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Background: Functional reorganization (FR) was shown in glioma patients by direct electrical stimulation (DES) during awake craniotomy. This option for repeated mapping is available in cases of tumor recurrence and after decision for a second surgery. Navigated repetitive transcranial magnetic stimulation (nrTMS) has shown a high correlation with results of DES during awake craniotomy for language-negative sites (LNS) and allows for a non-invasive evaluation of language function. This preliminary study aims to examine FR in glioma patients by nrTMS. Methods: A cohort of eighteen patients with left-sided perisylvian gliomas underwent preoperative nrTMS language mapping twice. The mean time between mappings was 17 ± 12 months. The cortex was separated into anterior and posterior language-eloquent regions. We defined a tumor area and an area without tumor (WOT). Error rates (ER = number of errors per number of stimulations) and hemispheric dominance ratios (HDR) were calculated as the quotient of the left- and right-sided ER. Results: In cases in which most language function was located near the tumor during the first mapping, we found significantly more LNS in the tumor area during the second mapping as compared to cases in which function was not located near the tumor ( p = 0.049). Patients with seizures showed fewer LNS during the second mapping. We found more changes of cortical language function in patients with a follow-up time of more than 13 months and lower WHO-graded tumors. Conclusion: Present results confirm that nrTMS can show FR of LNS in glioma patients. Its extent, clinical impact and correlation with DES requires further evaluation but could have a considerable impact in neuro-oncology.

Object: As various recent studies show, damage to white matter pathways leads to permanent functional deficits in a high percentage of patients. Particularly the subcortical language network is complex, and its visualization has a tremendous relevance for neurosurgeons. This pilot study aims to correlate language-eloquent white matter pathways with the course of language function after the resection of left-sided perisylvian gliomas. Methods: We included 10 patients who underwent resection of highly language-eloquent high- (9 pts) and low-grade gliomas (1 pts). We performed navigated repetitive transcranial magnetic stimulation (nrTMS)-based tractography via diffusion tensor imaging fiber trackings (DTI FT) preoperatively (PRE-1), postoperatively (POST-1), and at long-term follow up or tumor recurrence (PRE-2). We separately tracked the inferior fronto-occipital fascicle (IFOF), the frontal aslant tract (FAT), and the superior longitudinal (SLF), and arcuate fascicle (AF), and correlated the amount of visualized fibers to the patients' language function at each date. Results: The changes of nrTMS-based DTI FTs of single white matter pathways correlated with the according status of language function for any of the pathways in 80% of patients and in 19 of 30 (63%) single pathway comparisons between PRE-1 and POST-1. Between POST-1 and PRE-2 the nrTMS-based DTI FTs correlated with the status of language function for any of the pathways in all patients and in 24 of 30 (80%) single pathway comparisons. Single FT results correlated with the according status of language function at POST-1 in 60, 70, and 60% of cases, and with the according status of language function at PRE-2 in 60, 90, and 90% of cases for the tracking of the IFOF, FAT, and SLF/AF, respectively. Conclusion: By the present results we were able to show that nrTMS-based DTI FT of the IFOF, FAT, and SLF/AF mainly correlates with the according status of language function preoperatively, postoperatively, and at long-term follow up after the resection of left-sided perisylvian gliomas.

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 .

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.

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.

Background: Preserving functionality is important during neurosurgical resection of brain tumors. Specialized centers also map further brain functions apart from motor and language functions, such as arithmetic processing (AP). The mapping of AP by navigated repetitive transcranial magnetic stimulation (nrTMS) in healthy volunteers has been reported., Objective: The present study aimed to correlate the results of mapping AP with functional patient outcomes., Methods: We included 26 patients with parietal brain tumors. Because of preoperative impairment of AP, mapping was not possible in 8 patients (31%). We stimulated 52 cortical sites by nrTMS while patients performed a calculation task. Preoperatively and postoperatively, patients underwent a standardized number-processing and calculation test (NPCT). Tumor resection was blinded to nrTMS results, and the change in NPCT performance was correlated to resected AP-positive spots as identified by nrTMS., Results: The resection of AP-positive sites correlated with a worsening of the postoperative NPCT result in 12 cases. In 3 cases, no AP-positive sites were resected and the postoperative NPCT result was similar to or better than preoperatively. Also, in 3 cases, the postoperative NPCT result was better than preoperatively, although AP-positive sites were resected., Conclusions: Despite presenting only a few cases, nrTMS might be a useful tool for preoperative mapping of AP. However, the reliability of the present results has to be evaluated in a larger series and by intraoperative mapping data., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Within language function research, there is a shift of focus from cortical specialization to a more hodotopical view including subcortical fiber tracts in functional and oncologic considerations. Diffusion tensor imaging fiber tracking (DTI FT) is well established to visualize subcortical fiber tracts. Recently, a new technique has been developed using cortical regions mapped via repetitive navigated transcranial magnetic stimulation (rTMS) as seed regions. This study investigates if rTMS-based DTI FT for language pathways is also feasible postoperatively and whether preoperative versus postoperative fiber changes correlate with changes and severity of the patients' aphasia grades., Methods: rTMS-based DTI FT was performed preoperatively and postoperatively in 24 patients with left hemispheric perisylvian tumors. Language pathways were analyzed individually preoperatively and postoperatively with 5 different settings of minimum fiber length and fractional anisotropy. Transient aphasia was defined as any new or worse language impairment caused by surgery that resolved within the regular 3-month follow-up interval. Because postoperative aphasia does not allow rTMS language mapping, preoperative rTMS data were used throughout., Results: Patients with transient aphasia postoperatively had a significant reduction in fiber count compared with patients without deficit (321.5 ± 242.8 fibers vs. 518.0 ± 435.2 fibers; P = 0.01). Furthermore, in this patient group, the arcuate fascicle was lost postoperatively twice as often compared with patients with no deficit after surgery (52% vs. 26%; P < 0.01)., Conclusions: This study shows that rTMS-based DTI FT is feasible for postoperative examination of language pathways. Moreover, changes in preoperative versus postoperative fibers correlate well with the grade of aphasia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The treatment of brain arteriovenous malformations (BAVMs) is still contrarily discussed. Despite the debatable results of the ARUBA trial, most BAVMs still require treatment depending on the Spetzler-Martin (SM) grading. Since size is measurable and venous drainage is visible, the determination of eloquence is comparably crucial but not fully objective. The present bicentric cohort study aims to examine the influence of preoperative navigated transcranial magnetic stimulation (nTMS) motor and language mapping data on decision-making for or against surgical treatment of BAVMs., Methods: The influence of data from nTMS on decision-making for or against treatment of BAVMs was examined by confirming/falsifying presumed motor or language eloquence., Results: The results of nTMS mappings changed the SM grading in nine cases. In six cases, the SM grading changed to a lower grade (= falsified eloquence); in three cases, the SM grading changed to a higher grade due to nTMS mappings (= unexpected eloquence). Out of all 34 cases, indication for surgery was supported by nTMS mappings in 15 cases (7 motors, 8 languages). In six cases, the decision against surgery was made based on nTMS mappings (three motors, three languages)., Conclusion: In 21 of 34 cases (62%), nTMS was a supportive argument. We could show that nTMS motor and language data can be used for a more objective decision-making regarding the treatment of BAVMs and for a more detailed SM grading regarding the rating of eloquence.

Background: During awake craniotomy for tumor resection, a neuropsychologist (NP) is regarded as a highly valuable partner for neurosurgeons. However, some centers do not routinely involve an NP, and data to support the high influence of the NP on the perioperative course of patients are mostly lacking., Objective: The aim of this study was to investigate whether there is a difference in clinical outcomes between patients who underwent awake craniotomy with and without the attendance of an NP., Methods: Our analysis included 61 patients, all operated on for resection of a presumably language-eloquent glioma during an awake procedure. Of these 61 cases, 47 surgeries were done with neuropsychological support (NP group), whereas 14 surgeries were performed without an NP (non-NP group) due to a language barrier between the NP and the patient. For these patients, neuropsychological assessment was provided by a bilingual resident., Results: Both groups were highly comparable regarding age, gender, preoperative language function, and tumor grades (glioma WHO grades 1-4). Gross total resection (GTR) was achieved more frequently in the NP group (NP vs. non-NP: 61.7 vs. 28.6%, P  = 0.04), which also had shorter durations of surgery (NP vs. non-NP: 240.7 ± 45.7 vs. 286.6 ± 54.8 min, P  < 0.01). Furthermore, the rate of unexpected tumor residuals (estimation of the intraoperative extent of resection vs. postoperative imaging) was lower in the NP group (NP vs. non-NP: 19.1 vs. 42.9%, P  = 0.09), but no difference was observed in terms of permanent surgery-related language deterioration (NP vs. non-NP: 6.4 vs. 14.3%, P  = 0.48)., Conclusion: We need professional neuropsychological evaluation during awake craniotomies for removal of presumably language-eloquent gliomas. Although these procedures are routinely carried out with an NP, this is one of the first studies to provide data supporting the NP's crucial role. Despite the small group size, our study shows statistically significant results, with higher rates of GTR and shorter durations of surgery among patients of the NP group. Moreover, our data emphasize the common problem of language barriers between the surgical and neuropsychological team and patients requiring awake tumor resection.

Human language organization models and language time course patterns are still predominantly derived from meta-analyses of numerous single publications, which only investigated scattered cortical regions. Moreover, there is not much literature available on the exact impact of repetitive navigated transcranial magnetic stimulation (rTMS) onset times on object naming. We, therefore, used a virtual lesion-based approach by mapping various cortical areas with rTMS to investigate the time course of object naming, and to specifically provide data on the pattern of rTMS language mapping results depending on different stimulation onset times. Ten healthy, right-handed subjects were enrolled, and rTMS in combination with an object-naming task was performed with different stimulation onset times (0 ms, 100 ms, 200 ms, 300 ms, 400 ms, and 500 ms). Subsequent to language mapping, all naming errors detected were systematically classified with respect to previous literature. The majority of errors was elicited within the opercular inferior frontal gyrus (opIFG) and ventral precentral gyrus (vPrG), and the spatial distribution of naming errors changed according to the time point of naming disruption by varying onset times. For instance, immediate rTMS onset led to a widespread cortical distribution of no responses, whereas performance and hesitation errors increased with higher stimulation onset times.

Diffusion tensor imaging fiber tracking (DTI FT) is used to visualize subcortical fiber tracts. Yet, there is no standard at hand to visualize language-involved subcortical fibers reliably. Thus, this study investigates the feasibility of using language-related cortical areas identified via repetitive navigated transcranial magnetic stimulation (rTMS) to seed DTI FT of subcortical language tracts. From 2011 to 2014, 37 patients with left-hemispheric perisylvian lesions were examined. Language-positive rTMS stimulation spots were integrated in the deterministic tractography software (BrainLAB, iPlanNet 3.0) as objects and used as seed regions for DTI FT. Tractography was then performed in each patient with 77 different combinations of fiber lengths (40 - 100 mm) and fractional anisotropy (FA; 0.01 - 0.5). The rTMS-based DTI FT identified all commonly known subcortical language tracts, such as the corticonuclear tract, arcuate fascicle, uncinate fascicle, superior longitudinal fascicle, inferior longitudinal fascicle, arcuate fibers, commissural fibers, corticothalamic fibers, and the fronto-occipital fascicle. In 32 patients (86.5 %), each above-named tract could be visualized, while at least 6 out of these 9 tracts were identified in each patient. A fiber length of 100 mm and an FA of 0.1 or 0.15 provided optimal visualization by revealing 125 and 61 individually tracked fibers per visualized language tract and 90 % and 73 % of all language-related tracts, respectively. This study proves the feasibility of rTMS-based DTI FT for subcortical language tracts, provides suitable settings, and shows its easy and standardizable application for the visualization of every language tract in 86.5 % of patients.

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.

Background: Besides motor and language function, tumor resections within the frontal and parietal lobe have also been reported to cause neuropsychological impairment like prosopagnosia. Objective: Since non-navigated transcranial magnetic stimulation (TMS) has previously been used to map neuropsychological cortical function, this study aims to evaluate the feasibility and spatial discrimination of repetitive navigated TMS (rTMS) mapping for detection of face processing impairment in healthy volunteers. The study was also designed to establish this examination for preoperative mapping in brain tumor patients. Methods: Twenty healthy and purely right-handed volunteers (11 female, 9 male) underwent rTMS mapping for cortical face processing function using 5 Hz/10 pulses. Both hemispheres were investigated randomly with an interval of 2 weeks between mapping sessions. Fifty-two predetermined cortical spots of the whole hemispheres were mapped after baseline measurement. The task consisted of 80 portraits of popular persons, which had to be named while rTMS was applied. Results: In 80% of all subjects rTMS elicited naming errors in the right middle middle frontal gyrus (mMFG). Concerning anomia errors, the highest error rate (35%) was achieved in the bilateral triangular inferior frontal gyrus (trIFG). With regard to similarly or wrongly named persons, we observed 10% error rates mainly in the bilateral frontal lobes. Conclusion: It seems feasible to map the cortical face processing function and to generate face processing impairment via rTMS. The observed localizations are well in accordance with the contemporary literature, and the mapping did not interfere with rTMS-induced language impairment. The clinical usefulness of preoperative mapping has to be evaluated subsequently.

OBJECTIVE Resection of brain tumors in language-eloquent areas entails the risk of postoperative aphasia. It has been demonstrated via navigated transcranial magnetic stimulation (nTMS) that language function can partially shift to the unaffected hemisphere due to tumor-induced plasticity. Therefore, this study was designed to evaluate whether interhemispheric connectivity (IC) detected by nTMS-based diffusion tensor imaging-fiber tracking (DTI-FT) can be used to predict surgery-related aphasia in patients with brain tumors. METHODS Thirty-eight patients with left-sided perisylvian brain lesions underwent cortical language mapping of both hemispheres by nTMS prior to awake surgery. Then, nTMS-based DTI-FT was conducted with a fractional anisotropy (FA) of 0.01 and 0.2 to visualize nTMS-based IC. Receiver operating characteristics were calculated for the prediction of a postoperative (irrespective of the preoperative state) and a new surgery-related aphasia by the presence of detectable IC. RESULTS Language mapping by nTMS was possible in all patients. Seventeen patients (44.7%) suffered from surgery-related worsening of language performance (transient aphasia according to 3-month follow-up in 16 subjects [42.1%]; new permanent aphasia according to 3-month follow-up in 1 patient [2.6%]). Regarding the correlation of aphasia to nTMS-based IC, statistically significant differences were revealed for both evaluated FA values. However, better results were observed for tractography with an FA of 0.2, which led to a specificity of 93% (postoperative aphasia) and 90% (surgery-related aphasia). For postoperative aphasia, the corresponding OR was 0.1282 (95% CI 0.0143-1.1520), and for surgery-related aphasia the OR was 0.1184 (95% CI 0.0208-0.6754). CONCLUSIONS According to these results, IC detected by preoperative nTMS-based DTI-FT might be regarded as a risk factor for surgery-related aphasia, with a specificity of up to 93%. However, because the majority of enrolled patients suffered from transient aphasia postoperatively, it has to be evaluated whether this approach distinctly leads to similar results among patients with permanent language deficits. Despite this restriction, this approach might contribute to individualized patient consultation prior to tumor resection in clinical practice.

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.

Background: For the navigation of transcranial magnetic stimulation (TMS), various techniques are available. Yet, there are two basic principles underlying them all: electric-field-navigated transcranial magnetic stimulation (En-TMS) and line-navigated transcranial magnetic stimulation (Ln-TMS). The current study was designed to compare both methods., Methods: To explore whether there is a difference in clinical applicability, workflow, and mapping results of both techniques, we systematically compared motor mapping via En-TMS and Ln-TMS in 12 patients suffering from brain tumors., Results: The number of motor-positive stimulation spots and the ratio of positive spots per overall stimulation numbers were significantly higher for En-TMS (motor-positive spots: En-TMS vs. Ln-TMS: 128.3 ± 35.0 vs. 41.3 ± 26.8, p < 0.0001; ratio of motor-positive spots per number of stimulations: En-TMS vs. Ln-TMS: 38.0 ± 9.2 % vs. 20.0 ± 14.4 %, p = 0.0031). Distances between the En-TMS and Ln-TMS motor hotspots were 8.3 ± 4.4 mm on the ipsilesional and 8.6 ± 4.5 mm on the contralesional hemisphere (p = 0.9124)., Conclusions: The present study compares En-TMS and Ln-TMS motor mapping in the neurosurgical context for the first time. Although both TMS systems tested in the present study are explicitly designed for application during motor mapping in patients with brain lesions, there are differences in applicability, workflow, and results between En-TMS and Ln-TMS, which should be distinctly considered during clinical use of the technique. However, to draw final conclusions about accuracy, confirmation of motor-positive Ln-TMS spots by intraoperative stimulation is crucial within the scope of upcoming investigations.

Background: The resection of left-sided perisylvian brain lesions harbours the risk of postoperative language impairment. Therefore the individual patient's language distribution is investigated by intraoperative direct cortical stimulation (DCS) during awake surgery. Yet, not all patients qualify for awake surgery. Non-invasive language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) has frequently shown a high correlation in comparison with the results of DCS language mapping in terms of language-negative brain regions. The present study analyses the extent of resection (EOR) and functional outcome of patients who underwent left-sided perisylvian resection of brain lesions based purely on rTMS language mapping., Methods: Four patients with left-sided perisylvian brain lesions (two gliomas WHO III, one glioblastoma, one cavernous angioma) underwent rTMS language mapping prior to surgery. Data from rTMS language mapping and rTMS-based diffusion tensor imaging fibre tracking (DTI-FT) were transferred to the intraoperative neuronavigation system. Preoperatively, 5 days after surgery (POD5), and 3 months after surgery (POM3) clinical follow-up examinations were performed., Results: No patient suffered from a new surgery-related aphasia at POM3. Three patients underwent complete resection immediately, while one patient required a second rTMS-based resection some days later to achieve the final, complete resection., Conclusions: The present study shows for the first time the feasibility of successfully resecting language-eloquent brain lesions based purely on the results of negative language maps provided by rTMS language mapping and rTMS-based DTI-FT. In very select cases, this technique can provide a rescue strategy with an optimal functional outcome and EOR when awake surgery is not feasible.

Concerning calculation function, studies have already reported on localizing computational function in patients and volunteers by functional magnetic resonance imaging and transcranial magnetic stimulation. However, the development of accurate repetitive navigated TMS (rTMS) with a considerably higher spatial resolution opens a new field in cognitive neuroscience. This study was therefore designed to evaluate the feasibility of rTMS for locating cortical calculation function in healthy volunteers, and to establish this technique for future scientific applications as well as preoperative mapping in brain tumor patients. Twenty healthy subjects underwent rTMS calculation mapping using 5 Hz/10 pulses. Fifty-two previously determined cortical spots of the whole hemispheres were stimulated on both sides. The subjects were instructed to perform the calculation task composed of 80 simple arithmetic operations while rTMS pulses were applied. The highest error rate (80 %) for all errors of all subjects was observed in the right ventral precentral gyrus. Concerning division task, a 45 % error rate was achieved in the left middle frontal gyrus. The subtraction task showed its highest error rate (40 %) in the right angular gyrus (anG). In the addition task a 35 % error rate was observed in the left anterior superior temporal gyrus. Lastly, the multiplication task induced a maximum error rate of 30 % in the left anG. rTMS seems feasible as a way to locate cortical calculation function. Besides language function, the cortical localizations are well in accordance with the current literature for other modalities or lesion studies.

Background: The spatial resolution of repetitive navigated transcranial magnetic stimulation (rTMS) for language mapping is largely unknown. Thus, to determine a minimum spatial resolution of rTMS for language mapping, we evaluated the mapping sessions derived from 19 healthy volunteers for cortical hotspots of no-response errors. Then, the distances between hotspots (stimulation points with a high error rate) and adjacent mapping points (stimulation points with low error rates) were evaluated., Results: Mean distance values of 13.8 ± 6.4 mm (from hotspots to ventral points, range 0.7-30.7 mm), 10.8 ± 4.8 mm (from hotspots to dorsal points, range 2.0-26.5 mm), 16.6 ± 4.8 mm (from hotspots to apical points, range 0.9-27.5 mm), and 13.8 ± 4.3 mm (from hotspots to caudal points, range 2.0-24.2 mm) were measured., Conclusions: According to the results, the minimum spatial resolution of rTMS should principally allow for the identification of a particular gyrus, and according to the literature, it is in good accordance with the spatial resolution of direct cortical stimulation (DCS). Since measurement was performed between hotspots and adjacent mapping points and not on a finer-grained basis, we only refer to a minimum spatial resolution. Furthermore, refinement of our results within the scope of a prospective study combining rTMS and DCS for resolution measurement during language mapping should be the next step.

Object: The resection of left-sided perisylvian brain lesions harbors the risk of postoperative aphasia. Because it is known that language function can shift between hemispheres in brain tumor patients, the preoperative knowledge of the patient's language dominance could be helpful. We therefore investigated the hemispheric language dominance by repetitive navigated transcranial magnetic stimulation (rTMS) and surgery-related deficits of language function., Methods: We pooled the bicentric language mapping data of 80 patients undergoing the resection of left-sided perisylvian brain lesions in our two university neurosurgical departments. We calculated error rates (ERs; ER = errors per stimulations) for both hemispheres and defined the hemispheric dominance ratio (HDR) as the quotient of the left- and right-sided ER (HDR >1= left dominant; HDR <1= right dominant). The course of the patient's language function was evaluated and correlated with the preoperative HDR., Results: Only three of 80 patients (4%) presented with permanent surgery-related aphasia and 24 patients (30%) with transient surgery-related aphasia. The mean HDR (± standard deviation) of patients with new aphasia after five days was significantly higher (1.68±1.07) than the HDR of patients with no new language deficit (1.37±1.08) (p=0.0482). With a predefined cut-off value of 0.5 for HDR, we achieved a sensitivity for predicting new aphasia of 100%., Conclusion: A higher preoperative HDR significantly correlates with an increased risk for transient aphasia. Moreover, the intensive preoperative workup in this study led to a considerably low rate of permanent aphasia., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Repetitive navigated transcranial magnetic stimulation (rTMS) can be used for preoperative language mapping, but it still suffers from comparatively high sensitivity and low specificity when compared to direct cortical stimulation (DCS). Therefore, this study evaluates whether the additional consideration of rTMS-based diffusion tensor imaging fiber tracking (DTI FT) for identifying language-positive brain regions improves specificity when compared to DCS., Methods: We performed rTMS, rTMS-based DTI FT, and DCS during awake surgery combined with object naming in 20 patients suffering from left-sided perisylvian brain lesions. For rTMS, different error rate thresholds (ERTs) and error types were considered, and DTI FT was conducted with individualized fractional anisotropy thresholds (FATs). Then, receiver operating characteristics (ROC) for rTMS vs. DCS, rTMS-based DTI FT vs. DCS, and rTMS spots confirmed by rTMS-based DTI FT vs. DCS were calculated., Results: In general, rTMS vs. DCS was in good accordance with previous literature (sensitivity/specificity: 92.7/13.3 % for all naming errors without ERT). In addition, rTMS-based DTI FT vs. DCS led to balanced results when tracking was based on all errors as well (sensitivity/specificity: 62.8/64.3 % for 100 % FAT). However, rTMS combined with rTMS-based DTI FT vs. DCS did not lead to any improvement in specificity when compared to rTMS vs. DCS alone., Conclusion: The additional use of rTMS-based DTI FT to rTMS did not improve the identification of DCS-positive language areas during awake surgery. Yet, concerning rTMS-based DTI FT, this new technique must be validated itself by intraoperative subcortical stimulation.

Background: Navigated transcranial magnetic stimulation (nTMS) provides language maps in brain tumor patients. Yet, corresponding data on the visualization of language-related subcortical pathways is lacking. Therefore, this study evaluates the feasibility of nTMS-based diffusion tensor imaging fiber tracking (DTI FT) for subcortical language pathways by a fractional anisotropy (FA) protocol., New Method: DTI FT was performed in 37 patients suffering from left-sided perisylvian brain lesions based on nTMS data exclusively, using the FA-based protocol originally established for the corticospinal tract (CST) by Frey et al. (2012): minimum fiber length was 110mm and the highest individual FA value leading to visualization of white matter tracts was determined as the FA threshold (FAT). Then, deterministic DTI FT using an FA value of 100%, 75%, 50%, and 25% of the individual FAT (with 25% as an additional setting to the original protocol) was performed., Results: Our approach visualized 9 language-related subcortical white matter pathways. By using 100% FAT, the mean percentage of visualized tracts was 13.5%, whereas DTI FT performed with 75%, 50%, and 25% FAT detected 30.6%, 61.3%, and 93.7% of language-related fiber tracts, respectively., Comparison With Existing Methods: nTMS language mapping alone is not able to visualize subcortical language-related pathways., Conclusions: This study shows that nTMS language maps are feasible for DTI FT of language-related pathways within the scope of a FAT-based protocol. Although this approach is novel and might be helpful during scientific neuroimaging and tumor resection, intraoperative validation is needed to go beyond the level of feasibility., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Functional magnetic resonance imaging (fMRI) is considered to be the standard method regarding non-invasive language mapping. However, repetitive navigated transcranial magnetic stimulation (rTMS) gains increasing importance with respect to that purpose. However, comparisons between both methods are sparse., Methods: We performed fMRI and rTMS language mapping of the left hemisphere in 40 healthy, right-handed subjects in combination with the tasks that are most commonly used in the neurosurgical context (fMRI: word-generation = WGEN task; rTMS: object-naming = ON task). Different rTMS error rate thresholds (ERTs) were calculated, and Cohen's kappa coefficient and the cortical parcellation system (CPS) were used for systematic comparison of the two techniques., Results: Overall, mean kappa coefficients were low, revealing no distinct agreement. We found the highest agreement for both techniques when using the 2-out-of-3 rule (CPS region defined as language positive in terms of rTMS if at least 2 out of 3 stimulations led to a naming error). However, kappa for this threshold was only 0.24 (kappa of <0, 0.01-0.20, 0.21-0.40, 0.41-0.60, 0.61-0.80 and 0.81-0.99 indicate less than chance, slight, fair, moderate, substantial and almost perfect agreement, respectively)., Conclusions: Because of the inherent differences in the underlying physiology of fMRI and rTMS, the different tasks used and the impossibility of verifying the results via direct cortical stimulation (DCS) in the population of healthy volunteers, one must exercise caution in drawing conclusions about the relative usefulness of each technique for language mapping. Nevertheless, this study yields valuable insights into these two mapping techniques for the most common language tasks currently used in neurosurgical practice.

Objective: The present study aims to investigate the relationship between transcallosal interhemispheric connectivity (IC) and hemispheric language lateralization by using a novel approach including repetitive navigated transcranial magnetic stimulation (rTMS), hemispheric dominance ratio (HDR) calculation, and rTMS-based diffusion tensor imaging fiber tracking (DTI FT)., Methods: 31 patients with left-sided perisylvian brain lesions underwent diffusion tensor imaging (DTI) and rTMS language mapping. Cortical language-positive rTMS spots were used to calculate HDRs (HDR: quotient of the left-sided divided by right-sided naming error rates for corresponding left- and right-sided cortical regions) and to create regions of interest (ROIs) for DTI FT. Then, fibers connecting the rTMS-based ROIs of both hemispheres were tracked, and the correlation of IC to HDRs was calculated via Spearman's rank correlation coefficient (rs)., Results: Fibers connecting rTMS-based ROIs of both hemispheres were detected in 12 patients (38.7%). Within the patients in which IC was detected, the mean number of subcortical IC fibers ± standard deviation (SD) was 138.0 ± 346.5 (median: 7.5; range: 1-1,217 fibers). Regarding rs for the correlation of HDRs and fiber numbers of patients that showed IC, only moderate correlation was revealed., Conclusion: Our approach might be beneficial and technically feasible for further investigation of the relationship between IC and language lateralization. However, only moderate correlation was revealed in the present study., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The authors report a case of soft palate perforation during endemic syphilis. The diagnosis of endemic syphilis was based on the absence of factor in favor of venereal syphilis, highly positive results suggesting VDRL/TPHA association, histology of velar perforation banks and the satisfactory response with closure of the perforation velar after 4 weeks of treatment with Benzathine benzylpenicillin., (Le comitée de rédaction se réserve le droit de revoyer aux auteurs avant toute soumission à l'avis des lecteurs les manuscrits qui ne seraient pas conformes à ces modalités de présentation. En outre il leur conseille de sonserver un examplaire du manuscrit, des figures et des tableaux.)

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.

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.

Objectives: Recent repetitive TMS (rTMS) mapping protocols for language mapping revealed deficits of this method, mainly in posterior brain regions. Therefore this study analyzed the impact of different language tasks on the localization of language-positive brain regions and compared their effectiveness, especially with regard to posterior brain regions., Methods: Nineteen healthy, right-handed subjects performed object naming, pseudoword reading, verb generation, and action naming during rTMS language mapping of the left hemisphere. Synchronically, 5 Hz/10 pulses were applied with a 0 ms delay., Results: The object naming task evoked the highest error rate (14%), followed by verb generation (13%) and action naming (11%). The latter revealed more errors in posterior than in anterior areas. Pseudoword reading barely generated errors, except for phonological paraphasias., Conclusions: In general, among the evaluated language tasks, object naming is the most discriminative task to detect language-positive regions via rTMS. However, other tasks might be used for more specific questions.

Background: Language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) is used for resection planning in patients suffering from brain lesions within regions known to be involved in language function. Yet we also need data that show whether patients benefit clinically from preoperative rTMS for language mapping., Methods: We enrolled 25 patients with language eloquently located brain lesions undergoing preoperative rTMS language mapping (GROUP 1, 2011-2013), with the mapping results not being available for the surgeon, and we matched these patients with 25 subjects who also underwent preoperative rTMS (GROUP 2, 2013-2014), but the mapping results were taken into account during tumor resection. Additionally, cortical language maps were generated by analyzing preoperative rTMS and intraoperative direct cortical stimulation (DCS) data., Results: Mean anterior-posterior (ap) craniotomy extents and overall craniotomy sizes were significantly smaller for the patients in GROUP 2 (Ap: p = 0.0117; overall size: p = 0.0373), and postoperative language deficits were found significantly more frequently for the patients in GROUP 1 (p = 0.0153), although the preoperative language status did not differ between groups (p = 0.7576). Additionally, there was a trend towards fewer unexpected tumor residuals, shorter surgery duration, less peri- or postoperative complications, shorter inpatient stay, and higher postoperative Karnofsky performance status scale (KPS) for the patients in GROUP 2., Conclusions: The present study provides a first hint that the clinical course of patients suffering from brain tumors might be improved by preoperative rTMS language mapping. However, a significant difference between both groups was only found for craniotomy extents and postoperative deficits, but not for other clinical parameters, which only showed a trend toward better results in GROUP 2. Therefore, multicenter trials with higher sample sizes are needed to further investigate the distinct impact of rTMS language mapping on the clinical course of brain tumor patients.

Background: Repetitive 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., Methods: Five 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., Results: An 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., Conclusions: Coil 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.

Background: Knowledge about the cortical representation of semantic processing is mainly derived from functional magnetic resonance imaging (fMRI) or direct cortical stimulation (DCS) studies. Because DCS is regarded as the gold standard in terms of language mapping but can only be used during awake surgery due to its invasive character, repetitive navigated transcranial magnetic stimulation (rTMS)—a non-invasive modality that uses a similar technique as DCS—seems highly feasible for use in the investigation of semantic processing in the healthy human brain., Methods: A total number of 100 (50 left-hemispheric and 50 right-hemispheric) rTMS-based language mappings were performed in 50 purely right-handed, healthy volunteers during an object-naming task. All rTMS-induced semantic naming errors were then counted and evaluated systematically. Furthermore, since the distribution of stimulations within both hemispheres varied between individuals and cortical regions stimulated, all elicited errors were standardized and subsequently related to their cortical sites by projecting the mapping results into the cortical parcellation system (CPS)., Results: Overall, the most left-hemispheric semantic errors were observed after targeting the rTMS to the posterior middle frontal gyrus (pMFG; standardized error rate: 7.3‰), anterior supramarginal gyrus (aSMG; 5.6‰), and ventral postcentral gyrus (vPoG; 5.0‰). In contrast to that, the highest right-hemispheric error rates occurred after stimulation of the posterior superior temporal gyrus (pSTG; 12.4‰), middle superior temporal gyrus (mSTG; 6.2‰), and anterior supramarginal gyrus (aSMG; 6.2‰)., Conclusions: Although error rates were low, the rTMS-based approach of investigating semantic processing during object naming shows convincing results compared to the current literature. Therefore, rTMS seems a valuable, safe, and reliable tool for the investigation of semantic processing within the healthy human brain., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Although language mapping by repetitive navigated transcranial magnetic stimulation (rTMS) gains importance in neuropsychological research and clinical utility, neuroscientists still use different mapping protocols including different stimulation frequencies. To refine the existing language protocol, we tested two different repetition rates of 5 Hz/10 pulses and 7 Hz/10 pulses with a 0 ms delay in 19 healthy subjects. We furthermore investigated differences between both frequencies in case of performance of four different language tasks: object naming, pseudoword reading, verb generation, and action naming., Results: Even the small variance in frequencies revealed statistically significant differences concerning the number and type of language errors. Stimulation with 5 Hz evoked a higher number of all occurred language errors in all language tasks (error rate object naming 14% (5 Hz) vs. 12% (7 Hz); pseudoword reading 4% (5 Hz) vs. 3% (7 Hz); verb generation 13% (5 Hz) vs. 11% (7 Hz); action naming 11% (5 Hz) vs. 9% (7 Hz)), whereas 7 Hz evoked specifically more total speech arrests., Conclusion: These findings suggest that the stimulation frequency has to be adapted to the aim of the rTMS language investigation.

Objectives: The Ear infections Attitudes Research study investigated parental attitudes and awareness towards acute otitis media (AOM) and evaluated the burden of AOM for affected children, their families, and parental work capabilities., Methods: This study, conducted via online interviews in October-November 2010, included parents (N=2867) from 12 countries, whose children aged ≤3.5 years had experienced ≥1 professionally diagnosed AOM episode in the last 6 months (AOM-experienced group; N=1438) or had never experienced any professionally diagnosed AOM episode (non AOM-experienced group; N=1429). The interviews consisted of questions with multiple-choice, five-point scaled or free-text answers. Answers to multiple-choice questions were presented as frequencies of particular responses and those to scaled questions as mean values or percentages of parents considering each aspect as applicable., Results: Parents considered that the main AOM burdens for affected children were pain (mean values on five-point scales: 4.4 and 4.5), disturbed sleep (4.3 and 4.3) and irritability (4.2 and 4.0) and for their families, sleepless nights (4.2 and 3.8) and worries about the child's recovery (4.1 and 4.3) and about potential long-term implications (4.0 and 4.3) in the AOM-experienced and non AOM-experienced groups, respectively. During their child's most recent AOM episode, 95% of parents in the AOM-experienced group used antibiotics, 76% reported that their doctors prescribed antibiotics for immediate use, 13% were advised to return for antibiotic prescription if symptoms did not abate and 9% received a prescription for antibiotics to use if symptoms did not improve. Both reported prescription and usage rates for antibiotics were higher than expected. When their child had AOM, 73% of parents had to be absent from work or rearrange their working hours. Among those who took leave from work, 67% stayed at home for 2-7 days., Conclusions: Parents perceive AOM to be a burden for their child and families, particularly the pain and disturbed sleep due to AOM, and this disease had a significant effect on parents' ability to attend work. Given how common AOM is, this loss of workdays may lead to substantial financial burden for families and the society. Antibiotics were almost invariably used in all countries despite current guidelines., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Background: Repetitive navigated transcranial magnetic stimulation (rTMS) was recently described for mapping of human language areas. However, its capability of detecting language plasticity in brain tumor patients was not proven up to now. Thus, this study was designed to evaluate such data in order to compare rTMS language mapping to language mapping during repeated awake surgery during follow-up in patients suffering from language-eloquent gliomas., Methods: Three right-handed patients with left-sided gliomas (2 opercular glioblastomas, 1 astrocytoma WHO grade III of the angular gyrus) underwent preoperative language mapping by rTMS as well as intraoperative language mapping provided via direct cortical stimulation (DCS) for initial as well as for repeated Resection 7, 10, and 15 months later., Results: Overall, preoperative rTMS was able to elicit clear language errors in all mappings. A good correlation between initial rTMS and DCS results was observed. As a consequence of brain plasticity, initial DCS and rTMS findings only corresponded with the results obtained during the second examination in one out of three patients thus suggesting changes of language organization in two of our three patients., Conclusions: This report points out the usefulness but also the limitations of preoperative rTMS language mapping to detect plastic changes in language function or for long-term follow-up prior to DCS even in recurrent gliomas. However, DCS still has to be regarded as gold standard.

Objectives: Language function is mainly located within the left hemisphere of the brain, especially in right-handed subjects. However, functional MRI (fMRI) has demonstrated changes of language organization in patients with left-sided perisylvian lesions to the right hemisphere. Because intracerebral lesions can impair fMRI, this study was designed to investigate human language plasticity with a virtual lesion model using repetitive navigated transcranial magnetic stimulation (rTMS)., Experimental Design: Fifteen patients with lesions of left-sided language-eloquent brain areas and 50 healthy and purely right-handed participants underwent bilateral rTMS language mapping via an object-naming task. All patients were proven to have left-sided language function during awake surgery. The rTMS-induced language errors were categorized into 6 different error types. The error ratio (induced errors/number of stimulations) was determined for each brain region on both hemispheres. A hemispheric dominance ratio was then defined for each region as the quotient of the error ratio (left/right) of the corresponding area of both hemispheres (ratio >1 = left dominant; ratio <1 = right dominant)., Results: Patients with language-eloquent lesions showed a statistically significantly lower ratio than healthy participants concerning "all errors" and "all errors without hesitations", which indicates a higher participation of the right hemisphere in language function. Yet, there was no cortical region with pronounced difference in language dominance compared to the whole hemisphere., Conclusions: This is the first study that shows by means of an anatomically accurate virtual lesion model that a shift of language function to the non-dominant hemisphere can occur.

To better understand the detection and management of iron overload in transfusion-dependent patients with myelodysplastic syndromes (MDS), a 15-min web- or paper-based survey was conducted among 338 European physicians from 27 countries. Respondents had a mean of 18 years of clinical experience. Forty-six percent and 27% of physicians noted that detecting and treating iron overload were either "very important" or "important," respectively. The main reason for not actively exploring iron overload was related to poor patient prognosis, while the main reasons for not initiating iron chelation therapy were poor patient prognosis and older patient age. Thirty-seven percent and 31% of physicians believed that treating iron overload in these patients was "very important" or "important," respectively. Ninety percent of physicians prescribed iron chelation therapy, and 38% of transfusion-dependent patients received iron chelation therapy. The key reasons for not initiating iron chelation therapy were related to poor patient prognosis (72%), patient age ≥85 years (50%), and comorbidities (34%). The views of these experienced MDS physicians reflect available international MDS treatment guidelines.