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  • Author or Editor: Sebastian Illex
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Sebastian Ille, Jens Gempt, Bernhard Meyer, and Sandro M. Krieg

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.

Free access

Vicki M. Butenschön, Sebastian Ille, Nico Sollmann, Bernhard Meyer, and Sandro M. Krieg

OBJECTIVE

Navigated transcranial magnetic stimulation (nTMS) is used to identify the motor cortex prior to surgery. Yet, there has, until now, been no published evidence on the economic impact of nTMS. This study aims to analyze the cost-effectiveness of nTMS, evaluating the incremental costs of nTMS motor mapping per additional quality-adjusted life year (QALY). By doing so, this study also provides a model allowing for future analysis of general cost-effectiveness of new neuro-oncological treatment options.

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The authors used a microsimulation model based on their cohort population sampled for 1000 patients over the time horizon of 2 years. A health care provider perspective was used to assemble direct costs of total treatment. Transition probabilities and health utilities were based on published literature. Effects were stated in QALYs and established for health state subgroups.

RESULTS

在所有情况下,术前映射是信用卡诈骗罪red cost-effective with a willingness-to-pay threshold < 3*per capita GDP (gross domestic product). The incremental cost-effectiveness ratio (ICER) of nTMS versus no nTMS was 45,086 Euros/QALY. Sensitivity analyses showed robust results with a high impact of total treatment costs and utility of progression-free survival. Comparing the incremental costs caused by nTMS implementation only, the ICER decreased to 1967 Euros/QALY.

CONCLUSIONS

Motor mapping prior to surgery provides a cost-effective tool to improve the clinical outcome and overall survival of high-grade glioma patients in a resource-limited setting. Moreover, the model used in this study can be used in the future to analyze new treatment options in neuro-oncology in terms of their general cost-effectiveness.

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Lea Baumgart, Sebastian Ille, Jan S. Kirschke, Bernhard Meyer, and Sandro M. Krieg

OBJECTIVE

多个解决方案navigation-guided椎弓根crew placement are currently available. Intraoperative imaging techniques are invaluable for spinal surgery, but often there is little attention paid to patient radiation exposure. This study aimed to compare the applied radiation doses of sliding gantry CT (SGCT)– and mobile cone-beam CT (CBCT)–based pedicle screw placement for spinal instrumentation.

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The authors retrospectively analyzed 183 and 54 patients who underwent SGCT- or standard CBCT-based pedicle screw placement, respectively, for spinal instrumentation at their department between June 2019 and January 2020. SGCT uses an automated radiation dose adjustment.

RESULTS

Baseline characteristics, including the number of screws per patient and the number of instrumented levels, did not significantly differ between the two groups. Although the accuracy of screw placement according to Gertzbein-Robbins classification did not differ between the two groups, more screws had to be revised intraoperatively in the CBCT group (SGCT 2.7% vs CBCT 6.0%, p = 0.0036). Mean (± SD) radiation doses for the first (SGCT 484.0 ± 201.1 vs CBCT 687.4 ± 188.5 mGy*cm, p < 0.0001), second (SGCT 515.8 ± 216.3 vs CBCT 658.3 ± 220.1 mGy*cm, p < 0.0001), third (SGCT 531.3 ± 237.5 vs CBCT 641.6 ± 177.3 mGy*cm, p = 0.0140), and total (SGCT 1216.9 ± 699.3 vs CBCT 2000.3 ± 921.0 mGy*cm, p < 0.0001) scans were significantly lower for SGCT. This was also true for radiation doses per scanned level (SGCT 461.9 ± 429.3 vs CBCT 1004.1 ± 905.1 mGy*cm, p < 0.0001) and radiation doses per screw (SGCT 172.6 ± 110.1 vs CBCT 349.6 ± 273.4 mGy*cm, p < 0.0001).

CONCLUSIONS

The applied radiation doses were significantly lower using SGCT for navigated pedicle screw placement in spinal instrumentation. A modern CT scanner on a sliding gantry leads to lower radiation doses, especially through automated 3D radiation dose adjustment.

Free access

Wei Zhang, Sebastian Ille, Maximilian Schwendner, Benedikt Wiestler, Bernhard Meyer, and Sandro M. Krieg

OBJECTIVE

Preoperative fiber tracking (FT) enables visualization of white matter pathways. However, the intraoperative accuracy of preoperative image registration is reduced due to brain shift. Intraoperative FT is currently considered the standard of anatomical accuracy, while intraoperative imaging can also be used to correct and update preoperative data by intraoperative MRI (ioMRI)–based elastic fusion (IBEF). However, the use of intraoperative tractography is restricted due to the need for additional acquisition of diffusion imaging in addition to scanner limitations, quality factors, and setup time. Since IBEF enables compensation for brain shift and updating of preoperative FT, the aim of this study was to compare intraoperative FT with IBEF of preoperative FT.

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Preoperative MRI (pMRI) and ioMRI, both including diffusion tensor imaging (DTI) data, were acquired between February and November 2018. Anatomy-based DTI FT of the corticospinal tract (CST) and the arcuate fascicle (AF) was reconstructed at various fractional anisotropy (FA) values on pMRI and ioMRI, respectively. The intraoperative DTI FT, as a baseline tractography, was fused with original preoperative FT and IBEF-compensated FT, processes referred to as rigid fusion (RF) and elastic fusion (EF), respectively. The spatial overlap index (Dice coefficient [DICE]) and distances of surface points (average surface distance [ASD]) of fused FT before and after IBEF were analyzed and compared in operated and nonoperated hemispheres.

RESULTS

Seventeen patients with supratentorial brain tumors were analyzed. On the operated hemisphere, the overlap index of pre- and intraoperative FT of the CST by DICE significantly increased by 0.09 maximally after IBEF. A significant decrease by 0.5 mm maximally in the fused FT presented by ASD was observed. Similar improvements were found in IBEF-compensated FT, for which AF tractography on the tumor hemispheres increased by 0.03 maximally in DICE and decreased by 1.0 mm in ASD.

CONCLUSIONS

Preoperative tractography after IBEF is comparable to intraoperative tractography and can be a reliable alternative to intraoperative FT.

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Sebastian Ille, Axel Schroeder, Arthur Wagner, Chiara Negwer, Kornelia Kreiser, Bernhard Meyer, and Sandro M. Krieg

OBJECTIVE

Tractography is a useful technique that is standardly applied to visualize subcortical pathways. However, brain shift hampers tractography use during the course of surgery. While intraoperative MRI (ioMRI) has been shown to be beneficial for use in oncology, intraoperative tractography can rarely be performed due to scanner, protocol, or head clamp limitations. Elastic fusion (EF), however, enables adjustment for brain shift of preoperative imaging and even tractography based on intraoperative images. The authors tested the hypothesis that adjustment of tractography by ioMRI-based EF (IBEF) correlates with the results of intraoperative neuromonitoring (IONM) and clinical outcome and is therefore a reliable method.

开云体育世界杯赔率

In 304 consecutive patients treated between June 2018 and March 2020, 8 patients, who made up the basic study cohort, showed an intraoperative loss of motor evoked potentials (MEPs) during motor-eloquent glioma resection for a subcortical lesion within the corticospinal tract (CST) as shown by ioMRI. The authors preoperatively visualized the CST using tractography. Also, IBEFs of pre- and intraoperative images were obtained and the location of the CST was compared in relation to a subcortical lesion. In 11 patients (8 patients with intraoperative loss of MEPs, one of whom also showed loss of MEPs on IBEF evaluation, plus 3 additional patients with loss of MEPs on IBEF evaluation), the authors examined the location of the CST by direct subcortical stimulation (DSCS). The authors defined the IONM results and the functional outcome data as ground truth for analysis.

RESULTS

The maximum mean ± SD correction was 8.8 ± 2.9 (range 3.8–12.0) mm for the whole brain and 5.3 ± 2.4 (range 1.2–8.7) mm for the CST. The CST was located within the lesion before IBEF in 3 cases and after IBEF in all cases (p = 0.0256). All patients with intraoperative loss of MEPs suffered from surgery-related permanent motor deficits. By approximation, the location of the CST after IBEF could be verified by DSCS in 4 cases.

CONCLUSIONS

The present study shows that tractography after IBEF accurately correlates with IONM and patient outcomes and thus demonstrates reliability in this initial study.

Free access

Nico Sollmann, Anna Kelm, Sebastian Ille, Axel Schröder, Claus Zimmer, Florian Ringel, Bernhard Meyer, and Sandro M. Krieg

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.

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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.

Free access

Haosu Zhang, Kartikay Tehlan, Sebastian Ille, Maximilian Schwendner, Zhenyu Gong, Axel Schroeder, Bernhard Meyer, and Sandro M. Krieg

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.

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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.

Free access

Sandro M. Krieg, Denise Bernhard, Sebastian Ille, Bernhard Meyer, Stephanie Combs, Alexander Rotenberg, and Michael C. Frühwald

OBJECTIVE

In adult patients, an increasing group of neurosurgeons specialize entirely in the treatment of highly eloquent tumors, particularly gliomas. In contrast, extensive perioperative neurophysiological workup for pediatric cases has been limited essentially to epilepsy surgery.

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The authors discuss radio-oncological and general oncological considerations based on the current literature and their personal experience.

RESULTS

While several functional mapping modalities facilitate preoperative identification of cortically and subcortically located eloquent areas, not all are suited for children. Direct cortical intraoperative stimulation is impractical in many young patients due to the reduced excitability of the immature cortex. Behavioral requirements also limit the utility of functional MRI and magnetoencephalography in children. In contrast, MRI-derived tractography and navigated transcranial magnetic stimulation are available across ages. Herein, the authors review the oncological rationale of function-guided resection in pediatric gliomas including technical implications such as personalized perioperative neurophysiology, surgical strategies, and limitations.

CONCLUSIONS

综上所述,这些技术,尽管里美tations of some, facilitate the identification of eloquent areas prior to tumor surgery and radiotherapy as well as during follow-up of residual tumors.

Full access

Chiara Negwer, Nico Sollmann, Sebastian Ille, Theresa Hauck, Stefanie Maurer, Jan S. Kirschke, Florian Ringel, Bernhard Meyer, and Sandro M. Krieg

OBJECTIVE

Diffusion tensor imaging (DTI) fiber tracking (FT) has been widely used in glioma surgery in recent years. It can provide helpful information about subcortical structures, especially in patients with eloquent space-occupying lesions. This study compared the newly developed navigated transcranial magnetic stimulation (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.

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Thirty-seven patients with left-sided perisylvian lesions underwent language mapping by repetitive nTMS. 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 (50 mm and 0.2, respectively). Both protocols were performed with standard clinical tractography software.

RESULTS

Both methods visualized language-related fiber tracts (i.e., corticonuclear tract, arcuate fascicle, uncinate fascicle, superior longitudinal fascicle, inferior longitudinal fascicle, arcuate fibers, commissural fibers, corticothalamic fibers, and frontooccipital fascicle) 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).

CONCLUSIONS

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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Lucia Bulubas, Jamil Sabih, Afra Wohlschlaeger, Nico Sollmann, Theresa Hauck, Sebastian Ille, Florian Ringel, Bernhard Meyer, and Sandro M. Krieg

OBJECTIVE

Because of its huge clinical potential, the importance of premotor areas for motor function itself and plastic reshaping due to tumors or ischemic brain lesions has received increased attention. Thus, in this study the authors used navigated transcranial magnetic stimulation (nTMS) to investigate whether tumorous brain lesions induce a change in motor cortex localization in the human brain.

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在2010年至2013年之间,特种加工运动映射性能ormed in a prospective cohort of 100 patients with brain tumors in or adjacent to the rolandic cortex. Spatial data analysis was performed by normalization of the individual motor maps and creation of overlays according to tumor location. Analysis of motor evoked potential (MEP) latencies was performed regarding mean overall latencies and potentially polysynaptic latencies, defined as latencies longer than 1 SD above the mean value. Hemispheric dominance, lesion location, and motor-function deficits were also considered.

RESULTS

Graphical analysis showed that motor areas were not restricted to the precentral gyrus. Instead, they spread widely in the anterior-posterior direction. An analysis of MEP latency showed that mean MEP latencies were shortest in the precentral gyrus and longest in the superior and middle frontal gyri. The percentage of latencies longer than 1 SD differed widely across gyri. The dominant hemisphere showed a greater number of longer latencies than the nondominant hemisphere (p < 0.0001). Moreover, tumor location–dependent changes in distribution of polysynaptic latencies were observed (p = 0.0002). Motor-function deficit did not show any statistically significant effect.

CONCLUSIONS

The distribution of primary and polysynaptic motor areas changes in patients with brain tumors and highly depends on tumor location. Thus, these data should be considered for resection planning.

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