Motor mapping in tumor patients

Schramm, S. et al. Navigated TMS in the ICU: Introducing Motor Mapping to the Critical Care Setting. Brain Sci. 2020, 10(12), 1005


Navigated transcranial magnetic stimulation (nTMS) is a modality for noninvasive cortical mapping. Specifically, nTMS motor mapping is an objective measure of motor function, offering quantitative diagnostic information regardless of subject cooperation or consciousness. Thus far, it has mostly been restricted to the outpatient setting. This study evaluates the feasibility of nTMS motor mapping in the intensive care unit (ICU) setting and solves the challenges encountered in this special environment. We compared neuronavigation based on computed tomography (CT) and magnetic resonance imaging (MRI). We performed motor mappings in neurocritical patients under varying conditions (e.g., sedation or hemicraniectomy). Furthermore, we identified ways of minimizing electromyography (EMG) noise in the interference-rich ICU environment. Motor mapping was performed in 21 patients (six females, median age: 69 years). In 18 patients, motor evoked potentials (MEPs) were obtained. In three patients, MEPs could not be evoked. No adverse reactions occurred. We found CT to offer a comparable neuronavigation to MRI (CT maximum e-field 52 ± 14 V/m vs. MRI maximum e-field 52 ± 11 V/m; p = 0.6574). We detailed EMG noise reduction methods and found that propofol sedation of up to 80 mcg/kg/h did not inhibit MEPs. Yet, nTMS equipment interfered with exposed pulse oximetry. nTMS motor mapping application and use was illustrated in three clinical cases. In conclusion, we present an approach for the safe and reliable use of nTMS motor mapping in the ICU setting and outline possible benefits. Our findings support further studies regarding the clinical value of nTMS in critical care settings.

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Hendrix, P. et al. Preoperative Navigated Transcranial Magnetic Stimulation Improves Gross Total Resection Rates in Patients with Motor-Eloquent High-Grade Gliomas: A Matched Cohort Study. Neurosurgery.2020 Dec 8;nyaa486.


Background: Navigated transcranial magnetic stimulation (nTMS) is an established, noninvasive tool to preoperatively map the motor cortex. Despite encouraging reports from few academic centers with vast nTMS experience, its value for motor-eloquent brain surgery still requires further exploration.

Objective: To further elucidate the role of preoperative nTMS in motor-eloquent brain surgery.

Methods: Patients who underwent surgery for a motor-eloquent supratentorial glioma or metastasis guided by preoperative nTMS were retrospectively reviewed. The nTMS group (n = 105) was pair-matched to controls (non-nTMS group, n = 105). Gross total resection (GTR) and motor outcome were evaluated. Subgroup analyses including survival analysis for WHO III/IV glioma were performed.

Results: GTR was significantly more frequently achieved in the entire nTMS group compared to the non-nTMS group (P = .02). Motor outcome did not differ (P = .344). Bootstrap analysis confirmed these findings. In the metastases subgroup, GTR rates and motor outcomes were equal. In the WHO III/IV glioma subgroup, however, GTR was achieved more frequently in the nTMS group (72.3%) compared to non-nTMS group (53.2%) (P = .049), whereas motor outcomes did not differ (P = .521). In multivariable Cox-regression analysis, prolonged survival in WHO III/IV glioma was significantly associated with achievement of GTR and younger patient age but not nTMS mapping.

Conclusion: Preoperative nTMS improves GTR rates without jeopardizing neurological function. In WHO III/IV glioma surgery, nTMS increases GTR rates that might translate into a beneficial overall survival. The value of nTMS in the setting of a potential survival benefit remains to be determined.

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Lavrador J. et al. Altered Motor Excitability in Patients With Diffuse Gliomas Involving Motor Eloquent Areas: The Impact of Tumor Grading Neurosurgery, nyaa354, September 2020


Diffuse gliomas have an increased biological aggressiveness across the World Health Organization (WHO) grading system. The implications of glioma grading on the primary motor cortex (M1)-corticospinal tract (CST) excitability is unknown.


To assess the excitability of the motor pathway with navigated transcranial magnetic stimulation (nTMS).

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Sollmann N. et. al. Risk Assessment by Presurgical Tractography Using Navigated TMS Maps in Patients with Highly Motor- or Language-Eloquent Brain Tumors, Cancers 2020, 12(5), 1264


Patients with functionally eloquent brain lesions are at risk of functional decline in the course of resection. Given tumor-related plastic reshaping and reallocation of function, individual data are needed for patient counseling and risk assessment prior to surgery. This study evaluates the utility of mapping by navigated transcranial magnetic stimulation (nTMS) and nTMS-based diffusion tensor imaging fiber tracking (DTI FT) for individual risk evaluation of surgery-related decline of motor or language function in the clinical setting. In total, 250 preoperative nTMS mappings (100 language and 150 motor mappings) derived from 216 patients (mean age: 57.0 ± 15.5 years, 58.8% males; glioma World Health Organization (WHO) grade I & II: 4.2%, glioma WHO grade III & IV: 83.4%, arteriovenous malformations: 1.9%, cavernoma: 2.3%, metastasis: 8.2%) were included. Deterministic tractography based on nTMS motor or language maps as seed regions was performed with 25%, 50%, and 75% of the individual fractional anisotropy threshold (FAT). Lesion-to-tract distances (LTDs) were measured between the tumor mass and the corticospinal tract (CST), arcuate fascicle (AF), or other closest language-related tracts. LTDs were compared between patients and correlated to the functional status (no/transient/permanent surgery-related paresis or aphasia). Significant differences were found between patients with no or transient surgery-related deficits and patients with permanent surgery-related deficits regarding LTDs in relation to the CST (p < 0.0001), AF (p ≤ 0.0491), or other closest language-related tracts (p ≤ 0.0435). The cut-off values for surgery-related paresis or aphasia were ≤ 12 mm (LTD—CST) and ≤ 16 mm (LTD—AF) or ≤25 mm (LTD—other closest language-related tract), respectively. Moreover, there were significant associations between the status of surgery-related deficits and the LTD when considering the CST (range r: −0.3994 to −0.3910, p < 0.0001) or AF (range r: −0.2918 to −0.2592, p = 0.0135 and p = 0.0473 for 25% and 50% FAT). In conclusion, this is the largest study evaluating the application of both preoperative functional mapping and function-based tractography for motor and language function for risk stratification in patients with functionally eloquent tumors. The LTD may qualify as a viable marker that can be seamlessly assessed in the clinical neurooncological setup.

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Raffa G. et al. The role of navigated transcranial magnetic stimulation for surgery of motor-eloquent brain tumors: a systematic review and meta-analysis. Clin Neurol Neurosurg. 2019 May;180:7-17. Epub 2019 Mar 5.


Navigated transcranial magnetic stimulation (nTMS) is an emerging tool for surgery of motor-eloquent intrinsic brain tumors, but a critical reappraisal of the literature evidence has never been performed, so far. A systematic review and meta-analysis was performed searching on PubMed/MEDLINE, and the Cochrane Central Register of Controlled Trials for studies that analyzed the impact of nTMS-based motor mapping on surgery of patients affected by motor-eloquent intrinsic brain tumors, in comparison with series of patients operated without using nTMS. The impact of nTMS mapping was assessed analyzing the occurrence of postoperative new permanent motor deficits, the gross total resection rate (GTR), the size of craniotomy and the length of surgery. Only eight studies were considered eligible and were included in the quantitative review and meta-analysis. The pooled analysis showed that nTMS motor mapping significantly reduced the risk of postoperative new permanent motor deficits (OR = 0.54, p = 0.001, data available from eight studies) and increased the GTR rate (OR = 2.32, p < 0.001, data from seven studies). Moreover, data from four studies documented the craniotomy size was reduced in the nTMS group (-6.24 cm2, p < 0.001), whereas a trend towards a reduction, even if non significant, was observed for the length of surgery (-10.30 min, p = 0.38) in three studies. Collectively, currently available literature provides data in favor of the use of nTMS motor mapping: its use seems to be associated with a reduced occurrence of postoperative permanent motor deficits, an increased GTR rate, and a tailored surgical approach compared to standard surgery without using preoperative nTMS mapping. Nonetheless, a growing need of high-level evidence about the use of nTMS motor mapping in brain tumor surgery is perceived. Well-designed randomized controlled studies from multiple Institutions are clearly advocated to continue to shed a light on this emerging topic.

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Krieg SM, et al. Resection of Motor Eloquent Metastases Aided by Preoperative nTMS-Based Motor Maps- Comparison of Two Observational Cohorts. Front Oncol. 2016 Dec 21;6:261.

(Level of Evidence IIb)

A multi-center study at Departments of Neurosurgery at Charite Univärsitetsmedizin, Berlin, Teknische Universität Munchen and University of California San Francisco.

In the study outcomes of brain surgery performed because of tumor metastases in the central brain areas were compared between two observational patient cohorts. Cohort 1 included 120 consecutive patients in whom preoperative localization of the motor cortex in relation to the metastasis was performed with Nexstim NBS device. Cohort 2 included 130 consecutive patients in whom NBS motor mapping was not performed because of organizational issues.

Results in Cohort 1 were significantly better than those in Cohort 2 both in regard to complete tumor removal and likelihood of poor post-operative motor function. Specifically, the NBS mapped patients had a lower rate of residual tumor on postoperative magnetic resonance imaging (odds ratio 0.3025; 95% confidence interval 0.1356-0.6749). Further, surgery-related paresis was less likely in the NBS group (Cohort 1 vs. Cohort 2; patients improved in long-term follow-up: 30.8 vs. 13.1%, unchanged: 65.8 vs. 73.8%, worse: 3.4 vs. 13.1%; p = 0.0002).

In the operating room, the duration of surgery was approximately 30 minutes shorter (Cohort 1: 128.8 ± 49.4 min vs. Cohort 2: 158.0 ± 65.8 min; p = 0.0002) and the surgical skull opening (craniotomy size) 33% smaller (Cohort 1: 16.7 ± 8.6 cm2 vs. Cohort 2: 25.0 ± 17.1 cm2; p < 0.0001) in the NBS mapped patients.

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Picht T et al., Presurgical navigated TMS motor cortex mapping improves outcome in glioblastoma surgery: a controlled observational study. J Neurooncol 2015 Nov 13. [Epub ahead of print]

(Level of Evidence IIb)

A large scale study comparing clinical outcomes of patients with brain tumors near motor eloquent cortex in whom preoperative NBS motor mapping (n=93) was done to outcomes of similar patients in whom NBS mapping could not be done due to logistic/organizational issues (n=34). According to the routine clinical practice at the study institution NBS mapping should have been done to all subjects but due to the institution having its neurosurgical department on two campuses 15km apart from each other and only one NBS system, all patients were not mapped. In other respects patients in both groups received the same medical care (same surgical team and the same operating surgeons, MRI and DTI imaging, the same intraoperative monitoring (IOM) team and practice etc.). The patients in both groups were from the same 3-year time period (2011-2014) ruling out effects of changing clinical practice on any potential differences in outcomes between the groups.

In the group comparison, gross total tumor resection rate was significantly higher in the NBS + IOM group compared to IOM only (61% vs 45%, p<0.05). Further, the degree of tumor resection was also significantly higher in the NBS + IOM group compared to IOM only (85.4% vs 75.9%, p<0.05). In addition, in the NBS+IOM group there were 9 patients (10%) in whom prior to the NBS mapping the surgical plan had been biopsy only (n=3) or tumor debulking only (n=6) due to suspected tumor invasion of motor cortex or pyramidal tracts. NBS mapping and NBS based DTI disproved the suspected invasion and changed the surgical plan to total or subtotal resection.

The mean surgical time tended to be shorter in the NBS + IOM group compared to IOM only (22 min or 9.6%) but the difference between groups was not statistically significant.

There were no differences in motor functional outcomes between the groups indicating that the more extensive resections in the NBS + IOM group compared to IOM only did not come at the expense of increasing adverse events.

The authors state: “This study is the first to prove that the improved surgical outcomes observed in previous studies after the implementation of nTMS to presurgical work-up are not caused by any overall improvement in patient care or a paradigm shift toward more aggressive resection but by the additional functional data provided by nTMS”.

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Krieg S et al., Changing the clinical course of glioma patients by preoperative motor mapping with navigated transcranial magnetic brain stimulation. BMC Cancer. 2015 Apr 8; 15(1):231. [Epub ahead of print]

(Level of evidence III)

A large-scale comparative study on patient outcomes following neurosurgery guided by Navigated Brain Stimulation (NBS) in patients with high-grade glioma. A prospectively enrolled cohort of 70 patients with lesions located in motor eloquent areas were preoperatively mapped by NBS following adoption of the NBS System in 2010. The 70 patients were matched with a control group of 70 patients who had been operated on in 2007- 2010.

On average, the overall size of the craniotomy was significantly smaller for NBS mapped patients when compared to the non-NBS group (25.3 ± 9.7 cm(2) vs. 30.8 ± 13.2 cm(2); p = 0.0058). Furthermore, residual tumor tissue (NBS: 34.3%; non-NBS: 54.3%; p = 0.0172) and unexpected tumor residuals (NBS: 15.7%; non-NBS: 32.9%; p = 0.0180) were less frequent in NBS patients.

Further median inpatient stay was shorter in the NBS group with 12 days for the NBS and 14 days for the non-NBS group (NBS: CI 10.5 - 13.5 days; non-NBS: CI 11.6 - 16.4 days; p = 0.0446). 60.0% of patients of the NBS group and 54.3% of patients of the non-NBS group were eligible for postoperative chemotherapy (OR 1.2630, CI 0.6458 - 2.4710, p = 0.4945), while 67.1% of NBS patients and 48.6% of non-NBS patients received radiotherapy (OR 2.1640, CI 1.0910 - 4.2910, p = 0.0261). Moreover, 3, 6, and 9 months survival was significantly better in the NBS group (p = 0.0298, p = 0.0015, and p = 0.0167).

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Frey D et al., Navigated transcranial magnetic stimulation improves the treatment outcome in patients with brain tumors in motor eloquent locations. Neuro-Oncology 2014; Jun 12. pii: nou110.

(Level of evidence III)

A large-scale comparative study comparing patient outcomes following brain tumor surgery guided by Navigated Brain Stimulation (NBS) to outcomes in patients without NBS functional mapping. A prospectively enrolled cohort of all 250 patients evaluated for surgery for a tumor in a motor eloquent location between May 2007 and October 2012 were preoperatively mapped with NBS following adoption of the NBS System in 2007. The 250 patients were compared with a control group of all 115 patients who met the same in- and exclusion criteria from January 2005 through April 2007, before the availability of NBS mapping at Charité, Berlin.

In the patients mapped with NBS, the mapping results disproved suspected involvement of primary motor cortex in 25.1% of cases, expanded surgical indication in 14.8%, and led to planning of more extensive resection in 35.2% of cases and more restrictive resection in 3.5%. In comparison with the control group, the rate of gross total resections increased significantly from 42% to 59% (P <0.05). Progression-free survival for low grade glioma was significantly better in the nTMS group at 22.4 months than in control group at 15.4 months (P<0.05).

There was no significant difference in postoperative deficits between the groups despite the more extensive resections performed in the NBS mapped patients (rate of postoperative deficits was 8.5% in the control group and 6.1% in the NBS group.

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Krieg SM et al., Preoperative motor mapping by navigated transcranial magnetic brain stimulation improves outcome for motor eloquent lesions. Neuro-Oncology 2014; 0, 1-9, doi: 10.1093/neuonc/nou007

(Level of evidence III)

A large-scale comparative study on patient outcomes following neurosurgery guided by Navigated Brain Stimulation (NBS) in challenging cases. A prospectively enrolled cohort of 100 patients with lesions located in motor eloquent areas were preoperatively mapped by NBS following adoption of the NBS System in 2010. The 100 patients were matched with a control group of 100 patients who had been operated on in the 3 years prior to 2010 – before the availability of NBS mapping at TUM.

The group of patients benefiting from NBS mapping showed a statistically significantly lower rate of residual tumor, as determined by postoperative MRI scanning. On long-term follow-up, 12% of the patients in the NBS group had improved motor function, compared to only 1% of the patients in the control group. Moreover, fewer patients mapped by NBS showed deteriorated motor function postoperatively compared to the control group. With regard to surgical technique, NBS mapping enabled significantly smaller craniotomies.

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Sollmann N, et al. Associations between clinical outcome and navigated transcranial magnetic stimulation characteristics in patients with motor-eloquent brain lesions... J Neurosurg. 2017 Mar 31:1-11.

Sollmann N, et al. Associations between clinical outcome and navigated transcranial magnetic stimulation characteristics in patients with motor-eloquent brain lesions: a combined navigated transcranial magnetic stimulation-diffusion tensor imaging fiber tracking approach.

(Level of evidence III)

Data derived from preoperative nTMS motor mapping and subsequent nTMS-based tractography in 86 patients were analyzed. All patients suffered from high-grade glioma (HGG), low-grade glioma (LGG), or intracranial metastasis (MET). In this context, nTMS-based DTI FT of the corticospinal tract (CST) was performed at a range of fractional anisotropy (FA) levels based on an individualized FA threshold ([FAT]; tracking with 50%, 75%, and 100% FAT), which was defined as the highest FA value allowing for visualization of fibers (100% FAT). Minimum lesion-to-CST distances were measured, and fiber numbers of the reconstructed CST were assessed. These data were then correlated with the preoperative, postoperative, and follow-up status of motor function and the resting motor threshold (rMT). RESULTS At certain FA levels, a statistically significant difference in lesion-to-CST distances was observed between patients with HGG who had no impairment and those who developed surgery-related transient or permanent motor deficits (75% FAT: p = 0.0149; 100% FAT: p = 0.0233). In this context, no patient with a lesion-to-CST distance ≥ 12 mm suffered from any new surgery-related permanent paresis (50% FAT and 75% FAT). Furthermore, comparatively strong negative correlations were observed between the rMT and lesion-to-CST distances of patients with surgery-related transient paresis (Spearman correlation coefficient [rs]; 50% FAT: rs = -0.8660; 75% FAT: rs = -0.8660) or surgery-related permanent paresis (50% FAT: rs = -0.7656; 75% FAT: rs = -0.6763). CONCLUSIONS This is one of the first studies to show a direct correlation between imaging, clinical status, and neurophysiological markers for the integrity of the motor system in patients with brain tumors. The findings suggest that nTMS-based DTI FT might be suitable for individual risk assessment in patients with HGG, in addition to being a surgery-planning tool. Importantly, necessary data for risk assessment were obtained without significant additional efforts, making this approach potentially valuable for direct clinical use.

Pubished in: J Neurosurg. 2017 Mar 31:1-11. doi: 10.3171/2016.11.JNS162322. [Epub ahead of print]

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Moser T, et al. Resection of Navigated Transcranial Magnetic Stimulation-Positive Prerolandic Motor Areas Causes Permanent Impairment of Motor Function. Neurosurgery. 2017 Jul 1;81(1):99-110. doi: 10.1093/neuros/nyw169

(Level of evidence III)

OBJECTIVE: To investigate the resection of nTMS-positive prerolandic motor areas and its correlation with postsurgical impairment of motor function. METHODS: Forty-three patients with rolandic or prerolandic gliomas (WHO grade I-IV) underwent nTMS prior to surgery. Only patients without ischemia within the motor system in postoperative MRI diffusion sequences were enrolled. Based on the 3- dimensional fusion of preoperative nTMS motor mapping data with postsurgical MRI scans, we identified nTMS points that were resected in the infiltration zone of the tumor. We then classified the resected points according to the localization and latency of their motor evoked potentials. Surgery-related paresis was graded as transient (≤6 weeks) or permanent (>6 weeks). RESULTS: Out of 43, 31 patients (72%) showed nTMS-positive motor points in the prerolandic gyri. In general, 13 out of 43 patients (30%) underwent resection of nTMS points. Ten out of these patients showed postoperative paresis. There were 2 (15%) patients with a transient and 8 (62%) with a permanent surgery-related paresis. In 3 cases (23%), motor function remained unimpaired.

CONCLUSION: After resection of nTMS-positive motor points, 62% of patients suffered from a new permanent paresis. Thus, even though they are located in the superior or middle frontal gyrus, these cortical areas must undergo intraoperative mapping.

Takahashi S et al., Navigated transcranial magnetic stimulation for mapping the motor cortex in patients with rolandic brain tumors. Neurosurg Focus, 2013 Apr; 34(4).


A systematic search was used to retrieve 11 reports, published up to October, 2012, in which adult patients were examined with the NBS System prior to surgery. Based on data obtained from 87 patients in 2 studies, the authors found that availability of information from nTMS investigations resulted in a change to the initially proposed surgical strategy, based on anatomical imaging alone, in 25.3% of all patients. The authors concluded that “The nTMS technique spatially correlates well with the gold standard of DES. Its functional information benefits surgical decision making and changes the treatment strategy in one-fourth of cases.”

Picht T, et al., Preoperative Functional Mapping for Rolandic Brain Tumor Surgery: Comparison of Navigated Transcranial Magnetic Stimulation to Direct Cortical Stimulation. Neurosurgery, 2011, 69:581-589.

(Level of evidence IIa)

Controlled trial in 20 patients undergoing surgery for rolandic brain tumors comparing clinical accuracy of non-invasive preoperative navigated transcranial magnetic stimulation to intraoperative direct cortical stimulation. Shows that both methods localize the primary motor cortex to the same gyrus. Authors conclude that nTMS is a reliable tool for preoperative mapping of motor function.

Forster M-T, et al., Navigated Transcranial Magnetic Stimulation and Functional Magnetic Resonance Imaging: Advanced Adjuncts in Preoperative Planning for Central Region Tumors. Neurosurgery, 2011, 68:1317-1325.

(Level of evidence IIa)

Controlled trial in 11 patients undergoing surgery for central region tumors evaluating the reliability of non-invasive preoperative navigated transcranial magnetic stimulation (nTMS) compared with fMRI and intraoperative direct cortical stimulation. Shows that nTMS is more accurate than fMRI when direct cortical stimulation is used a golden standard. Authors conclude that nTMS anticipates information usually only enabled by DCS and therefore allows surgical planning in eloquent cortex surgery.

Coburger J, et al. Comparison of navigated transcranial magnetic stimulation and functional magnetic resonance imaging for preoperative mapping in rolandic tumor surgery. Neurosurg Rev. 2012. Published online Aug 11.

(Level of evidence IIa)

Takahashi S, et al. Plastic relocation of motor cortex in a patient with LGG (low grade glioma) confirmed by NBS (navigated brain stimulation). Acta Neurochir (Wien) 2012, 154(11):2003-8.

(Level of evidence V)

Picht T, et al. The preoperative use of navigated transcranial magnetic stimulation facilitates early resection of suspected low-grade gliomas in the motor cortex. Acta Neurochir (Wien). 2013 Oct; 155(10):1813-21.

(Level of evidence III)

The study aimed to assess what influence preoperative navigated transcranial magnetic stimulation (nTMS) has on the treatment strategy and clinical outcome for suspected low-grade gliomas in presumed motor eloquent location. It was concluded that nTMS provides accurate motor mapping results also in infiltrative gliomas and enables more frequent and more extensive surgical resection of non-enhancing gliomas in or near the primary motor cortex.

Säisänen L, et al. Locating and Outlining the Cortical Motor Representation Areas of Facial Muscles with Navigated Transcranial Magnetic Stimulation. Neurosurgery. 2015 Sep; 77(3):394-405

(Level of evidence IIa)

NBS motor mapping was performed in eight healthy volunteers and 12 patients with brain tumors to localize and outline the cortical representation areas of facial muscles. Mapping was successful in all healthy volunteers and 10 of the 12 patients. The authors conclude that nTMS is an applicable and clinically beneficial noninvasive method to preoperatively map the cortical representation areas of the facial muscles in the lower part of the face.

Methodological validation study of facial muscle motor mapping.

Safety of motor and language mapping

Tarapore P, et al. Safety and Tolerability of Navigated TMS for Preoperative Mapping in Neurosurgical Patients Clin Neurophysiol (2015), doi:

(Level of evidence V)

Authors from 3 institutions (UCSF, San Francisco, Charité, Berlin, TU Munich, München) report their combined experience of safety and tolerability of clinical NBS motor and language mapping in 733 patients with brain tumors. During monopulse stimulation (motor mapping), 5.1% reported discomfort (VAS 1-3), and 0.4% reported pain (VAS >3). During repetitive stimulation (language mapping), 23.4% reported discomfort and 69.5% reported pain. No seizures or other adverse events were observed. The authors conclude that nTMS is safe and well-tolerated in neurosurgical patients.

Motor and language mapping in epilepsy patients

Narayana S, et al, Clinical Applications of Transcranial Magnetic Stimulation in Pediatric Neurology. J Child Neurol. Published online Oct 23.


The authors review the current safety literature on diagnostic single pulse TMS and rTMS for language mapping concluding that these are safe. The authors further provide examples of patient cases where the NBS diagnostics have been performed. The authors further state that they have mapped 70 children with epilepsy and observed only one seizure that seemed to be induced by the clicking coil sound.

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Narayana S, et al. Successful motor mapping with transcranial magnetic stimulation in an infant: A case report. Neurology. 2017 Nov 14;89(20):2115-2117. doi: 10.1212/WNL.0000000000004650. Epub 2017 Oct 11.

(Level of evidence V)

Case report of the youngest patient successfully mapped with NBS.

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Vitikainen A-M, et al., Applicability of nTMS in locating the motor cortical representation areas in patients with epilepsy. Acta Neurochir Epub 2013 Jan 19.

(Level of evidence IIa)

The authors compared the nTMS motor cortical representation maps of hand and arm muscles with the results of invasive electrical cortical stimulation (ECS) in 13 patients with focal epilepsy. The 3D distance between the average nTMS site and average ECS electrode location was 11±4 mm for the hand and 16±7 mm for arm muscle representation areas. In all patients the representation areas defined with nTMS and ECS were located on the same gyrus, also in patients with abundant interictal epileptic activity on the motor gyrus.

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Säisänen L. et al. Non-invasive preoperative localization of primary motor cortex in epilepsy surgery by navigated transcranial magnetic stimulation. Epilepsy Research, 21 Sep 2010, 92(2-3):134-144.

BACKGROUND: Navigated transcranial magnetic stimulation (nTMS) is a non-invasive method to localize the primary motor cortex (M1).

OBJECTIVE/HYPOTHESIS: To assess the safety and feasibility of nTMS as a non-invasive preoperative mode of functional localization of M1 in epilepsy surgery candidates with intractable focal epilepsy due to lesions in the vicinity of M1.

METHODS: We mapped the muscle representation areas of M1 with nTMS in 10 patients (age 2 to 55 years) with intractable epilepsy. The lesions were focal cortical dysplasia (n=6), ganglioglioma (n=2) polymicrogyria (n=1) or dysembryoblastic neuroepithelial tumour (n=1). The optimal stimulation sites and motor threshold (MT) of the distal hand or leg muscles were determined in both hemispheres. Cortical areas were mapped with stimulation intensities 100-120% of the MT to localize functional M1. Patients were on their stabile antiepileptic medication, and EEG was continuously monitored. The clinical benefit obtained with the preoperative nTMS mapping in the surgical decision making was scored as (1) essential, (2) beneficial, or (3) not beneficial, depending mainly on the difference between the functional and the presumed anatomic M1.

RESULTS: The M1 was successfully assessed in all but the 2 youngest patients (aged 2 and 5 years), in whom nTMS was unable to elicit motor responses. nTMS was regarded as essential or beneficial in the localization of M1 in relation to the lesions in 6 out of 10 cases. The optimal motor representation areas were mainly located symmetrically on the precentral gyrus, and corresponded to the presumed location of M1 in MRI. No clinical or EEG evidence of acute epileptogenic adverse effects were observed during the localization procedure. None of the operated patients developed post-operative motor deficits. CONCLUSIONS: nTMS is a safe and feasible clinical tool for the non-invasive preoperative localization of motor cortex in patients with intractable epilepsy due to focal lesions adjacent or within the presumed M1 in MRI.

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Motor and language mapping in patients with vascular malformations

Zdunczyk, A. et al. Functional DTI tractography in brainstem cavernoma surgery. Journal of Neurosurgery. Dec 2020.



Surgical resection of brainstem cavernomas is associated with high postoperative morbidity due to the density of local vulnerable structures. Classical mapping of pathways by diffusion tensor imaging (DTI) has proven to be unspecific and confusing in many cases. In the current study, the authors aimed to establish a more reliable, specific, and objective method for somatotopic visualization of the descending motor pathways with navigated transcranial magnetic stimulation (nTMS)–based DTI fiber tracking.

Twenty-one patients with brainstem cavernomas were examined with nTMS prior to surgery. The resting motor threshold (RMT) and cortical representation areas of hand, leg, and facial function were determined on both hemispheres. Motor evoked potential (MEP)–positive stimulation spots were then set as seed points for tractography. Somatotopic fiber tracking was performed at a fractional anisotropy (FA) value of 75% of the individual FA threshold.


Mapping of the motor cortex and tract reconstruction for hand, leg, and facial function was successful in all patients. The somatotopy of corticospinal and corticonuclear tracts was also clearly depicted on the brainstem level. Higher preoperative RMT values were associated with a postoperative motor deficit (p < 0.05) and correlated with a lower FA threshold (p < 0.05), revealing structural impairment of the corticospinal tract (CST) prior to surgery. In patients with a new deficit, the distance between the lesion and CST was below 1 mm.


nTMS-based fiber tracking enables objective somatotopic tract visualization on the brainstem level and provides a valuable instrument for preoperative planning, intraoperative orientation, and individual risk stratification. nTMS may thus increase the safety of surgical resection of brainstem cavernomas.

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Kato N, et al. Functional brain mapping of patients with arteriovenous malformations using navigated transcranial magnetic stimulation: first experience in ten patients. Acta Neurochir (Wien). 2014 May; 156(5):885-95. doi: 10.1007/s00701-014-2043-7

(Level of evidence V)

A case series of ten patients with unruptured intracranial arteriovenous malformations (AVMs) located in or near eloquent areas in whom preoperative NBS mapping was performed. Motor mapping was conducted for six patients with AVMs near the rolandic region, and speech mapping was performed for four patients with left perisylvian AVMs. After the examination, all patients were treated with surgery, radiosurgery or observed with best medical treatment on case-by-case basis.NBS motor mapping allowed for delineation of the primary motor cortex, even if the anatomy was severely obscured by the AVM in all cases with rolandic AVMs. No plastic relocation of the primary motor cortex was observed. Repetitive stimulation of the left ventral precentral gyrus led to speech impairments in all four cases that underwent speech mapping. Right hemispheric involvement was observed in one out of four cases and potentially indicated plastic changes. No side effects were observed.

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Ille S, et al. The impact of nTMS mapping on treatment of brain AVMs. Acta Neurochir (Wien). 2018 Jan 24. doi: 10.1007/s00701-018-3475-2. [Epub ahead of print]

(Level of evidence III)

The bicentric cohort study aimed to examine the influence of preoperative navigated transcranial magnetic stimulation (nTMS) motor and language mapping data on decision-making for or against surgical treatment of BAVMs.

The influence of data from nTMS on decision-making for or against treatment of BAVMs was examined by confirming/falsifying presumed motor or language eloquence.

The results of nTMS mappings changed the SM grading in nine cases. In six cases, the SM grading changed to a lower grade (= falsified eloquence); in three cases, the SM grading changed to a higher grade due to nTMS mappings (= unexpected eloquence). Out of all 34 cases, indication for surgery was supported by nTMS mappings in 15 cases (7 motors, 8 languages). In six cases, the decision against surgery was made based on nTMS mappings (three motors, three languages).

CONCLUSION: In 21 of 34 cases (62%), nTMS was a supportive argument. nTMS motor and language data can be used for a more objective decision-making regarding the treatment of BAVMs and for a more detailed SM grading regarding the rating of eloquence.

To the Abstract -->

Language mapping

Ille, S. et al. Non-Invasive Mapping for Effective Preoperative Guidance to Approach Highly Language-Eloquent Gliomas—A Large Scale Comparative Cohort Study Using a New Classification for Language Eloquence. Cancers 2021, 13(2), 207


Objective: A considerable number of gliomas require resection via direct electrical stimulation (DES) during awake craniotomy. Likewise, the feasibility of resecting language-eloquent gliomas purely based on navigated repetitive transcranial magnetic stimulation (nrTMS) has been shown. This study analyzes the outcomes after preoperative nrTMS-based and intraoperative DES-based glioma resection in a large cohort. Due to the necessity of making location comparable, a classification for language eloquence for gliomas is introduced.

Methods: Between March 2015 and May 2019, we prospectively enrolled 100 consecutive cases that were resected based on preoperative nrTMS language mapping (nrTMS group), and 47 cases via intraoperative DES mapping during awake craniotomy (awake group) following a standardized clinical workflow. Outcome measures were determined preoperatively, 5 days after surgery, and 3 months after surgery. To make functional eloquence comparable, we developed a classification based on prior publications and clinical experience. Groups and classification scores were correlated with clinical outcomes.

Results: The functional outcome did not differ between groups. Gross total resection was achieved in more cases in the nrTMS group (87%, vs. 72% in the awake group, p = 0.04). Nonetheless, the awake group showed significantly higher scores for eloquence than the nrTMS group (median 7 points; interquartile range 6–8 vs. 5 points; 3–6.75; p < 0.0001). Conclusion: Resecting language-eloquent gliomas purely based on nrTMS data is feasible in a high percentage of cases if the described clinical workflow is followed. Moreover, the proposed classification for language eloquence makes language-eloquent tumors comparable, as shown by its correlation with functional and radiological outcomes.

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Zhang, H. et al. Function-Based Tractography of the Language Network Correlates with Aphasia in Patients with Language-Eloquent Glioblastoma Brain Sci. 2020 Jul 1;10(7):412.


To date, the structural characteristics that distinguish language-involved from non-involved cortical areas are largely unclear. Particularly in patients suffering from language-eloquent brain tumors, reliable mapping of the cortico-subcortical language network is of high clinical importance to prepare and guide safe tumor resection. To investigate differences in structural characteristics between language-positive and language-negative areas, 20 patients (mean age: 63.2 ± 12.9 years, 16 males) diagnosed with language-eloquent left-hemispheric glioblastoma multiforme (GBM) underwent preoperative language mapping by navigated transcranial magnetic stimulation (nTMS) and nTMS-based diffusion tensor imaging fiber tracking (DTI FT). The number of language-positive and language-negative points as well as the gray matter intensity (GMI), normalized volumes of U-fibers, interhemispheric fibers, and fibers projecting to the cerebellum were assessed and compared between language-positive and language-negative nTMS mappings and set in correlation with aphasia grades. We found significantly lower GMI for language-positive nTMS points (5.7 ± 1.7 versus 7.1 ± 1.6, p = 0.0121). Furthermore, language-positive nTMS points were characterized by an enhanced connectivity profile, i.e., these points showed a significantly higher ratio in volumes for U-fibers (p ≤ 0.0056), interhemispheric fibers (p = 0.0494), and fibers projecting to the cerebellum (p = 0.0094). The number of language-positive nTMS points (R ≥ 0.4854, p ≤ 0.0300) as well as the ratio in volumes for U-fibers (R ≤ -0.4899, p ≤ 0.0283) were significantly associated with aphasia grades, as assessed pre- or postoperatively and during follow-up examinations. In conclusion, this study provides evidence for structural differences on cortical and subcortical levels between language-positive and language-negative areas, as detected by nTMS language mapping. The results may further increase confidence in the technique of nTMS language mapping and nTMS-based tractography in the direct clinical setting. Future studies may confirm our results in larger cohorts and may expand the findings to patients with other tumor entities than GBM.

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Ille S, et al. Functional Reorganization of Cortical Language Function in Glioma Patients—A Preliminary Study

Background: Functional reorganization (FR) was shown in glioma patients by direct electrical stimulation (DES) during awake craniotomy. This option for repeated mapping is available in cases of tumor recurrence and after decision for a second surgery. Navigated repetitive transcranial magnetic stimulation (nrTMS) has shown a high correlation with results of DES during awake craniotomy for language-negative sites (LNS) and allows for a non-invasive evaluation of language function. This preliminary study aims to examine FR in glioma patients by nrTMS.

Methods: A cohort of eighteen patients with left-sided perisylvian gliomas underwent preoperative nrTMS language mapping twice. The mean time between mappings was 17 ± 12 months. The cortex was separated into anterior and posterior language-eloquent regions. We defined a tumor area and an area without tumor (WOT). Error rates (ER = number of errors per number of stimulations) and hemispheric dominance ratios (HDR) were calculated as the quotient of the left- and right-sided ER.

Results: In cases in which most language function was located near the tumor during the first mapping, we found significantly more LNS in the tumor area during the second mapping as compared to cases in which function was not located near the tumor (p = 0.049). Patients with seizures showed fewer LNS during the second mapping. We found more changes of cortical language function in patients with a follow-up time of more than 13 months and lower WHO-graded tumors.

Conclusion: Present results confirm that nrTMS can show FR of LNS in glioma patients. Its extent, clinical impact and correlation with DES requires further evaluation but could have a considerable impact in neuro-oncology.

Published: Front Oncol. 2019; 9: 446.

Ille S, et al., Resection of highly language-eloquent brain lesions based purely on rTMS language mapping without awake surgery. Acta Neurochir (Wien). 2016 Dec;158(12):2265-2275

(Level of evidence III)

Case series reporting 4 adult patients with left-sided perisylvian brain lesions suspected to be at risk of language function loss if operated on. Although such patients should be operated using direct cortical stimulation during an awake surgery procedure to minimize the risk, not all patients qualify for awake surgery. In the case series 4 such patients were operated solely based on NBS-language mapping and NBS based DTI. No patient suffered from a new surgery related language deficit 3 months after surgery.

To the Abstract -->

Sollmann N et al., The impact of preoperative language mapping by repetitive navigated transcranial magnetic stimulation on the clinical course of brain tumor patients. BMC Cancer. 2015 Apr 11; 15:261. doi: 10.1186/s12885-015-1299-5.

(Level of evidence III)

A comparative study comparing patient outcomes following brain tumor surgery guided by NBS- NexSpeech language mapping to outcomes in patients without NBS-NexSpeech functional mapping. A prospectively enrolled cohort of all 25 patients evaluated for surgery for a tumor in a speech/language eloquent location between 2013-2014 (GROUP 2) were preoperatively mapped with NBS-NexSpeech. The 25 patients were compared with a control group of 25 patients who met the same in- and exclusion criteria in 2011-2013, but in whom NBS-NexSpeech results were not available for the operating surgeon (GROUP 1).

Mean anterior-posterior (ap) craniotomy extents and overall craniotomy sizes were significantly smaller for the patients in GROUP 2 (Ap: p = 0.0117; overall size: p = 0.0373), and postoperative language deficits were found significantly more frequently for the patients in GROUP 1 (p = 0.0153), although the preoperative language status did not differ between groups (p = 0.7576).

Additionally, there was a trend towards fewer unexpected tumor residuals, shorter surgery duration, less peri- or postoperative complications, shorter inpatient stay, and higher postoperative Karnofsky performance status scale (KPS) for the patients in GROUP 2.

To the abstract -->

Tarapore P, et al. Language Mapping with Navigated Repetitive TMS: Proof of Technique and Validation. NeuroImage (2013), doi: 10.1016/j.neuroimage.2013.05.018

(Level of evidence IIa)

The paper compared non-invasive nrTMS (navigated repetitive TMS), magnetoencephalographic imaging and direct cortical stimulation (DCS) for language mapping in 12 adult patients with lesions around cortical language areas. When compared with intraoperative DCS results, the sensitivity of nTMS was found to be 90%, specificity was 98%, the positive predictive value was 69% and the negative predictive value was 99%. The authors conclude that maps of language function generated with nTMS correlate well with those generated by DCS. Negative nTMS mapping also correlates with negative DCS mapping.

Language mapping using nTMS was found to be safe and well-tolerated. In this study, the clinicians adjusted stimulation intensity to a level each patient found tolerable. Additionally, the investigators used the field navigation-features of the NBS System to avoid stimulating cranial and facial nerves.

In their discussion, the authors propose that, “the real contribution of nTMS is in the preoperative preparation that it allows. By mapping a subject before surgery, the surgeon can generate a precise map of potentially positive language sites, which then may be swiftly interrogated with DCS during surgery.”

To the Abstract -->

Picht, Krieg et al., A Comparison of Language Mapping by Preoperative Navigated Transcranial Magnetic Stimulation and Direct Cortical Stimulation during Awake Surgery. Neurosurgery 2013. Published online Feb 4.

(Level of evidence IIa)

A good overall correlation between repetitive nTMS and DCS was observed, particularly with regard to negatively mapped regions. Non-invasive inhibition mapping with nTMS is evolving as a valuable tool for preoperative mapping of language areas.

To the Abstract -->

Krieg SM, et al. Repeated mapping of cortical language sites by preoperative navigated transcranial magnetic stimulation compared to repeated intraoperative DCS mapping in awake craniotomy. BMC Neurosci. 2014 Jan 30; 15(1):20 doi: 10.1186/1471-2202-15-20.

(Level of evidence IIa)

Three right-handed patients with left-sided gliomas (2 opercular glioblastomas, 1 astrocytoma WHO grade III of the angular gyrus) underwent preoperative language mapping by rTMS as well as intraoperative language mapping provided via direct cortical stimulation (DCS) for initial as well as for repeated Resection 7, 10, and 15 months later. Overall, preoperative rTMS was able to elicit clear language errors in all mappings. A good correlation between initial rTMS and DCS results was observed. As a consequence of brain plasticity, initial DCS and rTMS findings only corresponded with the results obtained during the second examination in one out of three patients thus suggesting changes of language organization in two of our three patients.

Published: BMC Neurosci. 2014 Jan 30; 15(1):20

Vitikainen A, et al. Accelerometer-based automatic voice onset detection in speech mapping with navigated repetitive transcranial magnetic stimulation. J Neurosci Methods. 2015 Sep 30; 253:70-7. doi: 10.1016/j.jneumeth.2015.05.015. Epub 2015 May 28.

(Level of evidence IIa)

The authors describe and present results of an accelerometer-based setup for detection of vocalization- related larynx vibrations combined with an automatic routine for voice onset detection for rTMS speech mapping applying naming. The results produced by the automatic routine were compared with the manually reviewed video-recordings in 12 consecutive patients during preoperative workup for epilepsy or tumor surgery.

The authors found that the automatic routine correctly detected 96% of the voice onsets, resulting in 96% sensitivity and 71% specificity. Majority (63%) of the misdetections were related to visible throat movements, extra voices before the response, or delayed naming of the previous stimuli. The no- response errors were correctly detected in 88% of events. The authors conclude that the setup for automatic detection of voice onsets provides quantitative additional data for analysis of the rTMS- induced speech response modifications. The objectively defined speech response latencies increase the repeatability, reliability and stratification of the rTMS results.

To the Abstract -->

Ille S, et al. Impairment of preoperative language mapping by lesion location: a functional magnetic resonance imaging, navigated transcranial magnetic stimulation, and direct cortical stimulation study.

(Level of evidence IIa)

Accuracy of NBS-rTMS and fMRI based preoperative localization of language cortex was analyzed and compared with DCS during awake surgery in 27 patients with left-sided intraparenchymal perisylvian lesions.

The receiver operating characteristics were calculated for NBS-rTMS and fMRI and compared with DCS as ground truth for regions with (w/) and without (w/o) the lesion in the mapped regions.

The authors found that the w/ subgroup revealed a sensitivity of 100% (w/o 100%), a specificity of 8% (w/o 5%), a positive predictive value of 34% (w/o: 53%), and a negative predictive value (NPV) of 100% (w/o: 100%) for the comparison of rTMS versus DCS.

Findings for the comparison of fMRI versus DCS within the w/ subgroup revealed a sensitivity of 32% (w/o:62%), a specificity of 88% (w/o: 60%), a positive predictive value of 56% (w/o: 62%), and a NPV of 73% (w/o: 60%).

The authors conclude that although strengths and weaknesses exist for both rTMS and fMRI, the results show that rTMS is less affected by a brain lesion than fMRI, especially when performing mapping of language-negative cortical regions based on sensitivity and NPV.

Published in:J Neurosurg. 2015 Aug; 123(2):314-24. doi: 10.3171/2014.10.JNS141582. Epub 2015 Apr 17

DTI in tumor patients

Frey D et al. A new approach for corticospinal tract reconstruction based on navigated transcranial stimulation and standardized fractional anisotropy values. Neuroimage 2012, 62(3):1600-9.

(Level of evidence IIa)

DTI-tracking was performed both using NBS motor mapping results as seed sides and without the information in 50 patients with brain tumors to visualize white matter motor tracts. Tracts obtained with the two methods were compared to each other and the information each method provided for planning of subsequent surgery were compared. NBS-based results changed or modified surgical strategy in 23 of 50 patients (46%), whereas knowledge-based results would have changed surgical strategy in 11 of 50 patients (22%). The authors conclude that fiber tracking based on NBS by the proposed standardized algorithm represents an objective visualization method based on functional data and provides a valuable instrument for preoperative planning and intraoperative orientation and monitoring.

To the abstract -->

Conti A, et al. Navigated Transcranial Magnetic Stimulation for “Somatotopic” Tractography of the Cortico- Spinal Tract. Neurosurgery 2014, DOI: 10.1227/NEU.0000000000000502.

(Level of evidence IIa)

DTI-tracking was performed both using NBS motor mapping results as seed sides and without the information in 20 patients with brain tumors to visualize white matter motor tracts. Tracts obtained with the two methods were compared to each other. NBS-based tractography provided a detailed somatotopic reconstruction of the CST. This NBS-based reconstruction resulted in a decreased number of fibers (305.1 ± 231.7 vs 1024 ± 193, p<0.001) and a significantly greater overlap between the motor cortex and the cortical end-region of the CST compared to the standard technique (90.5 ± 8.8% vs 58.3 ± 16.6%, p < 0.0001). Direct subcortical stimulation confirmed the CST location and the somatotopic reconstruction in all cases. These results suggest that NBS-based tractography of the CST is more accurate and less operator-dependent than the standard technique and provides a reliable anatomical and functional characterization of the motor pathway.

To the abstract -->

Raffa G, et al. The Impact of Diffusion Tensor Imaging Fiber Tracking of the Corticospinal Tract Based on Navigated Transcranial Magnetic Stimulation on Surgery of Motor-Eloquent Brain Lesions.

(Level of evidence IIb)

This retrospective case-control study, reviewed the data of patients operated for suspected motor- eloquent lesions between 2012 and 2015. The patients underwent nTMS mapping of M1 and, from 2014, nTMS-based DTI-FT of the CST. The impact on the preoperative risk/benefit analysis, surgical strategy, craniotomy size, extent of resection (EOR), and outcome were compared with a control group.

35 patients underwent nTMS mapping of M1 (group A), 35 patients also underwent nTMS-based DTI-FT of the CST (group B), and a control group composed of 35 patients treated without nTMS (group C). The patients in groups A and B received smaller craniotomies (P = .01; P = .001), had less postoperative seizures (P = .02), and a better postoperative motor performance (P= .04) and Karnofsky Performance Status (P = .009) than the controls. Group B exhibited an improved risk/benefit analysis (P = .006), an increased EOR of nTMS-negative lesions in absence of preoperative motor deficits (P = .01), and less motor and Karnofsky Performance Status worsening in case of preoperative motor deficits (P = .02, P = .03) than group A. CONCLUSION: nTMS-based mapping enables a tailored surgical approach for motor- eloquent lesions. It may improve the risk/benefit analysis, EOR and outcome, particularly when nTMS- based DTI-FT is performed.

Published in: Neurosurgery. 2017 Nov 29. doi: 10.1093/neuros/nyx554. [Epub ahead of print]

Negwer C, et al., Visualization of subcortical language pathways by diffusion tensor imaging fiber tracking based on rTMS language mapping. Brain Imaging Behav. 2016 Jun 20. [Epub ahead of print]

(Level of evidence III)

The feasibility of using language-related cortical areas identified via repetitive navigated transcranial magnetic stimulation (rTMS) to seed DTI FT of subcortical language tracts was studied. in 37 patients with left-hemispheric perisylvian lesions. Language-positive rTMS stimulation spots were integrated in a deterministic tractography software as objects and used as seed regions for DTI FT.

The rTMS-based DTI FT identified all commonly known subcortical language tracts. The authors conclude that this study proves the feasibility of rTMS-based DTI FT for subcortical language tracts, provides suitable settings, and shows its easy and standardizable application for the visualization of every language tract in 86.5 % of patients.

To the abstract -->

Raffa G, et al., A Novel Technique for Region and Linguistic Specific nTMS-based DTI Fiber Tracking of Language Pathways in Brain Tumor Patients. Front Neurosci. 2016 Dec 2;10:552. eCollection 2016

(Level of evidence III)

Localization of the subcortical language network was performed with 3 methods in 10 patients with brain tumors. The methods were 1) standard anatomy based DTI; 2) DTI using all obtained NBS – language mapping positive cortical locations as the cortical seed site for DTI; and 3) DTI using single NBS-language mapping positive cortical locations as the cortical seed site for DTI. The authors demonstrate the feasibility of the different methods and in this limited size study conclude that method 3 provides the best results.

To the abstract -->

Negwer C, et al., Language pathway tracking: comparing nTMS-based DTI fiber tracking with a cubic ROIs- based protocol. J Neurosurg. 2016 May 27:1-9. [Epub ahead of print]

(Level of evidence IIa)

The study compares nTMS-based DTI FT of language pathways with the most reproducible protocol for language pathway tractography, using cubic regions of interest (ROIs) for the arcuate fascicle in 37 patients with left-sided perisylvian lesions. DTI FT was performed using the cubic ROIs-based protocol and the authors' nTMS-based DTI FT approach. The same minimal fiber length and fractional anisotropy were chosen (50mm and 0.2, respectively). Both protocols were performed with standard clinical tractography software.

Both methods visualized language-related fiber tracts in all 37 patients. Using the cubic ROIs-based protocol, 39.9% of these language-related fiber tracts were detected in the examined patients, as opposed to 76.0% when performing nTMS-based DTI FT. For specifically tracking the arcuate fascicle, however, the cubic ROIs-based approach showed better results (97.3% vs 75.7% with nTMS-based DTI FT).

The authors concluded that the cubic ROIs-based protocol was designed for arcuate fascicle tractography, and this study shows that it is still useful for this intention. However, superior results were obtained using the nTMS-based DTI FT for visualization of other language-related fiber tracts.

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Sollmann N, et al., Interhemispheric connectivity revealed by diffusion tensor imaging fiber tracking derived from navigated transcranial magnetic stimulation maps as a sign of language function at risk in patients with brain tumors.

(Level of evidence IIa)

This study was designed to evaluate whether interhemispheric connectivity (IC) detected by nTMS-based diffusion tensor imaging-fiber tracking (DTI-FT) can be used to predict surgery-related aphasia in patients with brain tumors.

38 patients with left-sided perisylvian brain lesions underwent cortical language mapping of both hemispheres by nTMS prior to awake surgery. Then, nTMS-based DTI-FT was conducted with a fractional anisotropy (FA) of 0.01 and 0.2 to visualize nTMS-based IC. Receiver operating characteristics were calculated for the prediction of a postoperative (irrespective of the preoperative state) and a new surgery-related aphasia by the presence of detectable IC.

RESULTS: Language mapping by nTMS was possible in all patients. Regarding the correlation of aphasia to nTMS-based IC, statistically significant differences were revealed for both evaluated FA values. FA of 0.2 led to a specificity of 93% (postoperative aphasia) and 90% (surgery-related aphasia).

CONCLUSIONS: According to these results, IC detected by preoperative nTMS-based DTI-FT might be regarded as a risk factor for surgery-related aphasia, with a specificity of up to 93%. However, because the majority of enrolled patients suffered from transient aphasia postoperatively, it has to be evaluated whether this approach distinctly leads to similar results among patients with permanent language deficits. Despite this restriction, this approach might contribute to individualized patient consultation prior to tumor resection in clinical practice.

Published in: J Neurosurg. 2016 Apr 1:1-12. [Epub ahead of print]

NBS methodology and case reports

Ruohonen J and Karhu J. Navigated transcranial magnetic stimulation. Neurophysiol Clin 2010, 40(1):7-17.

Review article describing NBS technology and the potential clinical applications of the technology.

Picht T. Current and potential utility of transcranial magnetic stimulation in the diagnostics before brain tumor surgery. CNS Oncol. 2014 Jul; 3(4):299-310. doi: 10.2217/cns.14.25. PubMed PMID: 25286041.

Review article describing utility of NBS technology in pre-neurosurgical planning.

Schmidt S et al, Nonphysiological factors in navigated TMS studies; Confounding covariates and valid intracortical estimates. Hum Brain Mapp. 2014 Aug 29. doi: 10.1002/hbm.22611. [Epub ahead of print]

Method paper demonstrating the accuracy of NBS technology and importance of electric field modeling as performed by Nexstim.

Julkunen P. Methods for estimating cortical motor representation size and location in navigated transcranial magnetic stimulation J Neurosci Methods. 2014 Jul 30; 232:125-33. doi: 10.1016/j.jneumeth.2014.05.020. Epub 2014 May 26.

Method paper on motor mapping.