Intraoperative Neurophysiological Monitoring in Brain Tumor Surgery: Prospective Cohort Studies

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:

1. CCEP monitoring lacks standardization and clinical validation, and its use varies considerably across clinical practice. 2. Intraoperative CCEP signal changes are associated with postoperative language impairment and can be used to establish clinically relevant warning thresholds. 3. IOM with MEP improves motor function preservation and/or increases the extent of safe tumor resection compared with surgery without IOM. 4. 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."