Awake surgery with direct electrical stimulation mapping and real-time cognitive monitoring for functionally guided tumor resection: how we do it

Abstract

Background

Awake surgery is the reference for diffuse low-grade glioma resection, allowing maximal tumor removal while preserving neurocognitive functions. It is also applicable to other brain tumors. However, key technical elements must be followed to ensure optimal conditions for intraoperative cognitive testing and reliable functional mapping.

Method

We describe the asleep–awake–asleep technique with real-time cognitive monitoring and provide practical guidance for safe and effective implementation.

Conclusion

Success relies on rigorous intraoperative standards to optimize functional mapping. Beyond oncological outcomes, this surgical philosophy preserves quality of life by respecting individual brain organization, reflecting a shift toward personalized functional neurooncology.

Supplementary Information

The online version contains supplementary material available at 10.1007/s00701-025-06656-8.

Introduction

Awake surgery with direct electrical stimulation (DES) was first developed for epilepsy treatment in the early twentieth century [10] and later adapted for brain tumor resection [2]. It is now widely recognized as the gold standard for diffuse low-grade glioma (DLGG) and is also applicable to other intraparenchymal brain tumors. This approach relies on real-time cognitive monitoring to guide resection based on the patient’s individual connectome, rather than on anatomical tumor boundaries, which are absent in diffuse gliomas. This paradigm shift, rooted in the interplay between neuroscience and neurosurgery, has significantly improved onco-functional outcomes, yielding less than 2% permanent deficits, high cognitive preservation, and approximately 94% return-to-work rates while increasing survival beyond 20 years [9]. However, achieving such results requires adherence to key technical and practical principles with the goal to optimize intraoperative cognitive testing. This article outlines practical recommendations for the asleep–awake–asleep protocol used in our centers.

Relevant surgical functional anatomy

Supratentorial tumors may affect any brain region, involving both cortical and subcortical structures. Primary cortices (motor, somatosensory, visual), major white matter tracts, and central grey nuclei have limited capacity for functional compensation. In contrast, regions involved in more distributed networks may already be compensated at the time of surgery, making them resectable [5]. These anatomo-functional considerations are also influenced by the natural history of the disease, its anatomical extension, and the patient’s individual profile. All these aspects must be carefully anticipated preoperatively, as they define the true limits of resection and the brain’s potential for functional compensation [8]. Importantly, cognitive tasks should be tailored not only to the lesion’s topography and extent but also to the patient’s specific characteristics, including profession, lifestyle, interests, and personal goals. This patient-centered strategy, grounded in the principles of personalized medicine, ensures that functional mapping reflects each patient’s real-life needs and helps preserve quality of life [7].

Description of the technique

• A.Preoperatively.

  - A comprehensive cognitive and language assessment by a specialized speech therapist and/or neuropsychologist is essential to determine baseline performance, select relevant intraoperative tasks, and prepare the patient technically and psychologically.

  - Preoperative sedatives are avoided, including the night before surgery, and antiseizure medication is optimized to reduce intraoperative risk.

• B.Intraoperatively (Video).

  1. Positioning

  The patient lies himself in lateral decubitus, contralateral to the tumor. The upper limb is supported but free to move (Fig. 1). Proper positioning avoids pressure points that could impair cooperation.

  2. Surgical site preparation

  After induction and laryngeal mask placement (instead of using a tube to avoid damage to vocal cords) [1], the head is secured in a neutral position using a three-pin clamp, allowing access to the face for later re-intubation (Fig. 2a and 2b). In addition to properly exposing the tumor boundaries, the incision should expose the ventral premotor cortex (vPMC) for DES calibration (see further, point 4). Local anesthesia (lidocaine or ropivacaine, with epinephrine for hemostasis) must be infiltrated on the pins (Fig. 2c) and the skin trace (Fig. 2d), including the skin split, under toxicity thresholds. Linear incisions should be avoided to ensure adequate exposure allowing positive mapping. Draping must preserve access to the face and eyes, using opaque rather than transparent drapes to isolate the patient and the evaluator from the surgical field (Fig. 2e and 2f).

  3. Dura opening

  Once the bone flap removed and temporal muscle infiltration reinforced, general anesthesia may be discontinued before dural opening to prevent brain swelling at the time of extubation. For re-operations, the dura should be carefully opened prior to awakening, as adhesions may prolong this step. Tumor boundaries may be identified using intraoperative ultrasound, which is less affected by brain shift than neuronavigation.

  4. Cortical mapping

  Cortical mapping begins once the patient is awake and fully cooperative. The neuropsychologist or speech therapist conducts cognitive tasks, interpreting and reporting to the surgeon errors and subtle behavioral changes that may reflect network disruption (Fig. 3a). Importantly, evaluators are blind to the timing of stimulation to avoid bias (no bell or sound signal). Stimulation intensity is calibrated at the vPMC by inducing speech arrest without facial or laryngeal movement, starting at 1 mA and increasing by 0.5 mA increments, never exceeding 5 mA to minimize the risk of seizures. Cold sterile saline is kept ready for immediate cortical application in case a seizure occurs. Once the effective threshold is established, it remains constant throughout the procedure. Mapping must cover the exposed cortex (Fig. 3b), especially areas planned for resection or traversed to access the lesion. Functional sites are tagged with sterile labels (Fig. 3c).

  5. Tumor resection

  Coagulation should be strictly limited to the pial surface, with particular attention paid to preserving vessels that supply or drain the surrounding cortex – especially when these areas are functionally eloquent. Resection is optimally performed using a subpial dissection technique, allowing progression while protecting the vessels located within the sulci. Bleeding should be managed using local hemostatic agents rather than coagulation, which may compromise vascular territories and lead to ischemic injuries of variable extent. Such lesions can disrupt functional connectivity, result in cognitive impairment, and limit the brain’s potential for plasticity.

  For deep-seated lesions (such as in the insula or cingulate gyrus), a transcortical approach is systematically preferred over a transsulcal route to minimize vascular risk. Cortical mapping enhances the safety of this approach by identifying functional cortical areas and providing a reliable and vessel-free corridor. This strategy is also valuable in cases of highly vascularized tumors such as glioblastomas, or in the presence of altered brain parenchyma -as observed in bulky tumors or during reoperations. By enabling resection through non-altered brain tissue, connectome-based surgery not only minimizes the need for coagulation -thereby reducing ischemic risk- but also allows for functionally guided lobectomies (i.e., supratotal resection), tailored to the patient’s individual functional organization.

  6. Real-time and continuous cognitive assessment

  During intraoperative mapping (Fig. 4), constant multi-tasking under time constraints may be used to mirror (dys)synchronization within and between neural networks, while enhancing the sensitivity of behavioral monitoring by sustaining a high cognitive load throughout resection, possibly by regularly switching from a combination of tasks to another one [3]. Distractions (ultrasound dissectors, noise, unnecessary staff movement) must be avoided. Some regions (e.g., skull base, Sylvian fissure) may be painful to the touch and should be avoided during the awake phase [4]. The duration of the awake phase should ideally remain within two hours, as prolonged procedures can lead to an increased risk of errors during functional testing due to patient fatigue. To this end, a disconnection surgery turning around the tumor core is recommended, rather than a classical debulking surgery. In all cases, resection should be extended up to deep functional structures identified by subcortical stimulation.

  7. Asleep phase

  Once functional limits have been reached, anesthesia is re-induced. Intubation (with a tube) is preferred to protect the airway, especially if the closure is long (for example, when one or more lobectomies still need to be performed depending on previously identified functional limits) [1]. Closure follows standard craniotomy procedures.

• C.Postoperatively.

  - A cognitive assessment should be repeated before discharge by the same neuropsychologist or speech therapist to ensure continuity. This step informs tailored rehabilitation for the patient.

  - Early initiation of speech, cognitive, and/or physiotherapy rehabilitation is crucial to promote neuroplasticity and functional recovery within the first three months [6].

Fig. 1.

Patient comfortably positioned in lateral decubitus, before general anesthesia, with the contralateral arm left free to allow monitoring of movements

Fig. 2.

Setup of patients undergoing awake craniotomy. Positioning in right (a) or left (b) lateral decubitus, identical to the pre-anesthesia phase, with the head secured in a three-pin clamp. Local anesthesia of the pin sites (c) and planned incision line (d) after skin preparation. Draping with opaque surgical drapes, separating the operative side (e) from the patient-facing side (f), which remains open for anesthetic management and neuropsychological monitoring

Fig. 3.

Cortical mapping during awake craniotomy. (a) The patient performs cognitive tasks while executing a predefined arm movement under the supervision of a dedicated neuropsychologist. (b) Bipolar electrostimulation of the exposed cortex to identify functional areas to be preserved during tumor resection. (c) Cortical mapping with sterile labels marking functional cortical areas identified by direct electrostimulation

Fig. 4.

Subcortical mapping during tumor resection. (a) Bipolar electrostimulation of white matter while the patient continuously performs cognitive and movement tasks, to identify functional boundaries of resection. (b) Subcortical mapping with sterile labels marking functional white matter pathways identified by direct electrostimulation

Indications

Awake surgery is the reference technique for DLGG resection, and is also appropriate for selected high-grade gliomas, circumscribed gliomas, metastases, and cavernous malformations. It should be noted that this surgical strategy can be fully integrated into the operative schedule of a hospital neurosurgical center.

Limitations

Any condition that prevents reliable intraoperative testing, such as significant preoperative neurological or cognitive deficits, extreme age (though no absolute limit), or respiratory/metabolic comorbidities (e.g., COPD, obesity) that may affect ventilation or increase aspiration risk [1].

How to avoid complications

Patient selection and preparation is crucial and requires a multidisciplinary assessment by surgical, anesthesiology, and neuropsychology teams. Tools such as neuronavigation, intraoperative MRI, or tumor fluorescence only provide anatomical guidance (with their own limitations) and do not account for individual functional limitations and should therefore be forbidden. In this context, the intervention of a dedicated neuropsychologist or speech therapist, although time-consuming in assessment, proves to be cost-effective, largely offsetting the use of the previously mentioned very expensive technologies, while ensuring reliable functional mapping. Moreover, due to its low cost and universal availability, this human resource is applicable worldwide.

Specific information for the patient

Patients must be fully informed about the surgical procedure, including their active intraoperative role. Postoperative rehabilitation is essential to ensure functional recovery and quality of life preservation.

Clinical vignette

A 38-year-old right-handed woman, working as an obstetric midwife, presented with a first generalized seizure. She had no prior medical history and exhibited no neurological or cognitive symptoms before this event. Brain MRI revealed a right-sided tumor located in the supplementary motor area (SMA), suggestive of a DLGG, with no radiological features of anaplasia (Fig. 5a).

Fig. 5.

MRI of the illustrative case. (a) Preoperative FLAIR MRI in axial, coronal and sagittal planes, showing a probable DLGG involving the right supplementary motor area (SMA) and the underlying white matter. (b) Postoperative MRI at 3 months in the same planes, showing the resection cavity and a small tumor residue (< 2cm³) in its posterior part, within the premotor networks

At three-month follow-up, while seizures were well controlled with antiepileptic medication, MRI showed a slight increase in tumor volume (+ 1 mm in mean diameter), estimated at approximately 16 cm³, further supporting the diagnosis of DLGG. Neuropsychological and language assessments were within normal limits.

Given the tumor’s location within the dorsal premotor region, the patient was thoroughly informed about the potential risk of persistent deficits in motor abilities and verbal fluency due to involvement of the SMA cortex and the underlying white matter tracts—namely the frontal aslant tract and fronto-striatal tract. Additionally, the patient was counseled about the risk of disruption to multimodal semantic processing due to the proximity of the white matter lateral to the tumor, beneath the middle frontal gyrus, where fibers of the inferior fronto-occipital fasciculus are located.

The patient expressed a strong preference to avoid any permanent speech or motor deficits, particularly as intact bimanual coordination was essential for her professional activities and hobbies. Awake surgery was therefore proposed and performed according to the protocol described previously.

During the awake phase, DES at the posterior tumor border elicited transient disruption of motor and speech initiation, as expected. Semantic processing disruption -both verbal and non-verbal- were also transiently elicited when stimulating the deep lateral white matter. In accordance with the preoperative strategy discussed with the patient, resection was intentionally limited, sparing a small portion of the tumor in its posterior part.

In the immediate postoperative period, the patient presented with a mild supplementary motor area (SMA) syndrome, characterized by transient hypokinesia and reduced verbal fluency. She underwent targeted cognitive rehabilitation, with a focus on speech fluency and executive functions. All symptoms resolved within three months. Follow-up neuropsychological and language assessments showed scores comparable to preoperative baseline. Histopathological analysis confirmed a WHO grade 2 IDH-mutant astrocytoma. The three-month postoperative MRI demonstrated a small residual tumor in the posterior wall of the cavity, as expected (Fig. 5b). The patient was able to return to work as before, initially part-time and subsequently full-time. Given the small residual volume (< 2 cm³) and its typical DLGG behavior, no adjuvant treatment was initiated, and a six-month clinical and radiological follow-up was planned.

Conclusion

Awake surgery with real-time cognitive monitoring, guided by the patient’s individual connectome, offers a reliable and effective strategy for maximal safe tumor resection. Its success relies on a dedicated multidisciplinary team as well as strict adherence to key procedural steps to optimize intraoperative functional mapping. Beyond improved oncological outcomes, this strategy/new philosophy is demonstrated to preserve quality of life by respecting the brain’s unique functional architecture. It should therefore be considered not just as a surgical technique, but as a paradigm shift toward personalized neurosurgical oncology.

Key points summary

• Awake surgery with direct electrostimulation mapping is the gold standard for low-grade glioma resection, and can be applied to other selected intraparenchymal brain tumors

• This new surgical strategy philosophy relies on real-time cognitive monitoring to guide resection based on the patient’s individual connectome rather than anatomical tumor margins

• Multidisciplinary team -including neurosurgeons, anesthesiologists, and neuropsychologists or speech therapists- is essential for patient selection and preparation, intraoperative mapping, and optimal technical conditions (positioning, draping, communication)

• The bone flap should be large enough to uncover the brain tumor, its margin, and the ventral premotor cortex for DES calibration (positive cortical mapping)

• Coagulation must be strictly limited to the pial surface, while subpial dissection allows preservation of cerebral vessels and thus limits the risk of vascular injury within the connectivity

• For deep-seated lesions, cortical mapping enhances transcortical routes through non-functional and vessel-free corridor compared to transsulcal approaches

• Disconnection surgery revolving around the tumor core is recommended, rather than classic debulking surgery, allowing safer, faster and wider tumor resection

• Constant multi-tasking under time constraints by regularly switching between task combinations may be used to enhance the sensitivity of behavioral monitoring by sustaining a high cognitive load throughout resection

• In all cases, the resection should be extended to the deep functional structures identified by subcortical stimulation

• Early initiation of speech, cognitive, and/or physiotherapy rehabilitation is crucial to promote neuroplasticity and functional recovery within the first three months

Supplementary Information

Below is the link to the electronic supplementary material.

Author Contribution

F.A. and H.D. wrote the main manuscript text F.A. prepared the figures and the video F.A. and H.D. approved the final version of the article.

Funding

No funding.

Data Availability

No datasets were generated or analysed during the current study.

Declarations

Competing interest

The authors declare that they have no conflict of interest.

Ethical Approval

This article does not report a clinical study and did not require formal ethics committee approval. All patients whose images or videos are included provided informed consent for their use in this publication.