13.1 Introduction

The goal of brain lesion surgery is to maximize the extent of resection while preserving the quality of life. This is particularly true in neuro-oncology, since a greater extent of tumor removal is associated with a significant increase in overall survival for low-grade gliomas, ^{1 ,​ 2} high-grade gliomas, ^{3 ,​ 4} and/or metastases. ⁵ It has been proposed to achieve supratotal resection, that is, to take a margin around the signal abnormality visible on magnetic resonance imaging (MRI), both in diffuse low-grade glioma ⁶ and glioblastoma, ⁷ in order to improve the oncological outcomes.

To optimize the oncofunctional balance, the principle is to switch from a traditional image-guided resection to a mapping-based resection performed up to the individual functional boundaries, both at cortical and subcortical levels. When the lesion is located near or within eloquent structures, such as structures critical for language, awake surgery is mandatory to identify and preserve not only the cortical hubs but also the white matter tracts underpinning neural networks. Intraoperative direct electrical stimulation (DES) mapping combined with real-time cognitive monitoring throughout the resection is the sole method for allowing the detection of the subcortical pathways essential for brain functions. ⁸

Here, the purpose is to detail how cortical and axonal DES participated in improving our knowledge regarding the subnetworks mediating language as well as their dynamic interactions: such a better understanding of language connectome resulted in an improvement of the benefit-to-risk ratio of surgery for lesions involving this complex circuitry, on the condition to adapt the surgical technique accordingly.

13.2 Illustrative Case

This case is about a 25-year-old right-handed man who experienced seizures. The neurological examination was normal, but the neurocognitive assessment revealed slight disorders of verbal working memory. The MRI demonstrated an imaging typical for a diffuse low-grade glioma (despite a small enhancement in the middle of the tumor) invading the posterior part of the left inferior frontal gyrus and the lateral part of the Rolandic operculum (Fig. 13‑1). Awake surgery was performed with intraoperative DES mapping. Cortically, the ventral premotor cortex (inducing speech arrest when stimulated) and the primary cortex of the face (eliciting involuntary face movement with dysarthria during stimulation) were identified and preserved as the posterior limit of the resection. Of note, the so-called Broca area did not generate any disturbances when stimulated. Glioma removal was achieved according to functional boundaries, as well as at the subcortical level. Indeed, axonal DES at the end of resection allowed the detection of the anterior part of the dorsal route (causing articulatory troubles) as well as the frontal part of the ventral route (inducing semantic paraphasias). A complete resection was achieved, as shown by the postoperative MRI, and the patient improved his neuropsychological scores after surgery in comparison with the preoperative scores, especially concerning verbal working memory, thanks to postsurgical cognitive rehabilitation.

13.3 Evidence-based Clinical Decisions

A recent review of the literature confirmed that maximal safe resection is the first therapeutic option in glioma patients, ⁹ as already recommended by the current guidelines. ¹⁰

Beyond the oncological considerations, preoperative functional neuroimaging is not reliable enough at the individual level for language mapping. While allowing a noninvasive mapping of the entire brain, functional MRI (fMRI) and diffusion tensor imaging cannot be used in clinical practice for surgical selection and planning, because they do not provide a direct reflection of the real neural functions but only a very indirect approximation of brain processing based upon biomathematic reconstructions. At the cortical level, correlation between preoperative language fMRI and intraoperative DES revealed that fMRI sensitivity and specificity were only 37.1 and 83.4%, respectively. ¹¹ An open international tractography challenge including 20 research groups demonstrated that algorithms produce tractograms which contain many more invalid than valid bundles, and that half of these invalid bundles occur systematically across research groups. ¹²

By contrast, a meta-analysis of the literature examining over 8,000 patients who underwent excision for low-grade or high-grade gliomas evidenced that the use of intraoperative DES led to a significant decrease of postoperative permanent worsening, while the rate of surgical selection for tumors involving eloquent structures, especially language, increased. The extent of resection was also improved. ¹³ This is in agreement with a large series using awake mapping that reported less than 2% risk of severe persistent deficit. ^{14 ,​ 15}

In summary, the current literature supports early and radical resection under the guidance of intraoperative DES mapping for brain tumors.