Greater extent of resection (EOR) of low-grade gliomas is associated with improved survival. Proximity to eloquent cortical regions often limits resectability and elevates the risk of surgery-related deficits. Therefore, functional localization of eloquent cortex or subcortical fiber tracts can enhance the EOR and functional outcome. Imaging techniques such as functional MRI and diffusion tensor imaging fiber tracking, and neurophysiological methods like navigated transcranial magnetic stimulation and magnetoencephalography, make it possible to identify eloquent areas prior to resective surgery and to tailor indication and surgical approach but also to assess the surgical risk. Intraoperative monitoring with direct cortical stimulation and subcortical stimulation enables surgeons to preserve essential functional tissue during surgery. Through tailored pre- and intraoperative mapping and monitoring the EOR can be maximized, with reduced rates of surgery-related deficits.
Malte Ottenhausen, Sandro M. Krieg, Bernhard Meyer and Florian Ringel
Ehab Shiban, Sandro M. Krieg, Thomas Obermueller, Maria Wostrack, Bernhard Meyer and Florian Ringel
Resection of a motor eloquent lesion has become safer because of intraoperative neurophysiological monitoring (IOM). Stimulation of subcortical motor evoked potentials (scMEPs) is increasingly used to optimize patient safety. So far, scMEP stimulation has been performed intermittently during resection of eloquently located lesions. Authors of the present study assessed the possibility of using a resection instrument for continuous stimulation of scMEPs.
An ultrasonic surgical aspirator was attached to an IOM stimulator and was used as a monopolar subcortical stimulation probe. The effect of the aspirator’s use at different ultrasound power levels (0%, 25%, 50%, 75%, and 100%) on stimulation intensity was examined in a saline bath. Afterward monopolar stimulation with the surgical aspirator was used during the resection of subcortical lesions in the vicinity of the corticospinal tract in 14 patients in comparison with scMEP stimulation via a standard stimulation electrode. During resection, the stimulation current at which an MEP response was still measurable with subcortical stimulation using the surgical aspirator was compared with the corresponding stimulation current needed using a standard monopolar subcortical stimulation probe at the same location.
The use of ultrasound at different energy levels did result in a slight but irrelevant increase in stimulation energy via the tip of the surgical aspirator in the saline bath. Stimulation of scMEPs using the surgical aspirator or monopolar probe was successful and almost identical in all patients. One patient developed a new permanent neurological deficit. Transient new postoperative paresis was observed in 28% (4 of 14) of cases. Gross-total resection was achieved in 64% (9 of 14) cases and subtotal resection (> 80% of tumor mass) in 35% (5 of 14).
Continuous motor mapping using subcortical stimulation via a surgical aspirator, in comparison with the sequential use of a standard monopolar stimulation probe, is a feasible and safe method without any disadvantages. Compared with the standard probe, the aspirator offers continuous information on the distance to the corticospinal tract.
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.
Sandro M. Krieg, Ehab Shiban, Niels Buchmann, Jens Gempt, Annette Foerschler, Bernhard Meyer and Florian Ringel
Navigated transcranial magnetic stimulation (nTMS) is a newly evolving technique. Despite its supposed purpose (for example, preoperative central region mapping), little is known about its accuracy compared with established modalities like direct cortical stimulation (DCS) and functional MR (fMR) imaging. Against this background, the authors performed the current study to compare the accuracy of nTMS with DCS and fMR imaging.
Fourteen patients with tumors in or close to the precentral gyrus were examined using nTMS for motor cortex mapping, as were 12 patients with lesions in the subcortical white matter motor tract. Moreover, preoperative fMR imaging and intraoperative mapping of the motor cortex were performed via DCS, and the outlining of the motor cortex was compared.
In the 14 cases of lesions affecting the precentral gyrus, the primary motor cortex as outlined by nTMS correlated well with that delineated by intraoperative DCS mapping, with a deviation of 4.4 ± 3.4 mm between the two methods. In comparing nTMS with fMR imaging, the deviation between the two methods was much larger: 9.8 ± 8.5 mm for the upper extremity and 14.7 ± 12.4 mm for the lower extremity. In 13 of 14 cases, the surgeon admitted easier identification of the central region because of nTMS. The procedure had a subjectively positive influence on the operative results in 5 cases and was responsible for a changed resection strategy in 2 cases. One of 26 patients experienced nTMS as unpleasant; none found it painful.
Navigated TMS correlates well with DCS as a gold standard despite factors that are supposed to contribute to the inaccuracy of nTMS. Moreover, surgeons have found nTMS to be an additional and helpful modality during the resection of tumors affecting eloquent motor areas, as well as during preoperative planning.
Jens Gempt, Annette Förschler, Niels Buchmann, Haiko Pape, Yu-Mi Ryang, Sandro M. Krieg, Claus Zimmer, Bernhard Meyer and Florian Ringel
The aim of surgical treatment of glioma is the complete resection of tumor tissue with preservation of neurological function. Inclusion of diffusion-weighted imaging (DWI) in the postoperative MRI protocol could improve the delineation of ischemia-associated postoperative neurological deficits. The present study aims to assess the incidence of infarctions following resection of newly diagnosed gliomas in comparison with recurrent gliomas and the influence on neurological function.
Patients who underwent glioma resection for newly diagnosed or recurrent gliomas had early postoperative MRI, including DWI and apparent diffusion coefficient (ADC) maps. Postoperative areas of restricted diffusion were classified as arterial territorial infarctions, terminal branch infarctions, or venous infarctions. Tumor entity, location, and neurological function were recorded.
New postoperative ischemic lesions were identified in 26 (31%) of 84 patients with newly diagnosed gliomas and 20 (80%) of 25 patients with recurrent gliomas (p < 0.01). New permanent and transient neurological deficits were more frequent in patients with recurrent gliomas than in patients with newly diagnosed tumors. Patients with neurological deficits had a significantly higher rate of ischemic lesions.
Postoperative infarctions occur frequently in patients with newly diagnosed and recurrent gliomas and do have an impact on postoperative neurological function. In this patient cohort there was a higher risk for ischemic lesions and for deterioration of neurological function after resection of recurrent tumors. Radiogenic and postoperative tissue changes could contribute to the higher risk of an ischemic infarction in patients with recurrent tumors.
Sandro M. Krieg, Michael Schäffner, Ehab Shiban, Doris Droese, Thomas Obermüller, Jens Gempt, Bernhard Meyer and Florian Ringel
Resection of gliomas in or adjacent to the motor system is widely performed using intraoperative neuromonitoring (IOM). For resection of cerebral metastases in motor-eloquent regions, however, data are sparse and IOM in such cases is not yet widely described. Since recent studies have shown that cerebral metastases infiltrate surrounding brain tissue, this study was undertaken to assess the value and influence of IOM during resection of supratentorial metastases in motor-eloquent regions.
Between 2006 and 2011, the authors resected 206 consecutive supratentorial metastases, including 56 in eloquent motor areas with monitoring of monopolar direct cortically stimulated motor evoked potentials (MEPs). The authors evaluated the relationship between the monitoring data and the course of surgery, clinical data, and postoperative imaging.
Motor evoked potential monitoring was successful in 53 cases (93%). Reduction of MEP amplitude correlated better with postoperative outcomes when the threshold for significant amplitude reduction was set at 80% (only > 80% reduction was considered significant decline) than when it was set at 50% (> 50% amplitude reduction was considered significant decline). Evidence of residual tumor was seen on MR images in 28% of the cases with significant MEP reduction. No residual tumor was seen in any case of stable MEP monitoring. Moreover, preoperative motor deficit, recursive partitioning analysis Class 3, and preoperative radiotherapy were independent risk factors for a new surgery-related motor weakness (occurring in 64% of patients with and 11% of patients without radiotherapy, p > 0.01).
Continuous MEP monitoring provides reliable monitoring of the motor system and also influences the course of operation in resection of cerebral metastases. However, in establishing warning criteria, only an amplitude decline > 80% of the baseline should be considered significant.
Nico Sollmann, Anna Kelm, Sebastian Ille, Axel Schröder, Claus Zimmer, Florian Ringel, Bernhard Meyer and Sandro M. Krieg
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.
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.
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).
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.
Ehab Shiban, Sandro M. Krieg, Bernhard Haller, Niels Buchmann, Thomas Obermueller, Tobias Boeckh-Behrens, Maria Wostrack, Bernhard Meyer and Florian Ringel
Subcortical stimulation is a method used to evaluate the distance from the stimulation site to the corticospinal tract (CST) and to decide whether the resection of an adjacent lesion should be terminated to prevent damage to the CST. However, the correlation between stimulation intensity and distance to the CST has not yet been clearly assessed. The objective of this study was to investigate the appropriate correlation between the subcortical stimulation pattern and the distance to the CST.
Monopolar subcortical motor evoked potential (MEP) mapping was performed in addition to continuous MEP monitoring in 37 consecutive patients with lesions located in motor-eloquent locations. The proximity of the resection cavity to the CST was identified by subcortical MEP mapping. At the end of resection, the point at which an MEP response was still measurable with minimal subcortical MEP intensity was marked with a titanium clip. At this location, different stimulation paradigms were executed with cathodal or anodal stimulation at 0.3-, 0.5-, and 0.7-msec pulse durations. Postoperatively, the distance between the CST as defined by postoperative diffusion tensor imaging fiber tracking and the titanium clip was measured. The correlation between this distance and the subcortical MEP electrical charge was calculated.
Subcortical MEP mapping was successful in all patients. There were no new permanent motor deficits. Transient new postoperative motor deficits were observed in 14% (5/36) of cases. Gross-total resection was achieved in 75% (27/36) and subtotal resection (> 80% of tumor mass) in 25% (9/36) of cases. Stimulation intensity with various pulse durations as well as current intensity was plotted against the measured distance between the CST and the titanium clip on postoperative MRI using diffusion-weighted imaging fiberitracking tractography. Correlational and regression analyses showed a nonlinear correlation between stimulation intensity and the distance to the CST. Cathodal stimulation appeared better suited for subcortical stimulation.
Subcortical MEP mapping is an excellent intraoperative method to determine the distance to the CST during resection of motor-eloquent lesions and is highly capable of further reducing the risk of a new neurological deficit.
Chiara Negwer, Nico Sollmann, Sebastian Ille, Theresa Hauck, Stefanie Maurer, Jan S. Kirschke, Florian Ringel, Bernhard Meyer and Sandro M. Krieg
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.
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.
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).
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.
Jens Gempt, Julia Gerhardt, Vivien Toth, Stefanie Hüttinger, Yu-Mi Ryang, Maria Wostrack, Sandro M. Krieg, Bernhard Meyer, Annette Förschler and Florian Ringel
Brain metastases occur in 10% to 40% of patients harboring cancer. In cases of neurosurgical metastasis resection, all postoperative neurological deterioration should be avoided. Reasons for postoperative deficits can be direct tissue damage due to resection, hemorrhage, venous congestive infarcts, or arterial ischemic events leading to tissue infarction. The aim of this study was to evaluate whether postoperative ischemic infarctions occur in surgery for brain metastasis and to determine their influence on new postoperative neurological deficits.
Patients who underwent resection of brain metastases and had preoperative and early postoperative (within 48 hours) MRI scans, including diffusion-weighted imaging sequences and apparent diffusion coefficient maps, between January 2009 and May 2012 were included in this study. Clinical and histopathological data (histopathological results, pre- and postoperative neurological status, and previous tumor-specific therapy) were recorded.
One hundred twenty-two patients (56 male, 66 female) who underwent resection of brain metastases were included. The patients' mean age was 60 years (range 21–89 years). The mean time span from initial tumor diagnosis to resection of brain metastasis was 44 months (range 0–338 months). The mean preoperative Karnofsky Performance Status was 80% (exact mean 76% ± 17% [SD]), and the mean postoperative value was 80% (exact mean 78% ± 17%). Twelve (9.8%) of the 122 patients had postoperative permanent worsening of a neurological deficit or a new permanent neurological deficit; 44 (36.1%) of the 122 patients had postoperative ischemic lesions. When comparing patients with and without previous brain irradiation, 53.8% of patients with previous brain irradiation had ischemic lesions on postoperative imaging compared with 31.3% of patients without previous brain irradiation (p = 0.033). There was a significant association between ischemia and postoperative neurological status deterioration (transient or permanent); 13 (29.5%) of 44 patients with ischemic lesions had deterioration of their neurological status compared with 7 (9%) of the 78 patients who did not have ischemic lesions (p = 0.003).
This study demonstrates a high prevalence of vascular incidents in patients undergoing resection for metastatic brain disease. Patients harboring postoperative ischemic lesions detected by MRI have a higher rate of neurological deficits (transient or permanent). Patients who had previous irradiation therapy are at higher risk of developing postoperative ischemic lesions. A large number of postoperative neurological deficits are caused by ischemic incidents.