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Accurate preoperative mapping is crucial for maximizing tumor removal while minimizing damage to critical brain functions during brain tumor surgery. Navigated transcranial magnetic stimulation (nTMS), magnetoencephalography (MEG), and functional magnetic resonance imaging (fMRI) are established methods for assessing motor and language function. Following PRISMA guidelines, this systematic review analyzes the reliability, clinical utility, and accessibility of these techniques. A total of 128 studies (48 nTMS, 56 fMRI, 24 MEG) were identified from various databases. The analysis finds nTMS to be a safe, standardized method with high accuracy compared to direct cortical stimulation for preoperative motor mapping. Combining nTMS with tractography allows for preoperative assessment of short-term and long-term motor deficits, which may not be possible with fMRI. fMRI data interpretation requires careful consideration of co-activated, non-essential areas (potentially leading to false positives) and situations where neural activity and blood flow are uncoupled (potentially leading to false negatives). These limitations restrict fMRI’s role in preoperative planning for both motor and language functions. While MEG offers high accuracy in motor mapping, its high cost and technical complexity contribute to the limited number of available studies. Studies comparing preoperative language mapping techniques with direct cortical stimulation show significant variability across all methods, highlighting the need for larger, multicenter studies for validation. Repetitive nTMS speech mapping offers valuable negative predictive value, allowing clinicians to evaluate whether a patient should undergo awake or asleep surgery. Language function monitoring heavily relies on the specific expertise and experience available at each center, making it challenging to establish general recommendations.

ABSTRACT: Background: Spine surgical training faces increasing challenges due to restricted working hours and greater sub specialization. Modern simulators offer a promising approach to teaching both simple and complex spinal procedures. This study evaluated the acceptance and efficacy of spine simulator training using a lumbar herniated disc model tested by 16 neurosurgical residents (PGY-1-6), and compared 3D and 2D teaching methods. Methods: Sixteen residents utilized the Realists RealSpine L4/L5 disc simulator with both microscope and exoscope. A mixed-methods analysis assessed the efficacy and acceptance of the training. Six PGY-1 residents participated in a learning curve study, divided into exoscopic and microscopic cohorts. Each group watched a tutorial in either 3D or 2D, followed by 3 surgical sessions. Endpoints included surgical progress within 30 minutes and complication rates. Microsurgical skills and mental concepts were evaluated on a numeric Likert Scale. Results: Participants rated the simulator training favorably, with a median score of 8/10 across 6 categories. The learning curve study showed a 30% improvement in microsurgical performance. The completion rate of herniated disc removal increased from 50% at T2 to 100% at T3 and T4. Significant improvement in mental concept was observed (p=.035), with slightly better consolidation in the exoscope group. Self-assessments revealed significantly improved skills across all participants. Conclusions: Spine simulator training was well-received and resulted in improvements in both mental concept and microsurgical performance, with enhanced outcomes in the 3D teaching/exoscope group. This study supports the integration of spine simulators into spine surgical residency, particularly for early-stage training, to improve both cognitive and practical surgical skills.

BackgroundSubjective reports can reveal relevant information regarding the nature of the impairment of brain tumor patients, unveiling potential gaps in current assessment practices. The co-occurrence of language and memory impairments has been previously reported, albeit scarcely. The aim of this study is therefore to understand the co-occurrence of subjective language and memory complaints in the preoperative state of brain tumor patients and its impact on Quality of Life (QoL).Methods31 brain tumor patients (12 LGG, 19 HGG) underwent a semi-structured interview to assess subjective complaints of language deficits, co-occurrences between language and memory dysfunction, and changes in QoL. Group and subgroup analyses were conducted to provide general and tumor grade specific data.Results48.4% of patients mentioned co-occurrence of language and memory impairments in reading, writing, and conversation. The HGG group reported co-occurrences in all three of these (reading: 31.6%; writing: 21.1%; conversation: 26.3%), while the LGG only described co-occurrences in reading (25%) and conversation (8.3%), although these were not statistically significant. All patients with co-occurring language and memory deficits reported these to be linked to reduced QoL (48.4%). In patients with an HGG, this number was slightly higher (52.6%) than in patients with an LGG (41.7%).ConclusionLanguage impairments co-occur with memory dysfunction as perceived in patients’ daily life. Patients see these impairments as affecting their quality of life. Further attention to dedicated language and memory tasks seems necessary.

Digital twins enable simulation, comprehensive analysis and predictions, as virtual representations of physical systems. They are also finding increasing interest and application in the healthcare sector, with a particular focus on digital twins of the brain. We discuss how digital twins in neuroscience enable the modeling of brain functions and pathology as they offer an in-silico approach to studying the brain and illustrating the complex relationships between brain network dynamics and related functions. To showcase the capabilities of digital twinning in neuroscience we demonstrate how the impact of brain tumors on the brain’s physical structures and functioning can be modeled in relation to the philosophical concept of plasticity. Against this technically derived backdrop, which assumes that the brain’s nonlinear behavior toward improvement and repair can be modeled and predicted based on MRI data, we further explore the philosophical insights of Catherine Malabou. Malabou emphasizes the brain’s dual capacity for adaptive and destructive plasticity. We will discuss in how far Malabou’s ideas provide a more holistic theoretical framework for understanding how digital twins can model the brain’s response to injury and pathology, embracing Malabou’s concept of both adaptive and destructive plasticity which provides a framework to address such yet incomputable aspects of neuroscience and the sometimes seemingly unfavorable dynamics of neuroplasticity helping to bridge the gap between theoretical research and clinical practice.

Abstract Background The extent of resection of glioma is one of the most important predictors of the survival duration of patients after surgery. The presence of eloquent areas within or near a tumor often limits resection, as resection of these areas would result in functional loss and reduced quality of life. The aim of this randomized, triple-blind, sham-controlled study is to investigate the capability of repetitive navigated transcranial magnetic stimulation (rnTMS) over the primary motor cortex to facilitate the functional reorganization of the motor network. Methods One hundred forty-eight patients with tumors in movement-relevant areas will be included in this randomized, sham-controlled, bicentric, triple-blind clinical trial. Patients considered at high risk for postoperative motor deficits according to an initial nTMS assessment will receive inhibitory rnTMS at 1 Hz for 30 min followed by a short motor training of 10 min. Stimulation will be applied to the fiber endings of the corticospinal tract closest to the tumor based on individualized tractography. Stimulation will be performed twice daily for each 30 min for 5–28 days depending on the individually available time between study inclusion and surgery. The intervention is controlled by a sham stimulation group (1:1 randomization), where a plastic adapter will be placed on the coil. We expect a comparable or better motor status 3 months postoperatively as measured by the British Medical Research Council (BMRC) score for the affected upper extremity (non-inferiority) and a higher rate of gross total resections (superiority) in the rnTMS compared to the sham group. Discussion The generated reorganization of the brain’s areas for motor function should allow a more extensive and safer removal of the tumor while preserving neurological and motor function. This would improve both survival and quality of life of our patients. Trial registration DRKS.de DRKS00017232 . Registered on 28 January 2020.

ObjectiveSurgical resection of motor eloquent tumors poses the risk of causing postoperative motor deficits which leads to reduced quality of life in these patients. Currently, rehabilitative procedures are limited with physical therapy being the main treatment option. This study investigated the efficacy of repetitive navigated transcranial magnetic stimulation (rTMS) for treatment of motor deficits after supratentorial tumor resection.MethodsThis randomized, double-blind, sham-controlled trial (DRKS00010043) recruited patients with a postoperatively worsened upper extremity motor function immediately postoperatively. They were randomly assigned to receive rTMS (1Hz, 110% RMT, 15 minutes, 7 days) or sham stimulation to the motor cortex contralateral to the injury followed by physical therapy. Motor and neurological function as well as quality of life were assessed directly after the intervention, one month and three months postoperatively.ResultsThirty patients were recruited for this study. There was no significant difference between both groups in the primary outcome, the Fugl Meyer score three months postoperatively [Group difference (95%-CI): 5.05 (-16.0; 26.1); p=0.631]. Patients in the rTMS group presented with better hand motor function one month postoperatively. Additionally, a subgroup of patients with motor eloquent ischemia showed lower NIHSS scores at all timepoints.ConclusionsLow-frequency rTMS facilitated the recovery process in stimulated hand muscles, but with limited generalization to other functional deficits. Long-term motor deficits were not impacted by rTMS. Given the reduced life expectancy in these patients a shortened recovery duration of deficits can still be of high significance.Clinical Trial Registrationhttps://drks.de/DRKS00010043.

Introduction: Surgery on the brainstem level is associated with a high-risk of postoperative morbidity. Recently, we have introduced the combination of navigated transcranial magnetic stimulation (nTMS) and diffusion tensor imaging (DTI) tractography to define functionally relevant motor fibers tracts on the brainstem level to support operative planning and risk stratification in brainstem cavernomas. Research question: Evaluate this method and assess it's clinical impact for the surgery of brainstem gliomas. Material and methods: Patients with brainstem gliomas were examined preoperatively with motor nTMS and DTI tractography. A fractional anisotropy (FA) value of 75% of the individual FA threshold (FAT) was used to track descending corticospinal (CST) and -bulbar tracts (CBT). The distance between the tumor and the somatotopic tracts (hand, leg, face) was measured and diffusion parameters were correlated to the patients’ outcome. Results: 12 patients were enrolled in this study, of which 6 underwent surgical resection, 5 received a stereotactic biopsy and 1 patient received conservative treatment. In all patients nTMS mapping and somatotopic tractography were performed successfully. Low FA values correlated with clinical symptoms revealing tract alteration by the tumor (p = 0.049). A tumor-tract distance (TTD) above 2 mm was the critical limit to achieve a safe complete tumor resection. Discussion and conclusion: nTMS based DTI tractography combined with local diffusion analysis is a valuable tool for preoperative visualization and functional assessment of relevant motor fiber tracts, improving planning of safe entry corridors and perioperative risk stratification in brainstem gliomas tumors. This technique allows for customized treatment strategy to maximize patients’ safety.

Objective: Patients with left perisylvian gliomas might undergo language mapping with nTMS in preparation for awake brain surgery. Action naming is an important addition to the presurgical language mapping protocol. However, it has not yet been determined whether specific action stimuli can influence mapping outcomes in terms of number and/or localisation of induced errors. Methods: We investigated this question by employing tractography-based nTMS language mapping of the left arcuate fasciculus (AF) with two types of verbs: transitive and intransitive. Data were collected from 22 patients with a left perisylvian glioma. Results: Our results demonstrated that nTMS induced a higher error rate with transitive rather than intransitive verbs, specifically during stimulation of the posterior temporal terminations of the left AF (transitive error rate: 8.3%; intransitive error rate: 4.8%). The effect was absent when gliomas displaced the temporal terminations of the AF. Also, nTMS triggered a higher number of semantic errors with transitive (vs intransitive) actions during stimulation of the posterior temporal terminations of the AF (semantic error rate – transitives: 3.3%; semantic error rate – intransitives: 0%). Conclusion: Our work highlights that clinical outcomes of language mapping with nTMS are affected by the choice of linguistic stimuli. Transitive verbs may be suited to achieve optimal nTMS mapping outcomes in posterior temporal areas of the left AF in this population. Displacement of white matter terminations due to the tumor can affect these results, and semantic errors may indicate core language processes that can be mapped when administering transitive verbs.

Abstract Three-dimensional exoscopes have been designed to overcome certain insufficiencies of operative microscopes. We aimed to explore the clinical use in various spinal surgeries. We performed surgery on patients with different spine entities in a neurosurgical department according to the current standard operating procedures over a 4-week period of time. The microsurgical part has been performed with Aesculap AEOS 3D microscope. Three neurosurgeons with different degree of surgical expertise completed a questionnaire with 43 items based on intraoperative handling and feasibility after the procedures. We collected and analyzed data from seventeen patients (35% male/65% female) with a median age of 70 years [CI 47–86] and median BMI of 25.8 kg/m2 [range 21–33]. We included a variety of spinal pathologies (10 degenerative, 4 tumor and 3 infectious cases) with different level of complexity. Regarding setup conflicts we observed issues with adjustment of the monitor position or while using additional equipment (e.g. fluoroscopy in fusion surgery) (p = 0.007/p = 0.001). However image resolution and sharpness as well as 3D-depth perception were completely satisfactory for all surgeons in all procedures. The utilization of the exoscopic arm was easy for 76.5% of the surgeons, and all of them declared a significant improvement of the surgical corridor. The 3D-exoscope implementation appears to achieve very satisfactory results in spinal procedures especially with minimally invasive approaches.

BackgroundThe supplementary motor area (SMA) is important for motor and language function. Damage to the SMA may harm these functions, yet tools for a preoperative assessment of the area are still sparse.ObjectiveThe aim of this study was to validate a mapping protocol using repetitive navigated transcranial magnetic stimulation (rnTMS) and extend this protocol for both hemispheres and lower extremities.MethodsTo this purpose, the SMA of both hemispheres were mapped based on a finger tapping task for 30 healthy subjects (35.97 ± 15.11, range 21–67 years; 14 females) using rnTMS at 20 Hz (120% resting motor threshold (RMT)) while controlling for primary motor cortex activation. Points with induced errors were marked on the corresponding MRI. Next, on the identified SMA hotspot a bimanual finger tapping task and the Nine-Hole Peg Test (NHPT) were performed. Further, the lower extremity was mapped at 20 Hz (140%RMT) using a toe tapping task.ResultsMean finger tapping scores decreased significantly during stimulation (25.70taps) compared to baseline (30.48; p

BackgroundDamage to the supplementary motor area (SMA) can lead to impairments of motor and language function. A detailed preoperative mapping of functional boarders of the SMA could therefore aid preoperative diagnostics in these patients.ObjectiveThe aim of this study was the development of a repetitive nTMS protocol for non-invasive functional mapping of the SMA while assuring effects are caused by SMA rather than M1 activation.MethodsThe SMA in the dominant hemisphere of 12 healthy subjects (28.2 ± 7.7 years, 6 females) was mapped using repetitive nTMS at 20 Hz (120% RMT), while subjects performed a finger tapping task. Reductions in finger taps were classified in three error categories (≤15% = no errors, 15–30% = mild, >30% significant). The location and category of induced errors was marked in each subject’s individual MRI. Effects of SMA stimulation were then directly compared to effects of M1 stimulation in four different tasks (finger tapping, writing, line tracing, targeting circles).ResultsMapping of the SMA was possible for all subjects, yet effect sizes varied. Stimulation of the SMA led to a significant reduction of finger taps compared to baseline (BL: 45taps, SMA: 35.5taps; p

Tumors and their location distinctly alter both local and global brain connectivity within the ipsilesional hemisphere of glioma patients.

Background: Two statistical models have been established to evaluate characteristics associated with postoperative motor outcome in patients with glioma associated to the motor cortex (M1) or the corticospinal tract (CST). One model is based on a clinicoradiological prognostic sum score (PrS) while the other one relies on navigated transcranial magnetic stimulation (nTMS) and diffusion-tensor-imaging (DTI) tractography. The objective was to compare the models regarding their prognostic value for postoperative motor outcome and extent of resection (EOR) with the aim of developing a combined, improved model. Methods: We retrospectively analyzed a consecutive prospective cohort of patients who underwent resection for motor associated glioma between 2008 and 2020, and received a preoperative nTMS motor mapping with nTMS-based diffusion tensor imaging tractography. The primary outcomes were the EOR and the motor outcome (on the day of discharge and 3 months postoperatively according to the British Medical Research Council (BMRC) grading). For the nTMS model, the infiltration of M1, tumor-tract distance (TTD), resting motor threshold (RMT) and fractional anisotropy (FA) were assesed. For the PrS score (ranging from 1 to 8, lower scores indicating a higher risk), we assessed tumor margins, volume, presence of cysts, contrast agent enhancement, MRI index (grading white matter infiltration), preoperative seizures or sensorimotor deficits. Results: Two hundred and three patients with a median age of 50 years (range: 20–81 years) were analyzed of whom 145 patients (71.4%) received a GTR. The rate of transient new motor deficits was 24.1% and of permanent new motor deficits 18.8%. The nTMS model demonstrated a good discrimination ability for the short-term motor outcome at day 7 of discharge (AUC = 0.79, 95 %CI: 0.72–0.86) and the long-term motor outcome after 3 months (AUC = 0.79, 95 %CI: 0.71–0.87). The PrS score was not capable to predict the postoperative motor outcome in this cohort but was moderately associated with the EOR (AUC = 0.64; CI 0.55–0.72). An improved, combined model was calculated to predict the EOR more accurately (AUC = 0.74, 95 %CI: 0.65–0.83). Conclusion: The nTMS model was superior to the clinicoradiological PrS model for potentially predicting the motor outcome. A combined, improved model was calculated to estimate the EOR. Thus, patient counseling and surgical planning in patients with motor-associated tumors should be performed using functional nTMS data combined with tractography.

IntroductionThis study explores the feasibility of implementing a tractography-based navigated transcranial magnetic stimulation (nTMS) language mapping protocol targeting cortical terminations of the arcuate fasciculus (AF). We compared the results and distribution of errors from the new protocol to an established perisylvian nTMS protocol that stimulated without any specific targeting over the entire perisylvian cortex.MethodsSixty right-handed patients with language-eloquent brain tumors were examined in this study with one half of the cohort receiving the tractographybased protocol and the other half receiving the perisylvian protocol. Probabilistic tractography using MRtrix3 was performed for patients in the tractography-based group to identify the AF’s cortical endpoints. nTMS mappings were performed and resulting language errors were classified into five psycholinguistic groups.ResultsTractography and nTMS were successfully performed in all patients. The tractogram-based group showed a significantly higher median overall ER than the perisylvian group (3.8% vs. 2.9% p

Background: Navigated repetitive transcranial magnetic stimulation (nrTMS) is effective therapy for stroke patients. Neurorehabilitation could be supported by low-frequency stimulation of the non-damaged hemisphere to reduce transcallosal inhibition. Objective: The present study examines the effect of postoperative nrTMS therapy of the unaffected hemisphere in glioma patients suffering from acute surgery-related paresis of the upper extremity (UE) due to subcortical ischemia. Methods: We performed a randomized, sham-controlled, double-blinded trial on patients suffering from acute surgery-related paresis of the UE after glioma resection. Patients were randomly assigned to receive either low frequency nrTMS (1 Hz, 15 min) or sham stimulation directly before physical therapy for 7 consecutive days. We performed primary and secondary outcome measures on day 1, on day 7, and at a 3-month follow-up (FU). The primary endpoint was the change in Fugl-Meyer Assessment (FMA) at FU compared to day 1 after surgery. Results: Compared to the sham stimulation, nrTMS significantly improved outcomes between day 1 and FU based on the FMA (mean [95% CI] +31.9 [22.6, 41.3] vs. +4.2 [-4.1, 12.5]; P = .001) and the National Institutes of Health Stroke Scale (NIHSS) (−5.6 [-7.5, −3.6] vs. −2.4 [-3.6, −1.2]; P = .02). To achieve a minimal clinically important difference of 10 points on the FMA scale, the number needed to treat is 2.19. Conclusion: The present results show that patients suffering from acute surgery-related paresis of the UE due to subcortical ischemia after glioma resection significantly benefit from low-frequency nrTMS stimulation therapy of the unaffected hemisphere. Clinical trial registration: Local institutional registration: 12/15; ClinicalTrials.gov number: NCT03982329

ObjectRecent studies demonstrated that gross total resection of brain metastases cannot always be achieved. Subtotal resection (STR) can result in an early recurrence and might affect patient survival. We initiated a prospective observational study to establish a MRI-based risk assessment for incomplete resection of brain metastases.MethodsAll patients in whom ≥1 brain metastasis was resected were prospectively included in this study (DRKS ID: DRKS00021224; Nov 2020 – Nov 2021). An interdisciplinary board of neurosurgeons and neuroradiologists evaluated the pre- and postoperative MRI (≤48h after surgery) for residual tumor. Extensive neuroradiological analyses were performed to identify risk factors for an unintended STR which were integrated into a regression tree analysis to determine the patients’ individual risk for a STR.ResultsWe included 150 patients (74 female; mean age: 61 years), in whom 165 brain metastases were resected. A STR was detected in 32 cases (19.4%) (median residual tumor volume: 1.36ml, median EORrel: 93.6%), of which 6 (3.6%) were intended STR (median residual tumor volume: 3.27ml, median EORrel: 67.3%) - mainly due to motor-eloquent location - and 26 (15.8%) were unintended STR (uSTR) (median residual tumor volume: 0.64ml, median EORrel: 94.7%). The following risk factors for an uSTR could be identified: subcortical metastasis ≥5mm distant from cortex, diffuse contrast agent enhancement, proximity to the ventricles, contact to falx/tentorium and non-transcortical approaches. Regression tree analysis revealed that the individual risk for an uSTR was mainly associated to the distance from the cortex (distance ≥5mm vs.

Low-frequency repetitive transcranial magnetic stimulation (rTMS) is capable of inducing changes in the functional organization of underlying brain regions, however, often at the cost of long stimulation protocols over several weeks. As these protocols can be difficult to implement in clinical settings, the aim of the present pilot study was to show the feasibility and safety of an accelerated low-frequency rTMS protocol applying multiple sessions daily. To this purpose, nine healthy subjects received 14 sessions of rTMS (1 Hz, 30 min, 110% RMT) to the hand motor hotspot. Subjects received stimulation for either 14 days once daily [classical rTMS (c-rTMS)], 7 days twice daily (accelerated rTMS; a-rTMS), or sham stimulation for 14 days once daily (s-rTMS). Daily stimulation sessions in the a-rTMS group were delivered with a 90-min break in between. In total, 74% of rTMS sessions in the c-rTMS group, 89% in the a-rTMS group, and 98% in the s-rTMS group were free of any side effects. Brief headaches and fatigue in stimulated muscle groups were the most frequent side effects. All side effects were reported to be at maximum mild and of short duration. Thus, accelerated low-frequency rTMS of the motor cortex seems to be a safe and feasible method, previously shown to induce a functional reorganization of the motor system. By shortening treatment duration in days, this approach can potentially make rTMS protocols more accessible to a wider range of patients.

Abstract Background According to the new WHO classification from 2016, molecular profiles have shown to provide reliable information about prognosis and treatment response. The purpose of our study is to evaluate the diagnostic potential of non-invasive quantitative T2 mapping in the detection of IDH1/2 mutation status in grade II-III gliomas. Methods Retrospective evaluation of MR examinations in 30 patients with histopathological proven WHO-grade II (n = 9) and III (n = 21) astrocytomas (18 IDH-mutated, 12 IDH-wildtype). Consensus annotation by two observers by use of ROI’s in quantitative T2-mapping sequences were performed in all patients. T2 relaxation times were measured pixelwise. Results A significant difference (p = 0,0037) between the central region of IDH-mutated tumors (356,83 ± 114,97 ms) and the IDH-wildtype (199,92 ± 53,13 ms) was found. Furthermore, relaxation times between the central region (322,62 ± 127,41 ms) and the peripheral region (211,1 ± 74,16 ms) of WHO grade II and III astrocytomas differed significantly (p = 0,0021). The central regions relaxation time of WHO-grade II (227,44 ± 80,09 ms) and III gliomas (322,62 ± 127,41 ms) did not differ significantly (p = 0,2276). The difference between the smallest and the largest T2 value (so called “range”) is significantly larger (p = 0,0017) in IDH-mutated tumors (230,89 ± 121,11 ms) than in the IDH-wildtype (96,33 ± 101,46 ms). Interobserver variability showed no significant differences. Conclusions Quantitative evaluation of T2-mapping relaxation times shows significant differences regarding the IDH-status in WHO grade II and III gliomas adding important information regarding the new 2016 World Health Organization (WHO) Classification of tumors of the central nervous system. This to our knowledge is the first study regarding T2 mapping and the IDH1/2 status shows that the mutational status seems to be more important for the appearance on T2 images than the WHO grade.

BackgroundThe resection of a motor-eloquent glioma should be guided by intraoperative neurophysiological monitoring (IOM) but its interpretation is often difficult and may (unnecessarily) lead to subtotal resection. Navigated transcranial magnetic stimulation (nTMS) combined with diffusion-tensor-imaging (DTI) is able to stratify patients with motor-eloquent lesion preoperatively into high- and low-risk cases with respect to a new motor deficit.ObjectiveTo analyze to what extent preoperative nTMS motor risk stratification can improve the interpretation of IOM phenomena.MethodsIn this monocentric observational study, nTMS motor mapping with DTI fiber tracking of the corticospinal tract was performed before IOM-guided surgery for motor-eloquent gliomas in a prospectively collected cohort from January 2017 to October 2020. Descriptive analyses were performed considering nTMS data (motor cortex infiltration, resting motor threshold (RMT), motor evoked potential (MEP) amplitude, latency) and IOM data (transcranial MEP monitoring, intensity of monopolar subcortical stimulation (SCS), somatosensory evoked potentials) to examine the association with the postoperative motor outcome (assessed at day of discharge and at 3 months).ResultsThirty-seven (56.1%) of 66 patients (27 female) with a median age of 48 years had tumors located in the right hemisphere, with glioblastoma being the most common diagnosis with 39 cases (59.1%). Three patients (4.9%) had a new motor deficit that recovered partially within 3 months and 6 patients had a persistent deterioration (9.8%). The more risk factors of the nTMS risk stratification model (motor cortex infiltration, tumor-tract distance (TTD) ≤8mm, RMTratio 110%) were detected, the higher was the risk for developing a new postoperative motor deficit, whereas no patient with a TTD >8mm deteriorated. Irreversible MEP amplitude decrease >50% was associated with worse motor outcome in all patients, while a MEP amplitude decrease ≤50% or lower SCS intensities ≤4mA were particularly correlated with a postoperative worsened motor status in nTMS-stratified high-risk cases. No patient had postoperative deterioration of motor function (except one with partial recovery) when intraoperative MEPs remained stable or showed only reversible alterations.ConclusionsThe preoperative nTMS-based risk assessment can help to interpret ambiguous IOM phenomena (such as irreversible MEP amplitude decrease ≤50%) and adjustment of SCS stimulation intensity.

The physiological mechanisms of corticospinal excitability and factors influencing its measurement with transcranial magnetic stimulation are still poorly understood. A recent study reported an impact of functional connectivity (FC) between the primary motor cortex (M1) and the dorsal premotor cortex (PMd) on the resting motor threshold (RMT) of the dominant hemisphere. We aimed to replicate these findings in a larger sample of 38 healthy right-handed subjects with data from both hemispheres. Resting-state FC was assessed between the M1 and five a priori defined motor-relevant regions on each hemisphere as well as interhemispherically between both primary motor cortices. Following the procedure by the original authors, we included age, cortical gray matter volume, and coil-to-cortex distance (CCD) as further predictors in the analysis. We report replication models for the dominant hemisphere as well as an extension to data from both hemispheres and support the results with Bayes factors. FC between the M1 and the PMd did not explain the variability in the RMT, and we obtained moderate evidence for the absence of this effect. In contrast, CCD could be confirmed as an important predictor with strong evidence. These findings contradict the previously proposed effect, thus questioning the notion of the PMd playing a major role in modifying corticospinal excitability.

Tumors infiltrating the motor system lead to significant disability, often caused by corticospinal tract injury. The delineation of the healthy-pathological white matter (WM) interface area, for which diffusion magnetic resonance imaging (dMRI) has shown promising potential, may improve treatment outcome. However, up to 90% of white matter (WM) voxels include multiple fiber populations, which cannot be correctly described with traditional metrics such as fractional anisotropy (FA) or apparent diffusion coefficient (ADC). Here, we used a novel fixel-based along-tract analysis consisting of constrained spherical deconvolution (CSD)-based probabilistic tractography and fixel-based apparent fiber density (FD), capable of identifying fiber orientation specific microstructural metrics. We addressed this novel methodology’s capability to detect corticospinal tract impairment. We measured and compared tractogram-related FD and traditional microstructural metrics bihemispherically in 65 patients with WHO grade III and IV gliomas infiltrating the motor system. The cortical tractogram seeds were based on motor maps derived by transcranial magnetic stimulation. We extracted 100 equally distributed cross-sections along each streamline of corticospinal tract (CST) for along-tract statistical analysis. Cross-sections were then analyzed to detect differences between healthy and pathological hemispheres. All metrics showed significant differences between healthy and pathologic hemispheres over the entire tract and between peritumoral segments. Peritumoral values were lower for FA and FD, but higher for ADC within the entire cohort. FD was more specific to tumor-induced changes in CST than ADC or FA, whereas ADC and FA showed higher sensitivity. The bihemispheric along-tract analysis provides an approach to detect subject-specific structural changes in healthy and pathological WM. In the current clinical dataset, the more complex FD metrics did not outperform FA and ADC in terms of describing corticospinal tract impairment.

Objectives: Injury to major white matter pathways during language-area associated glioma surgery often leads to permanent loss of neurological function. The aim was to establish standardized tractography of language pathways as a predictor of language outcome in clinical neurosurgery. Methods: We prospectively analyzed 50 surgical cases of patients with left perisylvian, diffuse gliomas. Standardized preoperative Diffusion-Tensor-Imaging (DTI)-based tractography of the 5 main language tracts (Arcuate Fasciculus [AF], Frontal Aslant Tract [FAT], Inferior Fronto-Occipital Fasciculus [IFOF], Inferior Longitudinal Fasciculus [ILF], Uncinate Fasciculus [UF]) and spatial analysis of tumor and tracts was performed. Postoperative imaging and the resulting resection map were analyzed for potential surgical injury of tracts. The language status was assessed preoperatively, postoperatively and after 3 months using the Aachen Aphasia Test and Berlin Aphasia Score. Correlation analyses, two-step cluster analysis and binary logistic regression were used to analyze associations of tractography results with language outcome after surgery. Results: In 14 out of 50 patients (28%), new aphasic symptoms were detected 3 months after surgery. The preoperative infiltration of the AF was associated with functional worsening (cc = 0.314; p = 0.019). Cluster analysis of tract injury profiles revealed two areas particularly related to aphasia: the temporo-parieto-occipital junction (TPO; temporo-parietal AF, middle IFOF, middle ILF) and the temporal stem/peri-insular white matter (middle IFOF, anterior ILF, temporal UF, temporal AF). Injury to these areas (TPO: OR: 23.04; CI: 4.11 – 129.06; temporal stem: OR: 21.96; CI: 2.93 – 164.41) was associated with a higher-risk of persisting aphasia. Conclusions: Tractography of language pathways can help to determine the individual aphasia risk profile pre-surgically. The TPO and temporal stem/peri-insular white matter were confirmed as functional nodes particularly sensitive to surgical injuries.

Repetitive TMS (rTMS) allows for non-invasive and transient disruption of local neuronal functioning. We used machine learning approaches to assess whether brain tumor patients can be accurately classified into aphasic and non-aphasic groups using their rTMS language mapping results as input features. Given that each tumor affects the subject-specific language networks differently, resulting in heterogenous rTMS functional mappings, we propose the use of machine learning strategies to classify potential patterns of rTMS language mapping results. We retrospectively included 90 patients with left perisylvian world health organization (WHO) grade II-IV gliomas that underwent presurgical navigated rTMS language mapping. Within our cohort, 29 of 90 (32.2%) patients suffered from at least mild aphasia as shown in the Aachen Aphasia Test based Berlin Aphasia Score (BAS). After spatial normalization to MNI 152 of all rTMS spots, we calculated the error rate (ER) in each stimulated cortical area (28 regions of interest, ROI) by automated anatomical labeling parcellation (AAL3) and IIT. We used a support vector machine (SVM) to classify significant areas in relation to aphasia. After feeding the ROIs into the SVM model, it revealed that in addition to age (w = 2.98), the ERs of the left supramarginal gyrus (w = 3.64), left inferior parietal gyrus (w = 2.28) and right pars triangularis (w = 1.34) contributed more than other features to the model. The model’s sensitivity was 86.2%, the specificity was 82.0%, the overall accuracy was 85.5% and the AUC was 89.3%. Our results demonstrate an increased vulnerability of right inferior pars triangularis to rTMS in aphasic patients due to left perisylvian gliomas. This finding points towards a functional relevant involvement of the right pars triangularis in response to aphasia. The tumor location feature, specified by calculating overlaps with white and grey matter atlases, did not affect the SVM model. The left supramarginal gyrus as a feature improved our SVM model the most. Additionally, our results could point towards a decreasing potential for neuroplasticity with age.

Background: Surgical planning with nTMS-based tractography is proven to increase safety during surgery. A preoperative risk stratification model has been published based on the M1 infiltration, RMT ratio, and tumor to corticospinal tract distance (TTD). The correlation of TTD with corticospinal tract to resection cavity distance (TRD) and outcome is needed to further evaluate the validity of the model. Aim of the study: To use the postop MRI-derived resection cavity to measure how closely the resection cavity approximated the preoperatively calculated corticospinal tract (CST) and how this correlates with the risk model and the outcome. Methods: We included 183 patients who underwent nTMS-based DTI and surgical resection for presumed motor-eloquent gliomas. TTD, TRD, and motor outcome were recorded and tested for correlations. The intraoperative monitoring documentation was available for a subgroup of 48 patients, whose responses were correlated to TTD and TRD. Results: As expected, TTD and TRD showed a good correlation (Spearman’s ρ = 0.67, p < 0.001). Both the TTD and the TRD correlated significantly with the motor outcome at three months (Kendall’s Tau-b 0.24 for TTD, 0.31 for TRD, p < 0.001). Interestingly, the TTD and TRD correlated only slightly with residual tumor volume, and only after correction for outliers related to termination of resection due to intraoperative monitoring events or the proximity of other eloquent structures (TTD ρ = 0.32, p < 0.001; TRD ρ = 0.19, p = 0.01). This reflects the fact that intraoperative monitoring (IOM) phenomena do not always correlate with preoperative structural analysis, and that additional factors influence the intraoperative decision to abort resection, such as the adjacency of other vulnerable structures. The TTD was also significantly correlated with variations in motor evoked potential (MEP) responses (no/reversible decrease vs. irreversible decrease; p = 0.03). Conclusions: The TTD approximates the TRD well, confirming the best predictive parameter and giving strength to the nTMS-based risk stratification model. Our analysis of TRD supports the use of the nTMS-based TTD measurement to estimate the resection preoperatively, also confirming the 8 mm cutoff. Nevertheless, the TRD proved to have a slightly stronger correlation with the outcome as the surgeon’s experience, anatomofunctional knowledge, and MEP observations influence the expected EOR.

Object: Navigated transcranial magnetic stimulation (nTMS) combined with diffusion tensor imaging (DTI) is used preoperatively in patients with eloquent-located brain lesions and allows analyzing non-invasively the spatial relationship between the tumor and functional areas (e.g. the motor cortex and the corticospinal tract [CST]). In this study, we examined the diffusion parameters FA (fractional anisotropy) and ADC (apparent diffusion coefficient) within the CST in different locations and analyzed their interrater reliability and usefulness for predicting the patients' motor outcome with a precise approach of specific region of interest (ROI) seeding based on the color-coded FA-map. Methods: Prospectively collected data of 30 patients undergoing bihemispheric nTMS mapping followed by nTMS-based DTI fiber tracking prior to surgery of motor eloquent high-grade gliomas were analyzed by 2 experienced and 1 unexperienced examiner. The following data were scrutinized for both hemispheres after tractography based on nTMS-motor positive cortical seeds and a 2nd region of interest in one layer of the caudal pons defined by the color-coded FA-map: the pre- and postoperative motor status (day of discharge und 3months), the closest distance between the tracts and the tumor (TTD), the fractional anisotropy (FA) and the apparent diffusion coefficient (ADC). The latter as an average within the CST as well as specific values in different locations (peritumoral, mesencephal, pontine). Results: Lower average FA-values within the affected CST as well as higher average ADC-values are significantly associated with deteriorated postoperative motor function (p=0.006 and p=0.026 respectively). Segmental analysis within the CST revealed that the diffusion parameters are especially disturbed on a peritumoral level and that the degree of their impairment correlates with motor deficits (FA p=0.065, ADC p=0.007). No significant segmental variation was seen in the healthy hemisphere. The interrater reliability showed perfect agreement for almost all analyzed parameters. Conclusions: Adding diffusion weighted imaging derived information on the structural integrity of the nTMS-based tractography results improves the predictive power for postoperative motor outcome. Utilizing a second subcortical ROI which is specifically seeded based on the color-coded FA map increases the tracking quality of the CST independently of the examiner's experience. Further prospective studies are needed to validate the nTMS-based prediction of the patient's outcome. Keywords: Navigated transcranial magnetic stimulation (nTMS), Brain tumor surgery, Glioma, Motor outcome, Diffusion tensor imaging, Fractional anisotropy, Apparent diffusion coefficient

Navigated transcranial magnetic stimulation (nTMS) has recently been introduced as a non-invasive tool for functional mapping of cortical language areas prior to surgery. It correlates well with intraoperative neurophysiological monitoring findings, allowing defining the best surgical strategy to preserve cortical language areas during surgery for language-eloquent tumors. Nevertheless, nTMS allows only for cortical mapping and postoperative language deficits are often caused by injury to subcortical language pathways. Nowadays, the only way to preoperatively visualize language subcortical white matter tracts consists in DTI fiber tracking (DTI-FT). However, standard DTI-FT is based on anatomical landmarks that vary interindividually and can be obscured by the presence of the tumor itself. It has been demonstrated that combining nTMS with DTI-FT allows for a more reliable visualization of the motor pathway in brain tumor patients. Nevertheless, no description about such a combination has been reported for the language network. The aim of the present study is to describe and assess the feasibility and reliability of using cortical seeding areas defined by error type-specific nTMS language mapping (nTMS-positive spots) to perform DTI-FT in patients affected by language-eloquent brain tumors. We describe a novel technique for a nTMS-based DTI-FT to visualize the complex cortico-subcortical connections of the language network. We analyzed quantitative findings, such as fractional anisotropy values and ratios, and the number of visualized connections of nTMS-positive spots with subcortical pathways, and we compared them with results obtained by using the standard DTI-FT technique. We also analyzed the functional concordance between connected cortical nTMS-positive spots and subcortical pathways, and the likelihood of connection for nTMS-positive versus nTMS-negative cortical spots. We demonstrated, that the nTMS-based approach, especially what we call the single-spot strategy, is able to provide a reliable and more detailed reconstruction of the complex cortico-subcortical language network as compared to the standard DTI-FT. We believe this technique represents a beneficial new strategy for customized preoperative planning in patients affected by tumors in presumed language eloquent location, providing anatomo-functional information to plan language-preserving surgery.

Lutz Weise, Olaf Suess, Thomas Picht, Theodoros KombosNeurochirurgische Klinik, Charité – Universitätsmedizin Berlin, Berlin, GermanyObjective: Transpedicular screws are commonly and successfully used for posterior fixation in spinal instability, but their insertion remains challenging. Even using navigation techniques, there is a misplacement rate of up to 11%. The aim of this study was to assess the accuracy of a novel pedicle screw system.Methods: Thoracic and lumbar fusions were performed on 67 consecutive patients for tumor, trauma, degenerative disease or infection. A total of 326 pedicular screws were placed using a novel wire-guided, cannulated, polyaxial screw system (XIA Precision®, Stryker). The accuracy of placement was assessed post operatively by CT scan, and the patients were followed-up clinically for a mean of 16 months.Results: The total medio-caudal pedicle wall perforation rate was 9.2% (30/326). In 19 of these 30 cases a cortical breakthrough of less than 2 mm occurred. The misplacement rate (defined as a perforation of 2 mm or more) was 3.37% (11/326). Three of these 11 screws needed surgical revision due to neurological symptoms or CSF leakage. There have been no screw breakages or dislocations over the follow up-period.Conclusion: We conclude that the use of this cannulated screw system for the placement of pedicle screws in the thoracic and lumbar spine is accurate and safe. The advantages of this technique include easy handling without a time-consuming set up. Considering the incidence of long-term screw breakage, further investigation with a longer follow-up period is necessary.Keywords: spinal instrumentation, pedicle screws, misplacement, pedicle wall perforation