Publications by authors named "Thomas Picht"

81 Publications

Does stereoscopic imaging improve the memorization of medical imaging by neurosurgeons? Experience of a single institution.

Neurosurg Rev 2021 Sep 22. Epub 2021 Sep 22.

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurosurgery, Charitéplatz 1, 10117, Berlin, Germany.

Stereoscopic imaging has increasingly been used in anatomical teaching and neurosurgery. The aim of our study was to analyze the potential utility of stereoscopic imaging as a tool for memorizing neurosurgical patient cases compared to conventional monoscopic visualization. A total of 16 residents and 6 consultants from the Department of Neurosurgery at Charité - Universitätsmedizin Berlin were recruited for the study. They were divided into two equally experienced groups. A comparative analysis of both imaging modalities was conducted in which four different cases were assessed by the participants. Following the image assessment, two questionnaires, one analyzing the subjective judgment using the 5-point Likert Scale and the other assessing the memorization and anatomical accuracy, were completed by all participants. Both groups had the same median year of experience (5) and stereoacuity (≤ 75 s of arc). The analysis of the first questionnaire demonstrated significant subjective superiority of the monoscopic imaging in evaluation of the pathology (median: monoscopic: 4; stereoscopic: 3; p = 0.020) and in handling of the system (median: monoscopic: 5; stereoscopic: 2; p < 0.001). The second questionnaire showed that the anatomical characterization of the pathologies was comparable between both visualization methods. Most participants rated the stereoscopic visualization as worse compared to the monoscopic visualization, probably due to a lack of familiarity with the newer technique. Stereoscopic imaging, however, was not objectively inferior to traditional monoscopic imaging for anatomical comprehension. Further methodological developments and incorporation in routine clinical workflows will most likely enhance the usability and acceptance of stereoscopic visualization.
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http://dx.doi.org/10.1007/s10143-021-01623-0DOI Listing
September 2021

Lesion-symptom mapping of language impairments in patients suffering from left perisylvian gliomas.

Cortex 2021 Sep 2;144:1-14. Epub 2021 Sep 2.

Cluster of Excellence: "Matters of Activity. Image Space Material", Humboldt University, Berlin, Germany; Freie Universität Berlin, Brain Language Laboratory, Department of Philosophy and Humanities, Berlin, Germany; Medical School OWL, Bielefeld University, Bielefeld, Germany.

Brain tumors cause local structural impairments of the cerebral network. Moreover, brain tumors can also affect functional brain networks more distant from the lesion. In this study, we analyzed the impact of glioma WHO grade II-IV tumors on grey and white matter in relation to impaired language function. In a retrospective analysis of 60 patients, 14 aphasic and 46 non-aphasic, voxel-based lesion-symptom mapping (VLSM) was used to identify tumor induced lesions in grey (GM) and white matter (WM) related to patients' performance in subtests of the Aachen Aphasia Test (AAT). Significant clusters were analyzed for atlas-based grey and white matter involvements in relation to different linguistic modalities. VLSM analysis indicated significant contribution of a posterior perisylvian cluster covering WM and GM to AAT performance averaged across subtests. When considering individual AAT subtests, a substantial overlap between significant clusters for analysis of the token test, picture naming and language comprehension results could be observed. The WM-cluster intersections reflect the overall importance of the perisylvian area in language function, similarly to GM participations. Especially the constant high percentages of Heschl's gyrus, superior temporal gyrus, inferior longitudinal and middle longitudinal fascicles, but also arcuate and inferior fronto-occipital fascicles highlight the importance of the posterior perisylvian area for language function.
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http://dx.doi.org/10.1016/j.cortex.2021.08.002DOI Listing
September 2021

Bicentric validation of the navigated transcranial magnetic stimulation motor risk stratification model.

J Neurosurg 2021 Sep 17:1-13. Epub 2021 Sep 17.

1Department of Neurosurgery, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin.

Objective: The authors sought to validate the navigated transcranial magnetic stimulation (nTMS)-based risk stratification model. The postoperative motor outcome in glioma surgery may be preoperatively predicted based on data derived by nTMS. The tumor-to-tract distance (TTD) and the interhemispheric resting motor threshold (RMT) ratio (as a surrogate parameter for cortical excitability) emerged as major factors related to a new postoperative deficit.

Methods: In this bicentric study, a consecutive prospectively collected cohort underwent nTMS mapping with diffusion tensor imaging (DTI) fiber tracking of the corticospinal tract prior to surgery of motor eloquent gliomas. The authors analyzed whether the following items were associated with the patient's outcome: patient characteristics, TTD, RMT value, and diffusivity parameters (fractional anisotropy [FA] and apparent diffusion coefficient [ADC]). The authors assessed the validity of the published risk stratification model and derived a new model.

Results: A new postoperative motor deficit occurred in 36 of 165 patients (22%), of whom 20 patients still had a deficit after 3 months (13%; n3 months = 152). nTMS-verified infiltration of the motor cortex as well as a TTD ≤ 8 mm were confirmed as risk factors. No new postoperative motor deficit occurred in patients with TTD > 8 mm. In contrast to the previous risk stratification, the RMT ratio was not substantially correlated with the motor outcome, but high RMT values of both the tumorous and healthy hemisphere were associated with worse motor outcome. The FA value was negatively associated with worsening of motor outcome. Accuracy analysis of the final model showed a high negative predictive value (NPV), so the preoperative application may accurately predict the preservation of motor function in particular (day of discharge: sensitivity 47.2%, specificity 90.7%, positive predictive value [PPV] 58.6%, NPV 86.0%; 3 months: sensitivity 85.0%, specificity 78.8%, PPV 37.8%, NPV 97.2%).

Conclusions: This bicentric validation analysis further improved the model by adding the FA value of the corticospinal tract, demonstrating the relevance of nTMS/nTMS-based DTI fiber tracking for clinical decision making.
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http://dx.doi.org/10.3171/2021.3.JNS2138DOI Listing
September 2021

Evaluation of a Novel Three-Dimensional Robotic Digital Microscope (Aeos) in Neurosurgery.

Cancers (Basel) 2021 Aug 25;13(17). Epub 2021 Aug 25.

Department of Neurosurgery, University Hospital Frankfurt, 60528 Frankfurt am Main, Germany.

Objective: Current literature debates the role of newly developed three-dimensional (3D) Exoscopes in the daily routine of neurosurgical practice. So far, only a small number of cadaver lab studies or case reports have examined the novel Aesculap Aeos Three-Dimensional Robotic Digital Microscope. This study aims to evaluate the grade of satisfaction and intraoperative handling of this novel system in neurosurgery.

Methods: Nineteen neurosurgical procedures (12 cranial, 6 spinal and 1 peripheral nerve) performed over 9 weeks using the Aeos were analyzed. Ten neurosurgeons of varying levels of training were included after undergoing device instruction and training. Following every surgery, a questionnaire consisting of 43 items concerning intraoperative handling was completed. The questionnaires were analyzed using descriptive statistics.

Results: No intraoperative complications occurred. Surgical satisfaction was ranked high (78.95%). In total, 84.21% evaluated surgical ergonomics as satisfactory, while 78.95% of the surgeons would like to use this system frequently. Image quality, independent working zoom function and depth of field were perceived as suboptimal by several neurosurgeons.

Conclusion: The use of Aeos is feasible and safe in microsurgical procedures, and surgical satisfaction was ranked high among most neurosurgeons in our study. The system might offer advanced ergonomic conditions in comparison to conventional ocular-based microscopes.
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http://dx.doi.org/10.3390/cancers13174273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428371PMC
August 2021

Motor excitability in bilateral moyamoya vasculopathy and the impact of revascularization.

Neurosurg Focus 2021 09;51(3):E7

1Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurosurgery, Berlin.

Objective: Motor cortical dysfunction has been shown to be reversible in patients with unilateral atherosclerotic disease after cerebral revascularization. Moyamoya vasculopathy (MMV) is a rare bilateral stenoocclusive cerebrovascular disease. The aim of this study was to analyze the corticospinal excitability and the role of bypass surgery in restoring cortical motor function in patients by using navigated transcranial magnetic stimulation (nTMS).

Methods: Patients with bilateral MMV who met the criteria for cerebral revascularization were prospectively included. Corticospinal excitability, cortical representation area, and intracortical inhibition and facilitation were assessed by nTMS for a small hand muscle (first dorsal interosseous) before and after revascularization. The clinically and/or hemodynamically more severely affected hemisphere was operated first as the leading hemisphere. Intra- and interhemispheric differences were analyzed before and after direct or combined revascularization.

Results: A total of 30 patients with bilateral MMV were examined by nTMS prior to and after revascularization surgery. The corticospinal excitability was higher in the leading hemisphere compared with the non-leading hemisphere prior to revascularization. This hyperexcitability was normalized after revascularization as demonstrated in the resting motor threshold ratio of the hemispheres (preoperative median 0.97 [IQR 0.89-1.08], postoperative median 1.02 [IQR 0.94-1.22]; relative effect = 0.61, p = 0.03). In paired-pulse paradigms, a tendency for a weaker inhibition of the leading hemisphere was observed compared with the non-leading hemisphere. Importantly, the paired paradigm also demonstrated approximation of excitability patterns between the two hemispheres after surgery.

Conclusions: The study results suggested that, in the case of a bilateral chronic ischemia, a compensation mechanism between both hemispheres seemed to exist that normalized after revascularization surgery. A potential role of nTMS in predicting the efficacy of revascularization must be further assessed.
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http://dx.doi.org/10.3171/2021.6.FOCUS21280DOI Listing
September 2021

Distinct approaches to language pathway tractography: comparison of anatomy-based, repetitive navigated transcranial magnetic stimulation (rTMS)-based, and rTMS-enhanced diffusion tensor imaging-fiber tracking.

J Neurosurg 2021 Jul 30:1-12. Epub 2021 Jul 30.

Departments of1Neurosurgery and.

Objective: Visualization of subcortical language pathways by means of diffusion tensor imaging-fiber tracking (DTI-FT) is evolving as an important tool for surgical planning and decision making in patients with language-suspect brain tumors. Repetitive navigated transcranial magnetic stimulation (rTMS) cortical language mapping noninvasively provides additional functional information. Efforts to incorporate rTMS data into DTI-FT are promising, but the lack of established protocols makes it hard to assess clinical utility. The authors performed DTI-FT of important language pathways by using five distinct approaches in an effort to evaluate the respective clinical usefulness of each approach.

Methods: Thirty patients with left-hemispheric perisylvian lesions underwent preoperative rTMS language mapping and DTI. FT of the principal language tracts was conducted according to different strategies: Ia, anatomical landmark based; Ib, lesion-focused landmark based; IIa, rTMS based; IIb, rTMS based with postprocessing; and III, rTMS enhanced (based on a combination of structural and functional data). The authors analyzed the respective success of each method in revealing streamlines and conducted a multinational survey with expert clinicians to evaluate aspects of clinical utility.

Results: The authors observed high usefulness and accuracy ratings for anatomy-based approaches (Ia and Ib). Postprocessing of rTMS-based tractograms (IIb) led to more balanced perceived information content but did not improve the usefulness for surgical planning and risk assessment. Landmark-based tractography (Ia and Ib) was most successful in delineating major language tracts (98% success), whereas rTMS-based tractography (IIa and IIb) frequently failed to reveal streamlines and provided less complete tractograms than the landmark-based approach (p < 0.001). The lesion-focused landmark-based (Ib) and the rTMS-enhanced (III) approaches were the most preferred methods.

Conclusions: The lesion-focused landmark-based approach (Ib) achieved the best ratings and enabled visualization of the principal language tracts in almost all cases. The rTMS-enhanced approach (III) was positively evaluated by the experts because it can reveal cortico-subcortical connections, but the functional relevance of these connections is still unclear. The use of regions of interest derived solely from cortical rTMS mapping (IIa and IIb) leads to cluttered images that are of limited use in clinical practice.
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http://dx.doi.org/10.3171/2020.12.JNS204028DOI Listing
July 2021

Clinical implementation of a 3D4K-exoscope (Orbeye) in microneurosurgery.

Neurosurg Rev 2021 Jun 18. Epub 2021 Jun 18.

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.

Exoscopic surgery promises alleviation of physical strain, improved intraoperative visualization and facilitation of the clinical workflow. In this prospective observational study, we investigate the clinical usability of a novel 3D4K-exoscope in routine neurosurgical interventions. Questionnaires on the use of the exoscope were carried out. Exemplary cases were additionally video-documented. All participating neurosurgeons (n = 10) received initial device training. Changing to a conventional microscope was possible at all times. A linear mixed model was used to analyse the impact of time on the switchover rate. For further analysis, we dichotomized the surgeons in a frequent (n = 1) and an infrequent (n = 9) user group. A one-sample Wilcoxon signed rank test was used to evaluate, if the number of surgeries differed between the two groups. Thirty-nine operations were included. No intraoperative complications occurred. In 69.2% of the procedures, the surgeon switched to the conventional microscope. While during the first half of the study the conversion rate was 90%, it decreased to 52.6% in the second half (p = 0.003). The number of interventions between the frequent and the infrequent user group differed significantly (p = 0.007). Main reasons for switching to ocular-based surgery were impaired hand-eye coordination and poor depth perception. The exoscope investigated in this study can be easily integrated in established neurosurgical workflows. Surgical ergonomics improved compared to standard microsurgical setups. Excellent image quality and precise control of the camera added to overall user satisfaction. For experienced surgeons, the incentive to switch from ocular-based to exoscopic surgery greatly varies.
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http://dx.doi.org/10.1007/s10143-021-01577-3DOI Listing
June 2021

Preoperative nTMS and Intraoperative Neurophysiology - A Comparative Analysis in Patients With Motor-Eloquent Glioma.

Front Oncol 2021 21;11:676626. Epub 2021 May 21.

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.

Background: The 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.

Objective: To analyze to what extent preoperative nTMS motor risk stratification can improve the interpretation of IOM phenomena.

Methods: In 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).

Results: Thirty-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, RMT <90%/>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.

Conclusions: The 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.
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http://dx.doi.org/10.3389/fonc.2021.676626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175894PMC
May 2021

Navigated repetitive transcranial magnetic stimulation improves the outcome of postsurgical paresis in glioma patients - A randomized, double-blinded trial.

Brain Stimul 2021 Jul-Aug;14(4):780-787. Epub 2021 May 11.

Department of Neurosurgery, Technical University of Munich, Germany, School of Medicine, Klinikum Rechts der Isar, Germany; TUM Neuroimaging Center, Technical University of Munich, Germany, School of Medicine, Klinikum Rechts der Isar, Germany. Electronic address:

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.
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http://dx.doi.org/10.1016/j.brs.2021.04.026DOI Listing
May 2021

Redefining standards-response to: introductions of technological innovations in neurosurgery.

Acta Neurochir (Wien) 2021 08 4;163(8):2095-2096. Epub 2021 May 4.

Image Guidance Lab, Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.

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http://dx.doi.org/10.1007/s00701-021-04853-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270815PMC
August 2021

No Impact of Functional Connectivity of the Motor System on the Resting Motor Threshold: A Replication Study.

Front Neurosci 2021 31;15:627445. Epub 2021 Mar 31.

Charité - Universitätsmedizin Berlin, Department of Neurosurgery, Berlin, Germany.

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 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.
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http://dx.doi.org/10.3389/fnins.2021.627445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044353PMC
March 2021

Detecting Corticospinal Tract Impairment in Tumor Patients With Fiber Density and Tensor-Based Metrics.

Front Oncol 2020 27;10:622358. Epub 2021 Jan 27.

Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Berlin, Germany.

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.
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http://dx.doi.org/10.3389/fonc.2020.622358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873606PMC
January 2021

Preoperative transcranial magnetic stimulation for picture naming is reliable in mapping segments of the arcuate fasciculus.

Brain Commun 2020 29;2(2):fcaa158. Epub 2020 Sep 29.

Department of Neurosurgery, Charité University Hospital, Berlin, Germany.

In preoperative planning for neurosurgery, both anatomical (diffusion imaging tractography) and functional tools (MR-navigated transcranial magnetic stimulation) are increasingly used to identify and preserve eloquent language structures specific to individuals. Using these tools in healthy adults shows that speech production errors occur mainly in perisylvian cortical sites that correspond to subject-specific terminations of the major language pathway, the arcuate fasciculus. It is not clear whether this correspondence remains in oncological patients with altered tissue. We studied a heterogeneous cohort of 30 patients (fourteen male, mean age 44), undergoing a first or second surgery for a left hemisphere brain tumour in a language-eloquent region, to test whether speech production errors induced by preoperative transcranial magnetic stimulation had consistent anatomical correspondence to the arcuate fasciculus. We used navigated repetitive transcranial magnetic stimulation during picture naming and recorded different perisylvian sites where transient interference to speech production occurred. Spherical deconvolution diffusion imaging tractography was performed to map the direct fronto-temporal and indirect (fronto-parietal and parieto-temporal) segments of the arcuate fasciculus in each patient. Speech production errors were reported in all patients when stimulating the frontal lobe, and in over 90% of patients in the parietal lobe. Errors were less frequent in the temporal lobe (54%). In all patients, at least one error site corresponded to a termination of the arcuate fasciculus, particularly in the frontal and parietal lobes, despite distorted anatomy due to a lesion and/or previous resection. Our results indicate that there is strong correspondence between terminations of the arcuate fasciculus and speech errors. This indicates that white matter anatomy may be a robust marker for identifying functionally eloquent cortex, particularly in the frontal and parietal lobe. This knowledge may improve targets for preoperative mapping of language in the neurosurgical setting.
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http://dx.doi.org/10.1093/braincomms/fcaa158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7846168PMC
September 2020

Towards a tractography-based risk stratification model for language area associated gliomas.

Neuroimage Clin 2021 25;29:102541. Epub 2020 Dec 25.

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Cluster of Excellence: "Matters of Activity. Image Space Material", Humboldt University, Berlin, Germany.

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.
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http://dx.doi.org/10.1016/j.nicl.2020.102541DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785953PMC
June 2021

Hands-free Adjustment of the Microscope in Microneurosurgery.

World Neurosurg 2021 04 29;148:e155-e163. Epub 2020 Dec 29.

Department of Neurosurgery, Charité, Universitätsmedizin Berlin, Berlin, Germany.

Background: In microneurosurgery, the operating microscope plays a vital role. The classical neurosurgical operation is bimanual, that is, the microsurgical instruments are operated with both hands. Often, operations have to be carried out in narrow corridors at the depth of several centimeters. With current technology, the operator must manually adjust the field of view during surgery-which poses a disruption in the operating flow. Until now, technical adjuncts existed in the form of a mouthpiece to move the stereo camera unit or voice commands and foot pedals to control other interaction tasks like optical configuration. However, these have not been widely adopted due to usability issues. This study tests 2 novel hands-free interaction concepts based on head positioning and gaze tracking as an attempt to reduce the disruption during microneurosurgery and increase the efficiency of the user.

Methods: Technical equipment included the Pentero 900 microscope (Carl Zeiss Microscopy GmbH, Jena, Germany), HTC Vive Pro (HTC, Taoyuan District (HQ), Taiwan), and an inbuilt 3D-printed target probe. Eleven neurosurgeons including 7 residents and 4 consultants participated in the study. The tasks created for this study were with the intention to mimic real microneurosurgical tasks to maintain applicative accuracy while testing the interaction concepts. The tasks involved visualization system adjustment to the specific target and touching the target. The first trial was conducted in a virtual reality setting applying the novel hands-free interaction concepts, and the second trial was conducted performing the same tasks on a 3D-printed target probe using manual field of view adjustment. The participants completed both trials with the same predetermined tasks, in order to validate the feasibility of the novel technology. The data collected for this study were obtained with the help of review protocols, detailed post-trial interviews, video and audio recordings, along with time measurements while performing the tasks.

Results: The user study conducted at the Charité Hospital in Berlin found that the gaze-tracking and head-positioning- based microscope adjustment were 18% and 29% faster, respectively, than the classical bimanual adjustment of the microscope. Focused user interviews showed the users' proclivity for the new interaction concepts, as they offered minimal disruption between the simultaneous target selection and camera position adjustment.

Conclusions: The hands-free interaction concepts presented in this study demonstrated a more efficient execution of the microneurosurgical tasks than the classical manual microscope and were assessed to be more preferable by both residents and consultant neurosurgeons.
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http://dx.doi.org/10.1016/j.wneu.2020.12.092DOI Listing
April 2021

Support vector machine based aphasia classification of transcranial magnetic stimulation language mapping in brain tumor patients.

Neuroimage Clin 2021 24;29:102536. Epub 2020 Dec 24.

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany; Cluster of Excellence: "Matters of Activity. Image Space Material", Humboldt Universität zu Berlin, Berlin, Germany.

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.
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http://dx.doi.org/10.1016/j.nicl.2020.102536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772815PMC
June 2021

Pediatric navigated transcranial magnetic stimulation motor and language mapping combined with diffusion tensor imaging tractography: clinical experience.

J Neurosurg Pediatr 2020 Jul 24:1-11. Epub 2020 Jul 24.

3Pediatric Neurosurgery, Charité University Medicine, Berlin, Germany.

Objective: In adults, navigated transcranial magnetic stimulation (nTMS) has been established as a preoperative examination method for brain tumors in motor- and language-eloquent locations. However, the clinical relevance of nTMS in children with brain tumors is still unclear. Here, the authors present their initial experience with nTMS-based surgical planning and family counseling in pediatric cases.

Methods: The authors analyzed the feasibility of nTMS and its influence on counseling and surgical strategy in a prospective study conducted between July 2017 and September 2019. The main inclusion criterion was a potential benefit from functional mapping data derived from nTMS and/or nTMS-enhanced tractography in pediatric patients who presented to the authors' department prior to surgery for lesions close to motor- and/or speech-eloquent areas. The study was undertaken in 14 patients (median age 7 years, 8 males) who presented with different brain lesions.

Results: Motor mapping combined with cortical seed area definition could be performed in 10 children (71%) to identify the corticospinal tract by additional diffusion tensor imaging (DTI). All motor mappings could be performed successfully without inducing relevant side effects. In 7 children, nTMS language mapping was performed to detect language-relevant cortical areas and DTI fiber tractography was performed to visualize the individual language network. nTMS examination was not possible in 4 children because of lack of compliance (n = 2), syncope (n = 1), and preexisting implant (n = 1). After successful mapping, the spatial relation between lesion and functional tissue was used for surgical planning in all 10 patients, and 9 children underwent nTMS-DTI integrated neuronavigation. No surgical complications or unexpected neurological deterioration was observed. In all successful nTMS cases, better function-based counseling was offered to the families. In 6 of 10 patients the surgical strategy was adapted according to nTMS data, and in 6 of 10 cases the extent of resection (EOR) was redefined.

Conclusions: nTMS and DTI fiber tracking were feasible for the majority of children. Presurgical counseling as well as surgical planning for the approach and EOR were improved by the nTMS examination results. nTMS in combination with DTI fiber tracking can be regarded as beneficial for neurosurgical procedures in eloquent areas in the pediatric population.
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http://dx.doi.org/10.3171/2020.4.PEDS20174DOI Listing
July 2020

Incidence and linguistic quality of speech errors: a comparison of preoperative transcranial magnetic stimulation and intraoperative direct cortex stimulation.

J Neurosurg 2020 May 29;134(5):1409-1418. Epub 2020 May 29.

Departments of1Neurosurgery and.

Objective: Given the interindividual variance of functional language anatomy, risk prediction based merely on anatomical data is insufficient in language area-related brain tumor surgery, suggesting the need for direct cortical and subcortical mapping during awake surgery. Reliable, noninvasive preoperative methods of language localization hold the potential for reducing the necessity for awake procedures and may improve patient counseling and surgical planning. Repetitive navigated transcranial magnetic stimulation (rnTMS) is an evolving tool for localizing language-eloquent areas. The aim of this study was to investigate the reliability of rnTMS in locating cortical language sites.

Methods: Twenty-five patients with brain tumors in speech-related areas were prospectively evaluated with preoperative rnTMS (5 Hz, train of five, average 105% resting motor threshold) and navigated direct cortical stimulation (DCS; bipolar, 50 Hz, 6-8 mA, 200-μsec pulse width) during awake surgeries employing a picture-naming task. Positive and negative stimulation spots within the craniotomy were documented in the same MRI data set. TMS and DCS language-positive areas were compared with regard to their spatial overlap, their allocation in a cortical parcellation system, and their linguistic qualities.

Results: There were over twofold more positive language spots within the exposed area on rnTMS than on DCS. The comparison of positive rnTMS and DCS (ground truth) overlaps revealed low sensitivity (35%) and low positive predictive value (16%) but high specificity (90%) and high negative predictive value (96%). Within the overlaps, there was no correlation in error quality. On DCS, 73% of language-positive spots were located in the pars opercularis and pars triangularis of the frontal operculum and 24% within the supramarginal gyrus and dorsal portion of the superior temporal gyrus, while on rnTMS language positivity was distributed more evenly over a large number of gyri.

Conclusions: The current protocol for rnTMS for language mapping identified language-negative sites with good dependability but was unable to reliably detect language-positive spots. Further refinements of the technique will be needed to establish rnTMS language mapping as a useful clinical tool.
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http://dx.doi.org/10.3171/2020.3.JNS193085DOI Listing
May 2020

Monitor-based exoscopic 3D4k neurosurgical interventions: a two-phase prospective-randomized clinical evaluation of a novel hybrid device.

Acta Neurochir (Wien) 2020 12 19;162(12):2949-2961. Epub 2020 May 19.

Department of Neurosurgery, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.

Background: Promoting a disruptive innovation in microsurgery, exoscopes promise alleviation of physical strain and improved image quality through digital visualization during microneurosurgical interventions. This study investigates the impact of a novel 3D4k hybrid exoscope (i.e., combining digital and optical visualization) on surgical performance and team workflow in preclinical and clinical neurosurgical settings.

Methods: A pre-clinical workshop setting has been developed to assess usability and implementability through skill-based scenarios (neurosurgical participants n = 12). An intraoperative exploration in head and spine surgery (n = 9) and a randomized clinical study comparing ocular and monitor mode in supratentorial brain tumor cases (n = 20) followed within 12 months. Setup, procedure, case characteristics, surgical performance, and user experience have been analyzed for both ocular group (OG) and monitor group (MG).

Results: Brain tumor cases using frontal, frontoparietal, or temporal approaches have been identified as favorable use cases for introducing exoscopic neurosurgery. Mean monitor distance and angle were 180 cm and 10°. Surgical ergonomics when sitting improved significantly in MG compared with OG (P = .03). Hand-eye coordination required familiarization in MG. Preclinical data showed a positive correlation between lateral camera inclination and impact on hand-eye coordination (r = 0.756, P = .01). There was no significant added surgical time in MG. Image quality in current generation 3D4k monitors has been rated inferior to optic visualization yet awaits updates.

Conclusions: The hybrid exoscopic device can be integrated into established neurosurgical workflows. Currently, exoscopic interventions seem most suited for cranial tumor surgery in lesions that are not deep-seated. Ergonomics improve in monitor mode compared to conventional microsurgery.
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http://dx.doi.org/10.1007/s00701-020-04361-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593287PMC
December 2020

Development and initial evaluation of a novel simulation model for comprehensive brain tumor surgery training.

Acta Neurochir (Wien) 2020 08 8;162(8):1957-1965. Epub 2020 May 8.

Department of Neurosurgery, Charité, Universitätsmedizin Berlin, Charitéplatz 1, 10117, Berlin, Germany.

Background: Increasing technico-manual complexity of procedures and time constraints necessitates effective neurosurgical training. For this purpose, both screen- and model-based simulations are under investigation. Approaches including 3D printed brains, gelatin composite models, and virtual environments have already been published. However, quality of brain surgery simulation is limited due to discrepancies in visual and haptic experience. Similarly, virtual training scenarios are still lacking sufficient real-world resemblance. In this study, we introduce a novel simulator for realistic neurosurgical training that combines real brain tissue with 3D printing and augmented reality.

Methods: Based on a human CT scan, a skull base and skullcap were 3D printed and equipped with an artificial dura mater. The cerebral hemispheres of a calf's brain were placed in the convexity of the skullcap and tumor masses composed of aspic, water, and fluorescein were injected in the brain. The skullcap and skull base were placed on each other, glued together, and filled up with an aspic water solution for brain fixation. Then, four surgical scenarios were performed in the operating room as follows: (1) simple tumor resection, (2) complex tumor resection, (3) navigated biopsy via burr hole trepanation, and (4) retrosigmoidal craniotomy. Neuronavigation, augmented reality, fluorescence, and ocular-as well as screen-based (exoscopic)-surgery were available for the simulator training. A total of 29 participants performed at least one training scenario of the simulator and completed a 5-item Likert-like questionnaire as well as qualitative interviews. The questionnaire assessed the realism of the tumor model, skull, and brain tissue as well as the capability for training purposes.

Results: Visual and sensory realism of the skull and brain tissue were rated,"very good," while the sensory and visual realism of the tumor model were rated "good." Both overall satisfaction with the model and eligibility of the microscope and neurosurgical instruments for training purposes were rated with "very good." However, small size of the calf's brain, its limited shelf life, and the inability to simulate bleedings due to the lack of perfusion were significant drawbacks.

Conclusion: The combination of 3D printing and real brain tissue provided surgical scenarios with very good real-life resemblance. This novel neurosurgical model features a versatile setup for surgical skill training and allows for efficient training of technological support like image and fluorescence guidance, exoscopic surgery, and robotic technology.
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http://dx.doi.org/10.1007/s00701-020-04359-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360639PMC
August 2020

The functional relevance of dorsal motor systems for processing tool nouns- evidence from patients with focal lesions.

Neuropsychologia 2020 04 14;141:107384. Epub 2020 Feb 14.

Freie Universität Berlin, Brain Language Laboratory, Department of Philosophy and Humanities, Berlin, Germany; Humboldt Universität zu Berlin, Cluster of Excellence Matters of Activity, Image Space Material, Berlin, Germany; Einstein Center for Neurosciences Berlin, Berlin, Germany; Humboldt Universität zu Berlin, Berlin School of Mind and Brain, Berlin, Germany.

This study asks whether lesions in different parts of the brain have different effects on the processing of words typically used to refer to objects with and without action affordances, for example tools and animal-related nouns. A cohort of neurological patients with focal lesions participated in a lexical decision paradigm where nouns semantically related to tools, foods and animals were presented along with matched pseudo-words. Differences in semantic features between the categories were confirmed using extensive semantic ratings whereas all semantic word categories were matched for relevant psycholinguistic variables. In a data-driven region of interest analysis, lesions in dorsal pre- and postcentral grey and white matter areas were associated to specific performance deficits for tool nouns when compared to animal nouns. In contrast, patients with lesions primarily affecting perisylvian inferior-frontal and/or temporal regions presented similar deficits across all semantic word categories tested and likewise a group of age and education matched healthy control participants did not show any category specific differences. These findings falsify brain language models denying the fronto-parietal cortex' role in word recognition and semantic understanding. They are best accounted for by frameworks that acknowledge a role of sensorimotor cortex in the semantic processing of action-related words.
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http://dx.doi.org/10.1016/j.neuropsychologia.2020.107384DOI Listing
April 2020

1 Hz Repetitive Transcranial Magnetic Stimulation of the Primary Motor Cortex: Impact on Excitability and Task Performance in Healthy Subjects.

J Neurol Surg A Cent Eur Neurosurg 2020 Mar 11;81(2):147-154. Epub 2020 Feb 11.

Department of Neurosurgery, Charité Universitatsmedizin Berlin, Berlin, Germany.

Objective:  Neuronavigated repetitive transcranial stimulation (rTMS) at a frequency of 1 Hz was shown to reduce excitability in underlying brain areas while increasing excitability in the opposite hemisphere. In stroke patients, this principle is used to normalize activity between the lesioned and healthy hemispheres and to facilitate rehabilitation. However, standardization is lacking in applied protocols, and there is a poor understanding of the underlying physiologic mechanisms. Furthermore, the influence of hemispheric dominance on the intervention has not been studied before. A systematic evaluation of the effects in healthy subjects would deepen the understanding of these mechanisms and offer insights into ways to improve the intervention.

Methods:  Twenty healthy subjects underwent five 15-minute sessions of neuronavigated rTMS or sham stimulation over their dominant or nondominant motor cortex. Dominance was assessed with the Edinburgh Handedness Inventory. Changes in both hemispheres were measured using behavioral parameters (finger tapping, grip force, and finger dexterity) and TMS measures (resting motor threshold, recruitment curve, motor area, and cortical silent period).

Results:  All subjects tolerated the stimulation well. A pronounced improvement was noted in finger tapping scores over the nonstimulated hemisphere as well as a nonsignificant reduction of the cortical silent period in the stimulated hemisphere, indicating a differential effect of the rTMS on both hemispheres. Grip force remained at the baseline level in the rTMS group while decreasing in the sham group, suggesting the rTMS counterbalanced the effects of fatigue. Lastly, dominance did not influence any of the observed effects.

Conclusions:  This study shows the capability of the applied low-frequency rTMS protocol to modify excitability of underlying brain areas as well as the contralateral hemisphere. It also highlights the need for a better understanding of underlying mechanisms and the identification of predictors for responsiveness to rTMS. However, results should be interpreted with caution because of the small sample size.
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http://dx.doi.org/10.1055/s-0040-1701624DOI Listing
March 2020

Multivariable non-invasive association of isocitrate dehydrogenase mutational status in World Health Organization grade II and III gliomas with advanced magnetic resonance imaging T2 mapping techniques.

Neuroradiol J 2020 Apr 19;33(2):160-168. Epub 2020 Jan 19.

Department of Neuroradiology, Charite University Hospital Berlin, Germany.

Aim: To investigate multivariable analyses for noninvasive association of the isocitrate dehydrogenase (IDH) mutational status in grade II and III gliomas including evaluation of T2 mapping-sequences.

Methods: Magnetic resonance imaging (MRI) examinations with histopathologically proven World Health Organization grade II and III gliomas were retrospectively enrolled. Multivariate receiver operating characteristics (ROC) analyses to associate IDH mutational status were performed containing quantitative T2 mapping analyses and qualitative characteristics (sex, age, localization, heterogeneity, oedema, necrosis and diameter). Relaxation times were calculated pixelwise by means of standardized ROI analyses. Interobserver variability also was tested.

Results: Out of 32 patients (mean age: 50.7 years; range: 32-83), nine had grade II gliomas and 24 grade III, while 59.5% showed a positive IDH mutated state (IDHm) and 40.5% were wildtype (IDHw). Multivariable ROC analyses were calculated for relaxation time and range, localization and age with a cumulative 0.955 area under the curve (AUC) ( < 0.001), while central T2-relaxation time had by far the highest single variable sensitivity (AUC: 0.873; range: 0.762; age: 0.809; localization: 0.713). Age (cut off: 49 years;  = 0.031) and localization ( = 0.014) were the only qualitative parameters found to be significant as IDHw gliomas were older and IDHm gliomas were preferentially located fronto-temporal.

Conclusions: This is the first study evaluating quantitative T2 mapping sequences for association of the IDH mutational status in grade II and III gliomas demonstrating an association between relaxation time and mutational status. Analyses of T2 mapping relaxation times may even be suitable for predicting the correct IDH mutational state. Prognostic accuracy increases significantly in predicting the correct mutational state when combing T2 relaxation time characteristics and the qualitative MRI features age and localization.
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http://dx.doi.org/10.1177/1971400919890099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140300PMC
April 2020

T2 mapping of molecular subtypes of WHO grade II/III gliomas.

BMC Neurol 2020 Jan 8;20(1). Epub 2020 Jan 8.

Department of Neuroradiology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany.

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.
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http://dx.doi.org/10.1186/s12883-019-1590-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947951PMC
January 2020

NTMS mapping of non-primary motor areas in brain tumour patients and healthy volunteers.

Acta Neurochir (Wien) 2020 02 25;162(2):407-416. Epub 2019 Nov 25.

Department of Neurosurgery, Charité University Medicine, Charitéplatz 1, Berlin, Germany.

Objective: Navigated transcranial magnetic stimulation (nTMS) has been increasingly used for presurgical cortical mapping of the primary motor cortex (M1) but remains controversial for the evaluation of non-primary motor areas (NPMA). This study investigates clinical and neurophysiological parameters in brain tumour patients and healthy volunteers to decide whether single-pulse biphasic nTMS allows to reliably elicite MEP outside from M1 or not.

Materials And Methods: Twelve brain tumour patients and six healthy volunteers underwent M1 nTMS mapping. NPMA nTMS mapping followed using 120% and 150% M1 resting motor threshold (RMT) stimulation intensity. Spearman's correlation analysis tested the association of clinical and neurophysiological parameters between M1 and NPMA mapping.

Results: A total of 88.81% of nTMS stimulations in NPMA in patients/83.87% in healthy volunteers in patients/83.87% in healthy volunteers did not result in MEPs ≥ 50 μV. Positive nTMS mapping in NPMA correlated with higher stimulation intensity and larger M1 areas in patients (120% M1 RMT SI p = 0.005/150% M1 RMT SI p = 0.198).

Conclusion: Our findings indicate that in case of positive nTMS mapping in NPMA, MEPs originate mostly from M1. For future studies, MEP parameters and TMS coil rotation should be studied closely to assess the risk for postoperative motor deterioration.
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http://dx.doi.org/10.1007/s00701-019-04086-xDOI Listing
February 2020

Estimation of the resting motor threshold (RMT) in transcranial magnetic stimulation using relative-frequency and threshold-hunting methods in brain tumor patients.

Acta Neurochir (Wien) 2019 09 8;161(9):1845-1851. Epub 2019 Jul 8.

Department of Neurosurgery, Charité - Universitätsmedizin, Charitéplatz 1, 10117, Berlin, Germany.

Background: Application of transcranial magnetic stimulation is often based on the resting motor threshold. The aim of this study was to validate recent findings on the advantage of resting motor threshold estimation using adaptive threshold-hunting algorithms over the Rossini-Rothwell method in a clinical sample and healthy subjects.

Methods: Resting motor thresholds in 115 patients with a brain tumor and 10 healthy subjects were assessed using the Rossini-Rothwell method and compared to an adaptive threshold-hunting algorithm. In healthy subjects, this measurement was repeated twice to capture test-retest reliability of both methods. Efficiency of both methods was assessed by comparing the number of pulses needed for resting motor threshold estimation.

Results: There was no significant difference between the Rossini-Rothwell method and the adaptive threshold-hunting algorithm in patients and healthy controls with limits of agreement between ± 12 V/m. There was a strong intraclass correlation and both methods showed a good test-retest reliability. However, the adaptive threshold-hunting algorithm was significantly faster.

Conclusions: The adaptive threshold-hunting algorithm was more efficient in assessing the resting motor threshold, while reaching comparable results as the Rossini-Rothwell method. Thus, our results support the advantage of adaptive threshold-hunting algorithms to determine the resting motor threshold also in a clinical sample.
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http://dx.doi.org/10.1007/s00701-019-03997-zDOI Listing
September 2019

Surgical treatment of meningiomas located in the rolandic area: the role of navigated transcranial magnetic stimulation for preoperative planning, surgical strategy, and prediction of arachnoidal cleavage and motor outcome.

J Neurosurg 2019 Jun 14:1-12. Epub 2019 Jun 14.

1Division of Neurosurgery, University of Messina, Italy; and.

Objective: Surgical treatment of convexity meningiomas is usually considered a low-risk procedure. Nevertheless, the risk of postoperative motor deficits is higher (7.1%-24.7% of all cases) for lesions located in the rolandic region, especially when an arachnoidal cleavage plane with the motor pathway is not identifiable. The authors analyzed the possible role of navigated transcranial magnetic stimulation (nTMS) for planning resection of rolandic meningiomas and predicting the presence or lack of an intraoperative arachnoidal cleavage plane as well as the postoperative motor outcome.

Methods: Clinical data were retrospectively collected from surgical cases involving patients affected by convexity, parasagittal, or falx meningiomas involving the rolandic region, who received preoperative nTMS mapping of the motor cortex (M1) and nTMS-based diffusion tensor imaging (DTI) fiber tracking of the corticospinal tract before surgery at 2 different neurosurgical centers. Surgeons' self-reported evaluation of the impact of nTMS-based mapping on surgical strategy was analyzed. Moreover, the nTMS mapping accuracy was evaluated in comparison with intraoperative neurophysiological mapping (IONM). Lastly, we assessed the role of nTMS as well as other pre- and intraoperative parameters for predicting the patients' motor outcome and the presence or absence of an intraoperative arachnoidal cleavage plane.

Results: Forty-seven patients were included in this study. The nTMS-based planning was considered useful in 89.3% of cases, and a change of the surgical strategy was observed in 42.5% of cases. The agreement of nTMS-based planning and IONM-based strategy in 35 patients was 94.2%. A new permanent motor deficit occurred in 8.5% of cases (4 of 47). A higher resting motor threshold (RMT) and the lack of an intraoperative arachnoidal cleavage plane were the only independent predictors of a poor motor outcome (p = 0.04 and p = 0.02, respectively). Moreover, a higher RMT and perilesional edema also predicted the lack of an arachnoidal cleavage plane (p = 0.01 and p = 0.03, respectively). Preoperative motor status, T2 cleft sign, contrast-enhancement pattern, and tumor volume had no predictive value.

Conclusions: nTMS-based motor mapping is a useful tool for presurgical assessment of rolandic meningiomas, especially when a clear cleavage plane with M1 is not present. Moreover, the RMT can indicate the presence or absence of an intraoperative cleavage plane and predict the motor outcome, thereby helping to identify high-risk patients before surgery.
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http://dx.doi.org/10.3171/2019.3.JNS183411DOI Listing
June 2019

Surgery of malignant motor-eloquent gliomas guided by sodium-fluorescein and navigated transcranial magnetic stimulation: a novel technique to increase the maximal safe resection.

J Neurosurg Sci 2019 Dec 6;63(6):670-678. Epub 2019 May 6.

Division of Neurosurgery, BIOMORF Department, University of Messina, Messina, Italy.

Background: Maximal safe resection is the goal of modern surgical treatment of high-grade gliomas (HGGs) located close to the motor cortex (M1) and/or the corticospinal tract (CST). Preoperative planning based on navigated transcranial magnetic stimulation (nTMS) and fluorescence-guided resection (FGR) using sodium-fluorescein have been separately described to increase the extent of resection (EOR) while preserving the motor pathway. We assessed the efficacy of the combination of these techniques for surgery of motor-eloquent HGGs.

Methods: We enrolled patients with motor-eloquent HGGs operated at the Departments of Neurosurgery of the University of Messina, Italy, and of the Charitè Universitatsmedizin Berlin, Germany, between 2016 and 2019. All patients underwent nTMS mapping of M1, and nTMS-based DTI tractography of CST. Tumor resection was guided by intraoperative neurophysiological mapping (IONM) supported by sodium-fluorescein fluorescence and by intraoperative visualization of the nTMS-based information through neuronavigation. EOR and new permanent motor deficits were compared with a historical control group of patients operated exclusively with IONM guidance.

Results: Seventy-nine patients were enrolled, while 55 patients were included as controls. The gross total resection (GTR) rate was significantly higher in patients operated using nTMS + FGR compared with controls (64.5% vs. 47.2%, P=0.04). As well, postoperative new permanent motor deficits were reduced in the study group vs. controls (11.4% vs. 20%).

Conclusions: In this series, the combination of sodium-fluorescein FGR with nTMS-based planning improved surgical treatment of motor-eloquent HGGs. It represents a valuable support to IONM-guided resection, increasing the GTR rate while reducing the occurrence of permanent motor deficits.
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http://dx.doi.org/10.23736/S0390-5616.19.04710-6DOI Listing
December 2019

Manual for clinical language tractography.

Acta Neurochir (Wien) 2019 06 19;161(6):1125-1137. Epub 2019 Apr 19.

Department of Neurosurgery, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background: We introduce a user-friendly, standardized protocol for tractography of the major language fiber bundles.

Method: The introduced method uses dMRI images for tractography whereas the ROI definition is based on structural T1 MPRAGE MRI templates, without normalization to MNI space. ROIs for five language-relevant fiber bundles were visualized on an axial, coronal, or sagittal view of T1 MPRAGE images. The ROIs were defined based upon the tracts' obligatory pathways, derived from literature and own experiences in peritumoral tractography.

Results: The resulting guideline was evaluated for each fiber bundle in ten healthy subjects and ten patients by one expert and three raters. Overall, 300 ROIs were evaluated and compared. The targeted language fiber bundles could be tracked in 88% of the ROI pairs, based on the raters' result blinded ROI placements. The evaluation indicated that the precision of the ROIs did not relate to the varying experience of the raters.

Conclusions: Our guideline introduces a standardized language tractography method for routine preoperative workup and for research contexts. The ROI placement guideline based on easy-to-identify anatomical landmarks proved to be user-friendly and accurate, also in inexperienced test persons.
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http://dx.doi.org/10.1007/s00701-019-03899-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6525736PMC
June 2019
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