Setup Presentation and Clinical Outcome Analysis of Treating Highly Language-Eloquent Gliomas Via Preoperative Navigated Transcranial Magnetic Stimulation and Tractography

Nico Sollmann, MD, PhD; Anna Kelm; Sebastian Ille, MD; Axel Schröder; Claus Zimmer, MD; Florian Ringel, MD; Bernhard Meyer, MD; Sandro M. Krieg, MD, MBA


Neurosurg Focus. 2018;44(6):e2 

In This Article

Abstract and Introduction


Objective: Awake surgery combined with intraoperative direct electrical stimulation (DES) and intraoperative neuromonitoring (IONM) is considered the gold standard for the resection of highly language-eloquent brain tumors. Different modalities, such as functional magnetic resonance imaging (fMRI) or magnetoencephalography (MEG), are commonly added as adjuncts for preoperative language mapping but have been shown to have relevant limitations. Thus, this study presents a novel multimodal setup consisting of preoperative navigated transcranial magnetic stimulation (nTMS) and nTMS-based diffusion tensor imaging fiber tracking (DTI FT) as an adjunct to awake surgery.

Methods: Sixty consecutive patients (63.3% men, mean age 47.6 ± 13.3 years) suffering from highly language-eloquent left-hemispheric low- or high-grade glioma underwent preoperative nTMS language mapping and nTMS-based DTI FT, followed by awake surgery for tumor resection. Both nTMS language mapping and DTI FT data were available for resection planning and intraoperative guidance. Clinical outcome parameters, including craniotomy size, extent of resection (EOR), language deficits at different time points, Karnofsky Performance Scale (KPS) score, duration of surgery, and inpatient stay, were assessed.

Results: According to postoperative evaluation, 28.3% of patients showed tumor residuals, whereas new surgery-related permanent language deficits occurred in 8.3% of patients. KPS scores remained unchanged (median preoperative score 90, median follow-up score 90).

Conclusions: This is the first study to present a clinical outcome analysis of this very modern approach, which is increasingly applied in neurooncological centers worldwide. Although human language function is a highly complex and dynamic cortico-subcortical network, the presented approach offers excellent functional and oncological outcomes in patients undergoing surgery of lesions affecting this network.


In modern neurooncology, awake surgery combined with intraoperative direct electrical stimulation (DES) and intraoperative neuromonitoring (IONM) reflects the standard for resection of language-eloquent brain tumors.[19,46,48,61,62] This approach is favored over resection under general anesthesia due to the fact that it allows for language mapping during surgery, which aims to detect and spatially enclose language-related cortical and subcortical structures as an efficient way to reduce postoperative language deficits.[6,46] Within the context of the so-called oncofunctional balance, a minimum rate of postoperative deficits should be achieved in combination with maximum tumor resection, thus ideally leading to optimal postoperative quality of life and prolonged patient survival.[2,10,36,47]

However, the gold standard of awake surgery with DES and IONM can be supported by various preoperative adjuncts that allow for mapping of language function prior to tumor resection, which enables the treating neurosurgeon to assess functionally critical cortical and subcortical structures in advance.[39] Among the most common options in clinical routine, functional MRI (fMRI) and magnetoencephalography (MEG) have been applied successfully.[16,35,39,40,43,44] In addition, navigated transcranial magnetic stimulation (nTMS) has been introduced recently as a novel technique for preoperative language mapping in patients with brain tumors.[42,56,63] By using a magnetic coil, magnetic pulses can be delivered over preselected areas of the scalp of a patient, and these pulses can be spatially related to the respective patient's individual cortical anatomy, thanks to an integrated neuronavigation unit.[45,54] The pulses develop into an electric field that is then capable of stimulating nervous tissue of the brain and can result in transient language disturbances of different kinds when language-related structures are affected by the induced electric field.[18,34,63] Because this approach primarily allows one to parcellate the stimulated cortex into language-positive and language-negative sites, nTMS language mapping has been combined with diffusion tensor imaging fiber tracking (DTI FT) to allow the neurosurgeon to also gain information about subcortical language-related structures.[38,52,55]

The novel approach of nTMS language mapping and nTMS-based DTI FT is increasingly used in specialized neurooncological centers, and standardized mapping protocols and clinical workflow have been established.[30,54] However, the distinct impact of nTMS language mapping on clinical treatment and outcome has only been analyzed in 1 previous study, which did not routinely apply nTMS-based DTI FT in addition to cortical mapping.[53] This earlier study investigated different types of brain tumors but showed that postoperative language deficits were significantly less frequent in patients who underwent preoperative nTMS language mapping when compared to a control group without preoperative nTMS language mapping, and a trend toward fewer unexpected tumor residuals was observed.[53]

Against this background, this study presents the first detailed analysis of using preoperative functional data derived from both nTMS language mapping and nTMS-based DTI FT as an adjunct to awake surgery. The study evaluates the impact of this approach on functional and neurooncological outcome measures among patients suffering from highly language-eloquent gliomas.