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.