Search Results

You are looking at 1 - 10 of 13 items for

  • Author or Editor: Sandro Krieg x
  • By Author: Sollmann, Nico x
Clear All Modify Search
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.

METHODS

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

In all scenarios, preoperative mapping was considered 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.

Restricted access

Nico Sollmann, Thomas Picht, Jyrki P. Mäkelä, Bernhard Meyer, Florian Ringel and Sandro M. Krieg

Up to now, navigated transcranial magnetic stimulation (nTMS) has been used for motor mapping in the vicinity of rolandic brain lesions. Recently, nTMS has also been suggested to be useful in mapping human language areas.

The authors describe the case of a left-handed patient with a left-side glioblastoma within the opercular inferior frontal gyrus who presented with severe motor aphasia. Preoperative functional MRI (fMRI) indicated speech dominance of the right hemisphere and did not show any language-related activation in the vicinity of the tumor. Navigated TMS, however, showed a significantly higher rate of induced speech arrests for the left than for the right. Left-side direct cortical stimulation induced clear speech arrests during awake surgery.

This case suggests that nTMS may be useful for preoperative speech mapping in tumors affecting the anatomy, vasculature, and brain oxygen levels and therefore impairing fMRI reliability.

Restricted access

Nico Sollmann, Alessia Fratini, Haosu Zhang, Claus Zimmer, Bernhard Meyer and Sandro M. Krieg

OBJECTIVE

Navigated transcranial magnetic stimulation (nTMS) in combination with diffusion tensor imaging fiber tracking (DTI FT) is increasingly used to locate subcortical language-related pathways. The aim of this study was to establish nTMS-based DTI FT for preoperative risk stratification by evaluating associations between lesion-to-tract distances (LTDs) and aphasia and by determining a cut-off LTD value to prevent surgery-related permanent aphasia.

METHODS

Fifty patients with left-hemispheric, language-eloquent brain tumors underwent preoperative nTMS language mapping and nTMS-based DTI FT, followed by tumor resection. nTMS-based DTI FT was performed with a predefined fractional anisotropy (FA) of 0.10, 0.15, 50% of the individual FA threshold (FAT), and 75% FAT (minimum fiber length [FL]: 100 mm). The arcuate fascicle (AF), superior longitudinal fascicle (SLF), inferior longitudinal fascicle (ILF), uncinate fascicle (UC), and frontooccipital fascicle (FoF) were identified in nTMS-based tractography, and minimum LTDs were measured between the lesion and the AF and between the lesion and the closest other subcortical language-related pathway (SLF, ILF, UC, or FoF). LTDs were then associated with the level of aphasia (no/transient or permanent surgery-related aphasia, according to follow-up examinations).

RESULTS

A significant difference in LTDs was observed between patients with no or only surgery-related transient impairment and those who developed surgery-related permanent aphasia with regard to the AF (FA = 0.10, p = 0.0321; FA = 0.15, p = 0.0143; FA = 50% FAT, p = 0.0106) as well as the closest other subcortical language-related pathway (FA = 0.10, p = 0.0182; FA = 0.15, p = 0.0200; FA = 50% FAT, p = 0.0077). Patients with surgery-related permanent aphasia showed the lowest LTDs in relation to these tracts. Thus, LTDs of ≥ 8 mm (AF) and ≥ 11 mm (SLF, ILF, UC, or FoF) were determined as cut-off values for surgery-related permanent aphasia.

CONCLUSIONS

nTMS-based DTI FT of subcortical language-related pathways seems suitable for risk stratification and prediction in patients suffering from language-eloquent brain tumors. Thus, the current role of nTMS-based DTI FT might be expanded, going beyond the level of being a mere tool for surgical planning and resection guidance.

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.

METHODS

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

RESULTS

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

CONCLUSIONS

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

Restricted access

Neal Conway, Noémie Wildschuetz, Tobias Moser, Lucia Bulubas, Nico Sollmann, Noriko Tanigawa, Bernhard Meyer and Sandro M. Krieg

OBJECTIVE

The goal of this study was to obtain a better understanding of the mechanisms underlying cerebral plasticity. Coupled with noninvasive detection of its occurrence, such an understanding has huge potential to improve glioma therapy. The authors aimed to demonstrate the frequency of plastic reshaping, find clues to the patterns behind it, and prove that it can be recognized noninvasively using navigated transcranial magnetic stimulation (nTMS).

METHODS

The authors used nTMS to map cortical motor representation in 22 patients with gliomas affecting the precentral gyrus, preoperatively and 3–42 months postoperatively. Location changes of the primary motor area, defined as hotspots and map centers of gravity, were measured.

RESULTS

Spatial normalization and analysis of hotspots showed an average shift of 5.1 ± 0.9 mm (mean ± SEM) on the mediolateral axis, and 10.7 ± 1.6 mm on the anteroposterior axis. Map centers of gravity were found to have shifted by 4.6 ± 0.8 mm on the mediolateral, and 8.7 ± 1.5 mm on the anteroposterior axis. Motor-eloquent points tended to shift toward the tumor by 4.5 ± 3.6 mm if the lesion was anterior to the rolandic region and by 2.6 ± 3.3 mm if it was located posterior to the rolandic region. Overall, 9 of 16 (56%) patients with high-grade glioma and 3 of 6 (50%) patients with low-grade glioma showed a functional shift > 10 mm at the cortical level.

CONCLUSIONS

Despite the small size of this series, analysis of these data showed that cortical functional reorganization occurs quite frequently. Moreover, nTMS was shown to detect such plastic reorganization noninvasively.

Restricted 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.

METHODS

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.

Restricted access

Nico Sollmann, Noémie Wildschuetz, Anna Kelm, Neal Conway, Tobias Moser, Lucia Bulubas, Jan S. Kirschke, Bernhard Meyer and Sandro M. Krieg

OBJECTIVE

Navigated transcranial magnetic stimulation (nTMS) and diffusion tensor imaging fiber tracking (DTI FT) based on nTMS data are increasingly used for preoperative planning and resection guidance in patients suffering from motor-eloquent brain tumors. The present study explores whether nTMS-based DTI FT can also be used for individual preoperative risk assessment regarding surgery-related motor impairment.

METHODS

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.

Full access

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.

METHODS

Between 2010 and 2013, nTMS motor mapping was performed 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.

Full access

Sebastian Ille, Nico Sollmann, Theresa Hauck, Stefanie Maurer, Noriko Tanigawa, Thomas Obermueller, Chiara Negwer, Doris Droese, Claus Zimmer, Bernhard Meyer, Florian Ringel and Sandro M. Krieg

OBJECT

Repetitive navigated transcranial magnetic stimulation (rTMS) is now increasingly used for preoperative language mapping in patients with lesions in language-related areas of the brain. Yet its correlation with intraoperative direct cortical stimulation (DCS) has to be improved. To increase rTMS's specificity and positive predictive value, the authors aim to provide thresholds for rTMS's positive language areas. Moreover, they propose a protocol for combining rTMS with functional MRI (fMRI) to combine the strength of both methods.

METHODS

The authors performed multimodal language mapping in 35 patients with left-sided perisylvian lesions by using rTMS, fMRI, and DCS. The rTMS mappings were conducted with a picture-to-trigger interval (PTI, time between stimulus presentation and stimulation onset) of either 0 or 300 msec. The error rates (ERs; that is, the number of errors per number of stimulations) were calculated for each region of the cortical parcellation system (CPS). Subsequently, the rTMS mappings were analyzed through different error rate thresholds (ERT; that is, the ER at which a CPS region was defined as language positive in terms of rTMS), and the 2-out-of-3 rule (a stimulation site was defined as language positive in terms of rTMS if at least 2 out of 3 stimulations caused an error). As a second step, the authors combined the results of fMRI and rTMS in a predefined protocol of combined noninvasive mapping. To validate this noninvasive protocol, they correlated its results to DCS during awake surgery.

RESULTS

The analysis by different rTMS ERTs obtained the highest correlation regarding sensitivity and a low rate of false positives for the ERTs of 15%, 20%, 25%, and the 2-out-of-3 rule. However, when comparing the combined fMRI and rTMS results with DCS, the authors observed an overall specificity of 83%, a positive predictive value of 51%, a sensitivity of 98%, and a negative predictive value of 95%.

CONCLUSIONS

In comparison with fMRI, rTMS is a more sensitive but less specific tool for preoperative language mapping than DCS. Moreover, rTMS is most reliable when using ERTs of 15%, 20%, 25%, or the 2-out-of-3 rule and a PTI of 0 msec. Furthermore, the combination of fMRI and rTMS leads to a higher correlation to DCS than both techniques alone, and the presented protocols for combined noninvasive language mapping might play a supportive role in the language-mapping assessment prior to the gold-standard intraoperative DCS.

Full access

Sebastian Ille, Nico Sollmann, Theresa Hauck, Stefanie Maurer, Noriko Tanigawa, Thomas Obermueller, Chiara Negwer, Doris Droese, Tobias Boeckh-Behrens, Bernhard Meyer, Florian Ringel and Sandro M. Krieg

OBJECT

Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is increasingly used and has already replaced functional MRI (fMRI) in some institutions for preoperative mapping of neurosurgical patients. Yet some factors affect the concordance of both methods with direct cortical stimulation (DCS), most likely by lesions affecting cortical oxygenation levels. Therefore, the impairment of the accuracy of rTMS and fMRI was analyzed and compared with DCS during awake surgery in patients with intraparenchymal lesions.

METHODS

Language mapping was performed by DCS, rTMS, and fMRI using an object-naming task in 27 patients with left-sided perisylvian lesions, and the induced language errors of each method were assigned to the cortical parcellation system. Subsequently, the receiver operating characteristics were calculated for rTMS and fMRI and compared with DCS as ground truth for regions with (w/) and without (w/o) the lesion in the mapped regions.

RESULTS

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%).

CONCLUSIONS

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.