Discovery of Species-Specific Proteotypic Peptides To Establish a Spectral Library Platform for Identification of Nontuberculosis Mycobacteria from Mass Spectrometry-Based Proteomics.

Nontuberculous mycobacteria are opportunistic bacteria pulmonary and extra-pulmonary infections in humans that closely resemble Mycobacterium tuberculosis. Although genome sequencing strategies helped determine NTMs, a common assay for the detection of coinfection by multiple NTMs with M. tuberculosis in the primary attempt of diagnosis is still elusive. Such a lack of efficiency leads to delayed therapy, an inappropriate choice of drugs, drug resistance, disease complications, morbidity, and mortality. Although a high-resolution LC-MS/MS-based multiprotein panel assay can be developed due to its specificity and sensitivity, it needs a library of species-specific peptides as a platform. Toward this, we performed an analysis of proteomes of 9 NTM species with more than 20 million peptide spectrum matches gathered from 26 proteome data sets. Our metaproteomic analyses determined 48,172 species-specific proteotypic peptides across 9 NTMs. Notably, M. smegmatis (26,008), M. abscessus (12,442), M. vaccae (6487), M. fortuitum (1623), M. avium subsp. paratuberculosis (844), M. avium subsp. hominissuis (580), and M. marinum (112) displayed >100 species-specific proteotypic peptides. Finally, these peptides and corresponding spectra have been compiled into a spectral library, FASTA, and JSON formats for future reference and validation in clinical cohorts by the biomedical community for further translation.

Tumor-Specific Alterations in Motor Cortex Excitability and Tractography of the Corticospinal Tract-A Navigated Transcranial Magnetic Stimulation Study.

BACKGROUND: Non-invasive brain mapping using navigated transcranial magnetic stimulation (nTMS) is a valuable tool prior to resection of malignant brain tumors. With nTMS motor mapping, it is additionally possible to analyze the function of the motor system and to evaluate tumor-induced neuroplasticity. Distinct changes in motor cortex excitability induced by certain malignant brain tumors are a focal point of research. METHODS: A retrospective single-center study was conducted involving patients with malignant brain tumors. Clinical data, resting motor threshold (rMT), and nTMS-based tractography were evaluated. The interhemispheric rMT-ratio (rMTTumor/rMTControl) was calculated for each extremity and considered pathological if it was >110% or <90%. Distances between the corticospinal tract and the tumor (lesion-to-tract-distance - LTD) were measured. RESULTS: 49 patients were evaluated. 16 patients (32.7%) had a preoperative motor deficit. The cohort comprised 22 glioblastomas (44.9%), 5 gliomas of Classification of Tumors of the Central Nervous System (CNS WHO) grade 3 (10.2%), 6 gliomas of CNS WHO grade 2 (12.2%) and 16 cerebral metastases (32.7%). 26 (53.1%) had a pathological rMT-ratio for the upper extremity and 35 (71.4%) for the lower extremity. All patients with tumor-induced motor deficits had pathological interhemispheric rMT-ratios, and presence of tumor-induced motor deficits was associated with infiltration of the tumor to the nTMS-positive cortex (p = 0.04) and shorter LTDs (all p < 0.021). Pathological interhemispheric rMT-ratio for the upper extremity was associated with cerebral metastases, but not with gliomas (p = 0.002). CONCLUSIONS: Our study underlines the diagnostic potential of nTMS motor mapping to go beyond surgical risk stratification. Pathological alterations in motor cortex excitability can be measured with nTMS mapping. Pathological cortical excitability was more frequent in cerebral metastases than in gliomas.

Effect of 1,4-Dioxane Solvent on ß-Glucuronidation Using Methyl 1,2,3,4-Tetra-O-acetyl-ß-D-glucuronate as the Glycosyl Donor.

A facile and selective ß-D-glucuronidation of alcohols, such as (-)-menthol, cholestanol, (+)- and (-)-borneols, and 2-adamantanol, using commercially available methyl 1,2,3,4-tetra-O-acetyl-ß-D-glucuronate as the glycosyl donor and trimethylsilyl bis(trifluoromethanesulfonyl)imide (Tf2NTMS) (0.5 equivalent) as the activator in 1,4-dioxane at 60 °C gave products in moderate yields. The addition of MS4A increased the ß : α ratios of D-glucuronides when cholestanol, (+)-borneol, and 2-adamantanol were used as the acceptor substrate.

The in vitro effect of new combinations of carbapenem-ß-lactamase inhibitors for Mycobacterium abscessus.

As new treatment alternatives for Mycobacterium abscessus complex (MABC) are urgently needed, we determined the minimum inhibitory concentrations (MICs) for novel carbapenem combinations, including imipenem-relebactam and tebipenem-avibactam against 98 MABC isolates by broth microdilution. The MIC50 was reduced from 16 to 8 mg/L by adding relebactam to imipenem, while the addition of avibactam to tebipenem showed a more pronounced reduction from 256 to 16 mg/L, representing a promising non-toxic, oral treatment option for further exploration.

Surgical management of Glioma Grade 4: technical update from the neuro-oncology section of the Italian Society of Neurosurgery (SINch®): a systematic review.

PURPOSE: The extent of resection (EOR) is an independent prognostic factor for overall survival (OS) in adult patients with Glioma Grade 4 (GG4). The aim of the neuro-oncology section of the Italian Society of Neurosurgery (SINch®) was to provide a general overview of the current trends and technical tools to reach this goal. METHODS: A systematic review was performed. The results were divided and ordered, by an expert team of surgeons, to assess the Class of Evidence (CE) and Strength of Recommendation (SR) of perioperative drugs management, imaging, surgery, intraoperative imaging, estimation of EOR, surgery at tumor progression and surgery in elderly patients. RESULTS: A total of 352 studies were identified, including 299 retrospective studies and 53 reviews/meta-analysis. The use of Dexamethasone and the avoidance of prophylaxis with anti-seizure medications reached a CE I and SR A. A preoperative imaging standard protocol was defined with CE II and SR B and usefulness of an early postoperative MRI, with CE II and SR B. The EOR was defined the strongest independent risk factor for both OS and tumor recurrence with CE II and SR B. For intraoperative imaging only the use of 5-ALA reached a CE II and SR B. The estimation of EOR was established to be fundamental in planning postoperative adjuvant treatments with CE II and SR B and the stereotactic image-guided brain biopsy to be the procedure of choice when an extensive surgical resection is not feasible (CE II and SR B). CONCLUSIONS: A growing number of evidences evidence support the role of maximal safe resection as primary OS predictor in GG4 patients. The ongoing development of intraoperative techniques for a precise real-time identification of peritumoral functional pathways enables surgeons to maximize EOR minimizing the post-operative morbidity.

Interhemispheric connections in the maintenance of language performance and prognosis prediction: fully connected layer-based deep learning model analysis.

OBJECTIVE: Language-related networks have been recognized in functional maintenance, which has also been considered the mechanism of plasticity and reorganization in patients with cerebral malignant tumors. However, the role of interhemispheric connections (ICs) in language restoration remains unclear at the network level. Navigated transcranial magnetic stimulation (nTMS) and diffusion tensor imaging fiber tracking data were used to identify language-eloquent regions and their corresponding subcortical structures, respectively. METHODS: Preoperative image-based IC networks and nTMS mapping data from 30 patients without preoperative and postoperative aphasia as the nonaphasia group, 30 patients with preoperative and postoperative aphasia as the glioma-induced aphasia (GIA) group, and 30 patients without preoperative aphasia but who developed aphasia after the operation as the surgery-related aphasia group were investigated using fully connected layer-based deep learning (FC-DL) analysis to weight ICs. RESULTS: GIA patients had more weighted ICs than the patients in the other groups. Weighted ICs between the left precuneus and right paracentral lobule, and between the left and right cuneus, were significantly different among these three groups. The FC-DL approach for modeling functional and structural connectivity was also tested for its potential to predict postoperative language levels, and both the achieved sensitivity and specificity were greater than 70%. Weighted IC was reorganized more in GIA patients to compensate for language loss. CONCLUSIONS: The authors' method offers a new perspective to investigate brain structural organization and predict functional prognosis.

Preoperative function-specific connectome analysis predicts surgery-related aphasia after glioma resection.

Glioma resection within language-eloquent regions poses a high risk of surgery-related aphasia (SRA). Preoperative functional mapping by navigated transcranial magnetic stimulation (nTMS) combined with diffusion tensor imaging (DTI) is increasingly used to localize cortical and subcortical language-eloquent areas. This study enrolled 60 nonaphasic patients with left hemispheric perisylvian gliomas to investigate the prediction of SRA based on function-specific connectome network properties under different fractional anisotropy (FA) thresholds. Moreover, we applied a machine learning model for training and cross-validation to predict SRA based on preoperative connectome parameters. Preoperative connectome analysis helps predict SRA development with an accuracy of 73.3% and sensitivity of 78.3%. The current study provides a new perspective of combining nTMS and function-specific connectome analysis applied in a machine learning model to investigate language in neurooncological patients and promises to advance our understanding of the intricate networks.

Elucidating the structural-functional connectome of language in glioma-induced aphasia using nTMS and DTI.

Glioma-induced aphasia (GIA) is frequently observed in patients with newly diagnosed gliomas. Previous studies showed an impact of gliomas not only on local brain regions but also on the functionality and structure of brain networks. The current study used navigated transcranial magnetic stimulation (nTMS) to localize language-related regions and to explore language function at the network level in combination with connectome analysis. Thirty glioma patients without aphasia (NA) and 30 patients with GIA were prospectively enrolled. Tumors were located in the vicinity of arcuate fasciculus-related cortical and subcortical regions. The visualized ratio (VR) of each tract was calculated based on their respective fractional anisotropy (FA) and maximal FA. Using a thresholding method of each tract at 25% VR and 50% VR, DTI-based tractography was performed to construct structural brain networks for graph-based connectome analysis, containing functional data acquired by nTMS. The average degree of left hemispheric networks (Mleft ) was higher in the NA group than in the GIA group for both VR thresholds. Differences of global and local efficiency between 25% and 50% VR thresholds were significantly lower in the NA group than in the GIA group. Aphasia levels correlated with connectome properties in Mleft and networks based on positive nTMS mapping regions (Mpos ). A more substantial relation to language performance was found in Mpos and Mleft compared to the network of negative mapping regions (Mneg ). Gliomas causing deterioration of language are related to various cerebral networks. In NA patients, mainly Mneg was impacted, while Mpos was impacted in GIA patients.

Comparing navigated transcranial magnetic stimulation mapping and "gold standard" direct cortical stimulation mapping in neurosurgery: a systematic review.

The objective of this systematic review is to create an overview of the literature on the comparison of navigated transcranial magnetic stimulation (nTMS) as a mapping tool to the current gold standard, which is (intraoperative) direct cortical stimulation (DCS) mapping. A search in the databases of PubMed, EMBASE, and Web of Science was performed. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and recommendations were used. Thirty-five publications were included in the review, describing a total of 552 patients. All studies concerned either mapping of motor or language function. No comparative data for nTMS and DCS for other neurological functions were found. For motor mapping, the distances between the cortical representation of the different muscle groups identified by nTMS and DCS varied between 2 and 16 mm. Regarding mapping of language function, solely an object naming task was performed in the comparative studies on nTMS and DCS. Sensitivity and specificity ranged from 10 to 100% and 13.3-98%, respectively, when nTMS language mapping was compared with DCS mapping. The positive predictive value (PPV) and negative predictive value (NPV) ranged from 17 to 75% and 57-100% respectively. The available evidence for nTMS as a mapping modality for motor and language function is discussed.

Motor excitability in bilateral moyamoya vasculopathy and the impact of revascularization.

OBJECTIVE: Motor cortical dysfunction has been shown to be reversible in patients with unilateral atherosclerotic disease after cerebral revascularization. Moyamoya vasculopathy (MMV) is a rare bilateral stenoocclusive cerebrovascular disease. The aim of this study was to analyze the corticospinal excitability and the role of bypass surgery in restoring cortical motor function in patients by using navigated transcranial magnetic stimulation (nTMS). METHODS: Patients with bilateral MMV who met the criteria for cerebral revascularization were prospectively included. Corticospinal excitability, cortical representation area, and intracortical inhibition and facilitation were assessed by nTMS for a small hand muscle (first dorsal interosseous) before and after revascularization. The clinically and/or hemodynamically more severely affected hemisphere was operated first as the leading hemisphere. Intra- and interhemispheric differences were analyzed before and after direct or combined revascularization. RESULTS: A total of 30 patients with bilateral MMV were examined by nTMS prior to and after revascularization surgery. The corticospinal excitability was higher in the leading hemisphere compared with the non-leading hemisphere prior to revascularization. This hyperexcitability was normalized after revascularization as demonstrated in the resting motor threshold ratio of the hemispheres (preoperative median 0.97 [IQR 0.89-1.08], postoperative median 1.02 [IQR 0.94-1.22]; relative effect = 0.61, p = 0.03). In paired-pulse paradigms, a tendency for a weaker inhibition of the leading hemisphere was observed compared with the non-leading hemisphere. Importantly, the paired paradigm also demonstrated approximation of excitability patterns between the two hemispheres after surgery. CONCLUSIONS: The study results suggested that, in the case of a bilateral chronic ischemia, a compensation mechanism between both hemispheres seemed to exist that normalized after revascularization surgery. A potential role of nTMS in predicting the efficacy of revascularization must be further assessed.

Provocation and prediction of visual peripersonal neglect-like symptoms in preoperative planning and during awake brain surgery.

Neglect is a severe neuropsychological/neurological deficit that usually develops due to lesions of the posterior inferior parietal area of the right hemisphere and is characterized by a lack of attention to the left side. Our case is a proven right-handed, 30-year-old female patient with a low-grade glioma, which was located in the temporo-opercular region and also in the superior temporal gyrus of the right hemisphere. Upon presurgical planning, the motor, language, and visuospatial functions were mapped. In order to achieve this, the protocol for routine magnetic resonance imaging and navigated transcranial magnetic stimulation has been expanded, accordingly.

Peripheral tetra-cationic Pt(II) porphyrins photo-inactivating rapidly growing mycobacteria: First application in mycobacteriology.

In this manuscript, we report, for the first time, the photoinactivation evaluation of tetra-cationic porphyrins with peripheral Pt (II)-bpy complexes in the photodynamic inactivation (PDI) of rapidly growing mycobacterial strains (RGM). Two different isomeric Pt (II)-porphyrins were synthetized and applied. PDI experiments in the strains of Mycobacteroides abscessus subsp. Abscessus (ATCC 19977), Mycolicibacterium fortuitum (ATCC 6841), Mycobacteroides abscessus subsp. Massiliense (ATCC 48898), and Mycolicibacterium smegmatis (ATCC 700084) conducted with adequate concentration (without aggregation) of photosensitizers (PS) under white-light illumination for 90 min showed that the most effective PS significantly reduced the concentration of viable mycobacteria. The present results show that positively charged porphyrins at the meta position (3-PtTPyP) are more efficient PS against M. abscessus, M. fortuitum, M. massiliense, and M. smegmatis. The effectiveness of the molecule as PS for PDI studies is also clear with mycobacteria, which is strongly related with the porphyrin peripheral charge and coordination platinum (II) compounds and consequently their solubility in physiological media. Tetra-cationic PS may be promising anti-mycobacterial PDI agents with potential applications in medical clinical cases and bioremediation.

NTMS mapping of non-primary motor areas in brain tumour patients and healthy volunteers.

OBJECTIVE: Navigated transcranial magnetic stimulation (nTMS) has been increasingly used for presurgical cortical mapping of the primary motor cortex (M1) but remains controversial for the evaluation of non-primary motor areas (NPMA). This study investigates clinical and neurophysiological parameters in brain tumour patients and healthy volunteers to decide whether single-pulse biphasic nTMS allows to reliably elicite MEP outside from M1 or not. MATERIALS AND METHODS: Twelve brain tumour patients and six healthy volunteers underwent M1 nTMS mapping. NPMA nTMS mapping followed using 120% and 150% M1 resting motor threshold (RMT) stimulation intensity. Spearman's correlation analysis tested the association of clinical and neurophysiological parameters between M1 and NPMA mapping. RESULTS: A total of 88.81% of nTMS stimulations in NPMA in patients/83.87% in healthy volunteers in patients/83.87% in healthy volunteers did not result in MEPs ≥ 50 µV. Positive nTMS mapping in NPMA correlated with higher stimulation intensity and larger M1 areas in patients (120% M1 RMT SI p = 0.005/150% M1 RMT SI p = 0.198). CONCLUSION: Our findings indicate that in case of positive nTMS mapping in NPMA, MEPs originate mostly from M1. For future studies, MEP parameters and TMS coil rotation should be studied closely to assess the risk for postoperative motor deterioration.

Patient-reported experience measures in patients undergoing navigated transcranial magnetic stimulation (nTMS): the introduction of nTMS-PREMs.

BACKGROUND: Patient-reported experience measures (PREMs) are a unique measure of experience of patients which can help address the quality of care of the patients. OBJECTIVE: Our aim of the study is to collect quality of care outcomes with our newly navigated transcranial magnetic stimulation patient-reported experience measure (nTMS-PREMs) questionnaire among neurosurgical patients undergoing nTMS. METHODS: A single-centre prospective nTMS-PREMs 19-item questionnaire study was performed between February 2018 and December 2018 on patient referred for nTMS at our hospital. The Data was analysed using Likert scale, linear and logistic regression using statistical software (STATA 13.0®). RESULTS: Fifty patient questionnaires were collected (30 males, 20 females, mean age of 47.6 ± 2.1 years) among which 74% of patients underwent both motor and language mapping with a mean duration of 103.3 ± 5.1 min. An overall positive response was noted from the results of the questionnaire, tiredness and anxiety being the common effects noted. Patients with the left-sided disease appreciated more the conditions provided in our laboratory (Q4, p = 0.040) and increasing age was related to less confidence and trust (Q6, p = 0.038) in the staff performing the exam. Younger patients tolerated nTMS better than older patients (> 65 years). PubMed literature search resulted in no relevant articles on the use of PREMs in nTMS patients. CONCLUSION: nTMS is a well-tolerated non-invasive tool and nTMS-PREMS provides a promising role in identifying the unmet needs of the patients and improving the quality of their care.

The verb and noun test for peri-operative testing (VAN-POP): standardized language tests for navigated transcranial magnetic stimulation and direct electrical stimulation.

BACKGROUND: Protocols for intraoperative language mapping with direct electrical stimulation (DES) often include various language tasks triggering both nouns and verbs in sentences. Such protocols are not readily available for navigated transcranial magnetic stimulation (nTMS), where only single word object naming is generally used. Here, we present the development, norming, and standardization of the verb and noun test for peri-operative testing (VAN-POP) that measures language skills more extensively. METHODS: The VAN-POP tests noun and verb retrieval in sentence context. Items are marked and balanced for several linguistic factors known to influence word retrieval. The VAN-POP was administered in English, German, and Dutch under conditions that are used for nTMS and DES paradigms. For each language, 30 speakers were tested. RESULTS: At least 50 items per task per language were named fluently and reached a high naming agreement. CONCLUSION: The protocol proved to be suitable for pre- and intraoperative language mapping with nTMS and DES.

Molecular characterization of Mycobacterium abscessus subspecies isolated from patients attending an Italian Cystic Fibrosis Centre.

Mycobacterium abscessus (MABS) infection represents significant management challenge in cystic fibrosis (CF) patients. This retrospective study (2005-2016) aims to determine the prevalence of the subspecies of MABS isolated from CF patients, to evaluate the persistence over the years of a single subspecies of MABS and to correlate mutations responsible for macrolides and amikacin resistance with MIC values. We investigated 314 strains (1 isolate/patient/year) isolated from the lower respiratory tract of 51 chronically infected CF patients. Sequencing of rpoB gene was performed to identify the MABS subspecies. The erm(41) gene was sequenced to differentiate the strains with and without inducible macrolide resistance. Regions of 23S and 16S rRNA were sequenced to investigate mutations responsible for constitutive resistance to macrolides and aminoglycosides, respectively. Antibiotic susceptibility, using commercial microdilution plates, was evaluated according to CLSI. M. abscessus subsp. abscessus accounted for 64% of the isolates, bolletii subspecies for 16% and massiliense subspecies for 20%. All the massiliense strains presented truncated erm(41) gene while 12 abscessus strains presented the mutation T28->C in the erm(41) gene, which makes it inactive. The 23S rRNA analysis did not show constitutive resistance to macrolides in any strain. Mutation of the 16S rRNA gene was highlighted in 2 strains out of 314, in agreement with high MIC values. The correct identification at the subspecies level and the molecular analysis of 23S rRNA, 16S rRNA and erm gene is useful to guide the treatment strategy in patients with M. abscessus lung infection.

Left perisylvian tumor surgery aided by TMS language mapping in a 6-year-old boy: case report.

BACKGROUND: Awake surgery to preserve language function in young children is challenging, therefore reliable non-invasive work-up of language functional anatomy is needed to preserve language function at any cost. Furthermore, there are obvious limitations of an awake craniotomy with direct stimulation on a child. CASE REPORT: A 6-year-old boy with a low-grade glioma of the left temporal lobe suffering from epileptic seizures underwent surgery, guided by preoperative transcranial magnetic stimulation (TMS) language mapping and consecutive DTI fiber tracking. DISCUSSION AND CONCLUSION: We report successful surgery of a language eloquent brain tumor in a young child based on TMS mapping and DTI fiber tracking alone. Surgical treatment of left-sided perisylvian tumors in children is discussed.

When imaging meets neurophysiology: the value of navigated transcranial magnetic stimulation for preoperative neurophysiological mapping prior to brain tumor surgery.

Maximal safe resection is the modern goal for surgery of intrinsic brain tumors located in or close to brain eloquent areas. Nowadays different neuroimaging techniques provide important anatomical and functional information regarding the brain functional organization that can be used to plan a customized surgical strategy to preserve functional networks, and to increase the extent of tumor resection. Among these techniques, navigated transcranial magnetic stimulation (nTMS) has recently gained great favor among the neurosurgical community for preoperative mapping and planning prior to brain tumor surgery. It represents an advanced neuroimaging technique based on the neurophysiological mapping of the functional cortical brain organization. Moreover, it can be combined with other neuroimaging techniques such as diffusion tensor imaging tractography, thus providing a reliable reconstruction of brain eloquent networks. Consequently, nTMS mapping may provide reliable noninvasive brain functional mapping, anticipating information that otherwise may be available to neurosurgeons only in the operating theater by using direct electrical stimulation. The authors describe the reliability and usefulness of the preoperative nTMS-based approach in neurosurgical practice, and briefly discuss their experience using nTMS as well as currently available evidence in the literature supporting its clinical use. In particular, special attention is reserved for the discussion of the role of nTMS as a novel tool for the preoperative neurophysiological mapping of motor and language networks prior to surgery of intrinsic brain tumors located in or close to eloquent networks, as well as for future and promising applications of nTMS in neurosurgical practice.

TMS motor mapping in brain tumor patients: more robust maps with an increased resting motor threshold.

OBJECTIVE: Navigated transcranial magnetic stimulation (nTMS) has found widespread usage across many clinical centers as part of their surgical planning routines. NTMS offers a non-invasive approach to delineation of the motor cortex, in which the region is outlined through electromagnetic stimulation and electromyographic recordings of target muscles. Several neurophysiological parameters such as the motor evoked potential (MEP) and its derivatives, the resting motor threshold (RMT) and motor latency, are collected. The present study investigates the clinical feasibility and reproducibility of increasing the MEP threshold in brain tumor patients, with the goal to improve the robustness of the procedure. MATERIALS AND METHODS: Twenty-three subjects with peri-motor cortex tumors underwent motor mapping with nTMS. RMT was calculated with both conventional 50-µV and experimental 500-µV MEP amplitude thresholds. Motor mapping was performed with 105% of both RMTs stimulator intensity using the FDI as the target muscle. RESULTS: Motor mapping was possible in 20 patients with both the conventional and experimental thresholds. No significant differences in area size were found between motor area maps generated with a conventional 50-µV threshold in comparison to those generated with the higher 500-µV threshold (50 µV 272.56 mm2 [170.47-434.31] vs. 500 µV 240.54 mm2 [169.77-362.84], P = 0.34). Latency time was significantly reduced in 500-µV recordings relative to 50-µV recordings (50 µV 23.38 ms [22.55-24.51] vs. 500 µV 22.57 ms [21.41-23.70], P < 0.001). Both electric field intensity (50 µV 63.81 V/m [54.26-76.11] vs. 500 µV 77.83 V/m [65.21-93.94], P < 0.001) and RMT (50 µV 33 MSO% [28-36] vs. 500 µV 39.5 MSO% [32-44], P < 0.001) were significantly greater with the higher 500-µV threshold. CONCLUSIONS: Our study demonstrates the feasibility of increasing the MEP detection threshold to 500 µV in brain tumor patients for RMT determination and motor area mapping with nTMS.

nTMS guidance of awake surgery for highly eloquent gliomas.

Navigated transcranial magnetic stimulation (nTMS) allows for preoperative mapping for eloquent gliomas. Besides surgical planning, it also guides intraoperative stimulation mapping. The authors' routine includes preoperative nTMS plus nTMS-based tractography for motor and language to consult patients, plan surgery, craniotomy, and guide cortical and subcortical stimulation. Here, the authors present this routine in a 48-year-old woman with a glioma of the left middle and superior frontal gyrus reaching the precentral gyrus and superior longitudinal fascicle. Gross-total resection via awake surgery was achieved without deficit. The nTMS data and nTMS-based tractography augment eloquent glioma management far beyond its current application. The video can be found here: https://youtu.be/h4ldgMXL1ys .