This work increases the level of evidence for preoperative motor mapping by nTMS for rolandic lesions in a group comparison study. We therefore strongly advocate nTMS to become increasingly used for these lesions. However, a randomized trial on the comparison with the gold standard of intraoperative mapping seems mandatory.

T he resection of tumors within or adjacent to language-eloquent brain regions is still a neurosurgical quest, and a profound presurgical workup is crucial to achieving the best functional and oncological result. 6,71 Today, the most precise way to localize individual language-eloquent regions is direct cortical stimulation (DCS) during awake craniotomy. 9,12,26,44,45,54,62,65,74 Using only DCS, however, we cannot provide the longitudinal abbreviatioNs BOLD = blood oxygen level-dependent; CPS = cortical parcellation system; DCS direct cortical stimulation; ER = error rate; ERT error rate threshold; fMRI = functional MRI; IPI = interpicture interval; NPV = negative predictive value; nTMS navigated TMS; PPV = positive predictive value; PTI = picture-to-trigger interval; RMT = resting motor threshold; ROC = receiver operating characteristic; rTMS repetitive navigated TMS; TMS = transcranial magnetic stimulation. 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...

Since transcranial magnetic stimulation (TMS) was introduced for stimulating the human motor cortex by Barker et al. in 1985, the method has become more sophisticated and was extensively refined.1 PascualLeone and colleagues introduced the term "virtual lesion" and were already in 1991 able to induce speech arrests and counting errors by the use of rapid-rate TMS. 35,36 In the late 1990s and early 2000s, a combination of TMS with optically tracked stereotactic navigation systems was established, whereby it was possible to visualize the stimulation sites via the 3D reconstructed MRI data of the patient's brain. 31,37 Thus, the door to the operating theater was opened since the recorded and analyzed stimulation sites could be used for presurgical planning and data could be abbreviatioNs BOLD = blood-oxygen-level dependent; CPS = cortical parcellation system; DCS = direct cortical stimulation; DTI-FT = diffusion tensor imaging fiber tracking; fMRI = functional MRI; NPV = negative predictive value; PPV = positive predictive value; PTI = picture-to-trigger interval; RMT = resting motor threshold; ROC = receiver operating characteristic; rTMS = repetitive navigated TMS; TMS = 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.

BackgroundMapping of the motor cortex by navigated transcranial magnetic stimulation (nTMS) can be used for preoperative planning in brain tumor patients. Just recently, it has been proven to actually change outcomes by increasing the rate of gross total resection (GTR) and by reducing the surgery-related rate of paresis significantly in cohorts of patients suffering from different entities of intracranial lesions. Yet, we also need data that shows whether these changes also lead to a changed clinical course, and can also be achieved specifically in high-grade glioma (HGG) patients.MethodsWe prospectively enrolled 70 patients with supratentorial motor eloquently located HGG undergoing preoperative nTMS (2010–2014) and matched these patients with 70 HGG patients who did not undergo preoperative nTMS (2007–2010).ResultsOn average, the overall size of the craniotomy was significantly smaller for nTMS patients when compared to the non-nTMS group (nTMS: 25.3 ± 9.7 cm2; non-nTMS: 30.8 ± 13.2 cm2; p = 0.0058). Furthermore, residual tumor tissue (nTMS: 34.3%; non-nTMS: 54.3%; p = 0.0172) and unexpected tumor residuals (nTMS: 15.7%; non-nTMS: 32.9%; p = 0.0180) were less frequent in nTMS patients. Regarding the further clinical course, median inpatient stay was 12 days for the nTMS and 14 days for the non-nTMS group (nTMS: CI 10.5 – 13.5 days; non-nTMS: CI 11.6 – 16.4 days; p = 0.0446). 60.0% of patients of the nTMS group and 54.3% of patients of the non-nTMS group were eligible for postoperative chemotherapy (OR 1.2630, CI 0.6458 – 2.4710, p = 0.4945), while 67.1% of nTMS patients and 48.6% of non-nTMS 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 nTMS group (p = 0.0298, p = 0.0015, and p = 0.0167).ConclusionsWith the limitations of this study in mind, our data show that HGG patients might benefit from preoperative nTMS mapping.

T he aim of surgery for primary and secondary intrinsic brain tumors is complete tumor resection to improve prognosis and control symptoms, and thereby improve the patient's quality of life. 24,39,45,47 However, the goal of maximum resection should be met without any new surgery-related neurological deficits arising, 13 and all efforts should be made to reduce patients' risk for neurological damage. Therefore, lesions in or near motor-eloquent regions, such as the precentral gyrus or the corticospinal tract (CST), represent particularly difficult situations in neurosurgery, and precautions need to be taken to prevent postoperative damage while maximizing resection.Intraoperative electrophysiological mapping and monitoring of the motor cortex and subcortical pyramidal tract obJect 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. methods 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. results 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. coNclusioNs 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 reduc...

BackgroundWhen treating cerebral metastases all involved multidisciplinary oncological specialists have to cooperate closely to provide the best care for these patients. For the resection of brain metastasis several studies reported a considerable risk of new postoperative paresis. Pre- and perioperative chemotherapy (Ctx) or radiotherapy (Rtx) alter vasculature and adjacent fiber tracts on the one hand, and many patients already present with paresis prior to surgery on the other hand. As such factors were repeatedly considered risk factors for perioperative complications, we designed this study to also identify risk factors for brain metastases resection.MethodsBetween 2006 and 2011, we resected 206 brain metastases consecutively, 56 in eloquent motor areas and 150 in non-eloquent ones. We evaluated the influences of preoperative paresis, previous Rtx or Ctx as well as recursive partitioning analysis (RPA) class on postoperative outcome.ResultsIn general, 8.7% of all patients postoperatively developed a new permanent paresis. In contrast to preoperative Ctx, previous Rtx as a single or combined treatment strategy was a significant risk factor for postoperative motor weakness. This risk was even increased in perirolandic and rolandic lesions. Our data show significantly increased risk of new deficits for patients assigned to RPA class 3. Even in non-eloquently located brain metastases the risk of new postoperative paresis has not to be underestimated. Despite the microsurgical approach, our cohort shows a high rate of unexpected residual tumors in postoperative MRI, which supports recent data on brain metastases’ infiltrative nature but might also be the result of our strict study protocol.ConclusionsSurgical resection is a safe treatment of brain metastases. However, preoperative Rtx and RPA score 3 have to be taken into account when surgical resection is considered.

C ontinuous motor evoked potential (MEP) monitoring via direct cortical or transcranial stimulation is an established method of neuromonitoring during the resection of lesions in or near the corticospinal tract (CST). 3,8,9,14,18,21,22 Subcortical MEP (scMEP) stimulation is an additional intraoperative neurophysiological monitoring (IOM) tool, which is very helpful in assessing the proximity of the stimulation point to the CST. Thus, it supports the surgeon in determining where the resection should be stopped to avoid injury to the CST. 3,4,7,12,13,15,18,19,21,22,26 However, the use of scMEP stimulation has always involved an interruption in the resection, a change to a handheld stimulation probe for mapping the resection borders. Therefore, a balance between safety (frequent halting of the resection and changing the instruments for mapping) and a continuous resective workflow (infrequent changing of the instruments for mapping) was necessary. Using a resective instrument as a stimulation probe would be ideal to enhance the workflow and safety of resections close to the CST.In the present study we describe an approach in which abbreviatioNs CST = corticospinal tract; DTI = diffusion tensor imaging; IOM = intraoperative neurophysiological monitoring; MEP = motor evoked potential; scMEP = subcortical MEP. obJect 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. methods 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. results 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 mono polar 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. Grosstot...

BackgroundRepetitive navigated transcranial magnetic stimulation (rTMS) in combination with object naming is able to elicit naming errors by stimulating language-related brain regions. However, stimulation results mainly depend on coil positioning and stimulation parameters, which have not been investigated since the implementation of neuronavigation to transcranial magnetic stimulation. Therefore, the following three parameters were systematically examined in the present study: coil angulation, stimulation frequency, and stimulation intensity.MethodsFive healthy, right-handed subjects underwent rTMS language mapping of Broca’s as well as Wernicke’s areas of the left hemisphere. During mapping sessions, coil angulation was changed clockwise in 45° steps, and the stimulation frequency and intensity were varied within a considerably wide range. For angulation, the anterior-posterior (ap) coil orientation was used as reference position.ResultsAn angulation of 90° to ap coil orientation led to the highest rate of naming errors within Broca’s area, whereas an inhomogeneous distribution of angulations was observed during stimulation of Wernicke’s area. Therefore, ap coil orientation, which is regarded as standard in rTMS language mapping, could not be approved as the optimal position. With regard to stimulation parameters, 20 Hz and 120% of the resting motor threshold (RMT) were defined as optimal.ConclusionsCoil angulation, stimulation frequency, and stimulation intensity have significant impacts on language impairment during rTMS mapping. The variation of only one of these parameters already leads to a clearer disruption of language performance. Therefore, individually adapted stimulation protocols have to be determined prior to language mapping in order to improve mapping results.