete tumor resection;
- •Tumor located < 10 mm from, or involving, the anterior or posterior visual pathways;
- •Written informed consent.
- •Part 4 - Exclusion Criteria:
- •Emergency surgery;
- •Severe visual impairment precluding reliable VEP monitoring (typically best-corrected visual acuity ≤ 0.2-0.4 on the Snellen scale).
结局指标
主要结局
CCEP signal changes
时间窗: Intraoperative
Changes in CCEP amplitudes of P1, N1, P2, N2 (μV and %) and peak latencies (ms and %), and stimulation threshold (mA and %) relative to baseline (BtW-asleep and BtW-awake)
Postoperative language function
时间窗: At 1 month, and again at 3 months in patients with speech impairment at 1 month
Postoperative language function assessed using the DuLIP language test battery and Western Aphasia Battery at approximately 1 month, and again at 3 months in patients with speech impairment at at the 1-month follow-up. Significant speech impairment is defined as a deterioration of ≥ 2 points on the DuLIP language test battery and/or ≥ 5 points or a change in aphasia severity category on Western Aphasia Battery)
Postoperative motor function
时间窗: Postoperative Day 1, and at 1-month follow-up
Postoperative motor function using the Medical Research Council scale during admission and at 1-month follow-up (0-5; 0-worse outcome, 5-better outcome).
VEP signal changes
时间窗: Intraoperative
Changes in VEP amplitudes of N1, P2 (P100), and N1-P2 peak-to-peak (μV and %) and latencies (ms and %) relative to baseline
Postoperative visual function
时间窗: At 1-2 weeks and 3 months
Postoperative visual function assessed using best-corrected visual acuity and perimetry. Significant postoperative visual impairment is defined as ≥2-line deterioration on the Snellen scale (total of 11 lines) and/or new or clinically relevant worsening of the visual field (mean deviation or pattern).
次要结局
- EOR(Postoperative Day 1)
- Karnofsky Performance Scale(At 1-month follow-up)
- National Institutes of Health Stroke Scale motor subscore(During admission (Postoperative Day 1), and at 1-month follow-up)
- Hand dynamometry(Postoperative Day 1, and at 1-month follow-up)
- 10-Meter Walk Test(Postoperative Day 1, and at 1-month follow-up)
- Six-Spot-Step Test(Postoperative Day 1, and at 1-month follow-up)
- 9-Hole Peg Test(Postoperative Day 1, and at 1-month follow-up)
- Seizure outcome(At 1-month follow-up)
- Patient Global Impression of Change(At 1-month follow-up)
- Completeness of fluorescein-guided tumor resection(Intraoperative)
- Surgeon-rated usefulness(Intraoperative)
- Tumor progression(At 3- and 6-months follow-up)