Transcranial transmission ultrasound for reliable non-invasive exclusion of intracranial hypertension in traumatic brain injury patients -A proof of concept study.

For many years, non-invasive methods to measure intracranial pressure (ICP) have been unsuccessful. However, such methods are crucial for the assessment of patients with non-penetrating traumatic brain injuries (TBI) who are unconscious. In this study, we explored the use of Transcranial Transmission Ultrasound (TTUS) to gather experimental data through brain pulsatility, assessing its effectiveness in detecting high ICP using machine learning analysis. We included patients with severe TBI under invasive ICP monitoring in our intensive care unit. During periods of both normal and elevated ICP, we simultaneously recorded ICP, arterial blood pressure, heart rate, and TTUS measurements. Our classification model was based on data from 9 patients, encompassing 387 instances of elevated ICP (>15 mmHg) and 345 instances of normal ICP (<10 mmHg), and validated through a leave-one-subject-out method. The study, conducted from October 2021 to October 2022, involved 25 patients with an average age of 61.6 ± 17.6 years, producing 279 data sets with an average ICP of 11.3 mmHg (1st quartile 6·1 mmHg; 3rd quartile 14·8 mmHg). The automated TTUS analysis effectively identified ICP values over 15 mmHg with a 100% sensitivity and 47% specificity. It achieved a 100% negative predictive value and a 14% positive predictive value. This suggests that TTUS can accurately rule out high ICP above 15 mmHg in TBI patients, indicating patients who may need immediate imaging or intervention. These promising results, if confirmed and expanded in larger studies, could lead to the first reliable, non-invasive screening tool for detecting elevated ICP.

Resolving spatial response heterogeneity in glioblastoma.

PURPOSE: Spatial intratumoral heterogeneity poses a significant challenge for accurate response assessment in glioblastoma. Multimodal imaging coupled with advanced image analysis has the potential to unravel this response heterogeneity. METHODS: Based on automated tumor segmentation and longitudinal registration with follow-up imaging, we categorized contrast-enhancing voxels of 61 patients with suspected recurrence of glioblastoma into either true tumor progression (TP) or pseudoprogression (PsP). To allow the unbiased analysis of semantically related image regions, adjacent voxels with similar values of cerebral blood volume (CBV), FET-PET, and contrast-enhanced T1w were automatically grouped into supervoxels. We then extracted first-order statistics as well as texture features from each supervoxel. With these features, a Random Forest classifier was trained and validated employing a 10-fold cross-validation scheme. For model evaluation, the area under the receiver operating curve, as well as classification performance metrics were calculated. RESULTS: Our image analysis pipeline enabled reliable spatial assessment of tumor response. The predictive model reached an accuracy of 80.0% and a macro-weighted AUC of 0.875, which takes class imbalance into account, in the hold-out samples from cross-validation on supervoxel level. Analysis of feature importances confirmed the significant role of FET-PET-derived features. Accordingly, TP- and PsP-labeled supervoxels differed significantly in their 10th and 90th percentile, as well as the median of tumor-to-background normalized FET-PET. However, CBV- and T1c-related features also relevantly contributed to the model's performance. CONCLUSION: Disentangling the intratumoral heterogeneity in glioblastoma holds immense promise for advancing precise local response evaluation and thereby also informing more personalized and localized treatment strategies in the future.

High Prevalence and Clinical Relevance of Intrapulmonary Vascular Dilatations in Patients Undergoing TIPS Implantation.

BACKGROUND & AIMS: Considerate patient selection is vital to ensure the best possible outcomes after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, data regarding the impact of intrapulmonary vascular dilatations (IPVDs) or hepatopulmonary syndrome (HPS) on the clinical course after TIPS implantation is lacking. Hence, this study aimed to investigate the relevance of IPVD and HPS in patients undergoing TIPS implantation. METHODS: Contrast enhanced echocardiography and blood gas analysis were utilized to determine presence of IPVD and HPS. Multivariable competing risk analyses were performed to evaluate cardiac decompensation (CD), hepatic decompensation (HD), and liver transplant (LTx)-free survival within 1 year of follow-up. RESULTS: Overall, 265 patients were included, of whom 136 had IPVD and 71 fulfilled the HPS criteria. Patients with IPVD had lower Freiburg index of post-TIPS survival (FIPS) scores, lower creatinine, and more often received TIPS because of variceal bleeding. Presence of IPVD was associated with a significantly higher incidence of CD (hazard ratio [HR], 1.756; 95% confidence interval [CI], 1.011-3.048; P = .046) and HD (HR, 1.841; 95% CI, 1.255-2.701; P = .002). However, LTx-free survival was comparable between patients with and without IPVD (HR, 1.081; 95% CI, 0.630-1.855; P = .780). Patients with HPS displayed a trend towards more CD (HR, 1.708; 95% CI, 0.935-3.122; P = .082) and HD (HR, 1.458; 95% CI, 0.934-2.275; P = .097) that failed to reach statistical significance. LTx-free survival did not differ in those with HPS compared with patients without HPS, respectively (HR, 1.052; 95% CI, 0.577-1.921; P = .870). CONCLUSION: Screening for IPVD before TIPS implantation could help to further identify patients at higher risk of CD and HD.

Sex-dependent characteristics and outcomes after clipping of unruptured intracranial aneurysms: a multicenter propensity score-matched study.

OBJECTIVE: Disparities in the epidemiology and growth rates of aneurysms between the sexes are known. However, little is known about sex-dependent outcomes after microsurgical clipping of unruptured intracranial aneurysms (UIAs). The aim of this study was to examine sex differences in characteristics and outcomes after microsurgical clipping of UIAs and to perform a propensity score-matched analysis using an international multicenter cohort. METHODS: This retrospective cohort study involved the participation of 15 centers spanning four continents. It included adult patients who underwent clipping of UIAs between January 2016 and December 2020. Patients were stratified according to their sex and analyzed for differences in morbidities and aneurysm characteristics. Based on this stratification, female patients were matched to male patients in a 1:1 ratio with a caliper width of 0.1 using propensity score matching. Endpoints included postoperative complications, neurological performance, and aneurysm occlusion at discharge and 24 months after clip placement. RESULTS: A total of 2245 patients with a mean age of 57.3 (range 20-87) years were included. Of these patients, 1675 (74.6%) were female. Female patients were significantly older (mean 57.6 vs 56.4 years, p = 0.03) but had fewer comorbidities. Aneurysms of the internal carotid artery (7.1% vs 4.2%), posterior communicating artery (6.9% vs 1.9%), and ophthalmic artery (6.0% vs 2.8%) were more commonly treated surgically in females, while clipping of aneurysms of the anterior communicating artery was more frequent in males (17.0% vs 25.3%; all p < 0.001). After propensity score matching, female patients were found to have had significantly fewer pulmonary complications (1.4% vs 4.2%, p = 0.01). However, general morbidity (24.5% vs 25.2%, p = 0.72) and mortality (0.5% vs 1.1%, p = 0.34), as well as neurological performance (p = 0.58), were comparable at discharge in both sexes. Lastly, rates of aneurysm occlusion at the time of discharge (95.5% vs 94.9%, p = 0.71) and 24 months after surgery (93.8% vs 96.1%, p = 0.22) did not significantly differ between male and female patients. CONCLUSIONS: Despite overall differences between male and female patients in demographics, comorbidities, and treated aneurysm location, sex did not relevantly affect surgical performance or perioperative complication rates.

Quantitative Assessment of Tumor Contact with Neurogenic Zones and Its Effects on Survival: Insights beyond Traditional Predictors.

So far, the cellular origin of glioblastoma (GBM) needs to be determined, with prevalent theories suggesting emergence from transformed endogenous stem cells. Adult neurogenesis primarily occurs in two brain regions: the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus. Whether the proximity of GBM to these neurogenic niches affects patient outcome remains uncertain. Previous studies often rely on subjective assessments, limiting the reliability of those results. In this study, we assessed the impact of GBM's relationship with the cortex, SVZ and SGZ on clinical variables using fully automated segmentation methods. In 177 glioblastoma patients, we calculated optimal cutpoints of minimal distances to the SVZ and SGZ to distinguish poor from favorable survival. The impact of tumor contact with neurogenic zones on clinical parameters, such as overall survival, multifocality, MGMT promotor methylation, Ki-67 and KPS score was also examined by multivariable regression analysis, chi-square test and Mann-Whitney-U. The analysis confirmed shorter survival in tumors contacting the SVZ with an optimal cutpoint of 14 mm distance to the SVZ, separating poor from more favorable survival. In contrast, tumor contact with the SGZ did not negatively affect survival. We did not find significant correlations with multifocality or MGMT promotor methylation in tumors contacting the SVZ, as previous studies discussed. These findings suggest that the spatial relationship between GBM and neurogenic niches needs to be assessed differently. Objective measurements disprove prior assumptions, warranting further research on this topic.

Spinal Intradural Tumor Resection via Long-Segment Approaches and Clinical Long-Term Follow-Up.

INTRODUCTION: Spinal intradural tumors account for 15% of all CNS tumors. Typical tumor entities include ependymomas, astrocytomas, meningiomas, and neurinomas. In cases of multiple affected segments, extensive approaches may be necessary to achieve the gold standard of complete tumor resection. METHODS: We performed a bicentric, retrospective cohort study of all patients equal to or older than 14 years who underwent multi-segment surgical treatment for spinal intradural tumors between 2007 and 2023 with approaches longer than four segments without instrumentation. We assessed the surgical technique and the clinical outcome regarding signs of symptomatic spinal instability. Children were excluded from our cohort. RESULTS: In total, we analyzed 33 patients with a median age of 44 years and interquartile range IQR of 30-56 years, including the following tumors: 21 ependymomas, one subependymoma-ependymoma mixed tumor, two meningiomas, two astrocytomas, and seven patients with other entities. The median length of the approach was five spinal segments with a range of 4-14 and with the foremost localization in the cervical or thoracic spine. Laminoplasty was the most chosen approach (72.2%). The median time to follow-up was 13 months IQR (4-56 months). Comparing pre- and post-surgery outcomes, 72.2% of the patients (n = 24) reported pain improvement after surgery. The median modified McCormick scores pre- and post surgery were equal to II IQR (I-II) and II IQR (I-III), respectively. DISCUSSION: We achieved satisfying results with long-segment approaches. In general, patients reported pain improvement after surgery and received similar low modified McCormick scores pre- and post surgery and did not undergo secondary dorsal fixation. Thus, we conclude that intradural tumor resection via extensive approaches does not seem to impair long-term spinal stability in our cohort.

Toward a systematic grading for the selection of patients to undergo awake surgery: identifying suitable predictor variables.

Background: Awake craniotomy is the standard of care for treating language eloquent gliomas. However, depending on preoperative functionality, it is not feasible in each patient and selection criteria are highly heterogeneous. Thus, this study aimed to identify broadly applicable predictor variables allowing for a more systematic and objective patient selection. Methods: We performed post-hoc analyses of preoperative language status, patient and tumor characteristics including language eloquence of 96 glioma patients treated in a single neurosurgical center between 05/2018 and 01/2021. Multinomial logistic regression and stepwise variable selection were applied to identify significant predictors of awake surgery feasibility. Results: Stepwise backward selection confirmed that a higher number of paraphasias, lower age, and high language eloquence level were suitable indicators for an awake surgery in our cohort. Subsequent descriptive and ROC-analyses indicated a cut-off at ≤54 years and a language eloquence level of at least 6 for awake surgeries, which require further validation. A high language eloquence, lower age, preexisting semantic and phonological aphasic symptoms have shown to be suitable predictors. Conclusion: The combination of these factors may act as a basis for a systematic and standardized grading of patients' suitability for an awake craniotomy which is easily integrable into the preoperative workflow across neurosurgical centers.

Radiomics-based prediction of local control in patients with brain metastases following postoperative stereotactic radiotherapy.

BACKGROUND: Surgical resection is the standard of care for patients with large or symptomatic brain metastases (BMs). Despite improved local control after adjuvant stereotactic radiotherapy, the risk of local failure (LF) persists. Therefore, we aimed to develop and externally validate a pre-therapeutic radiomics-based prediction tool to identify patients at high LF risk. METHODS: Data were collected from A Multicenter Analysis of Stereotactic Radiotherapy to the Resection Cavity of Brain Metastases (AURORA) retrospective study (training cohort: 253 patients from two centers; external test cohort: 99 patients from five centers). Radiomic features were extracted from the contrast-enhancing BM (T1-CE MRI sequence) and the surrounding edema (FLAIR sequence). Different combinations of radiomic and clinical features were compared. The final models were trained on the entire training cohort with the best parameter set previously determined by internal 5-fold cross-validation and tested on the external test set. RESULTS: The best performance in the external test was achieved by an elastic net regression model trained with a combination of radiomic and clinical features with a concordance index (CI) of 0.77, outperforming any clinical model (best CI: 0.70). The model effectively stratified patients by LF risk in a Kaplan-Meier analysis (p < 0.001) and demonstrated an incremental net clinical benefit. At 24 months, we found LF in 9% and 74% of the low and high-risk groups, respectively. CONCLUSIONS: A combination of clinical and radiomic features predicted freedom from LF better than any clinical feature set alone. Patients at high risk for LF may benefit from stricter follow-up routines or intensified therapy.

New Breakthroughs in the Diagnosis of Leptomeningeal Carcinomatosis: A Review of Liquid Biopsies of Cerebrospinal Fluid.

Leptomeningeal carcinomatosis represents a terminal stage and is a devastating complication of cancer. Despite its high incidence, current diagnostic methods fail to accurately detect this condition in a timely manner. This failure to diagnose leads to the refusal of treatment and the absence of clinical trials, hampering the development of new therapy strategies. The use of liquid biopsy is revolutionizing the field of diagnostic oncology. The dynamic and non-invasive detection of tumor markers has enormous potential in cancer diagnostics and treatment. Leptomeningeal carcinomatosis is a condition where invasive tissue biopsy is not part of the routine diagnostic analysis, making liquid biopsy an essential diagnostic tool. Several elements in cerebrospinal fluid (CSF) have been investigated as potential targets of liquid biopsy, including free circulating tumor cells, free circulating nucleic acids, proteins, exosomes, and even non-tumor cells as part of the dynamic tumor microenvironment. This review aims to summarize current breakthroughs in the research on liquid biopsy, including the latest breakthroughs in the identification of tumor cells and nucleic acids, and give an overview of future directions in the diagnosis of leptomeningeal carcinomatosis.

Single brain metastases - prognostic factors and impact of residual tumor burden on overall survival.

Background: Brain metastases (BM) are a common and challenging issue, with their incidence on the rise due to advancements in systemic therapies and increased patient survival. Most patients present with single BM, some of them without any further extracranial metastasis (i.e., solitary BM). The significance of postoperative intracranial tumor volume in the treatment of singular and solitary BM is still debated. Objective: This study aimed to determine the impact of resection and postoperative tumor burden on overall survival (OS) in patients with single BM. Methods: Patients with surgically treated single BM between 04/2007-01/2020 were retrospectively included. Residual tumor burden (RTB) was determined by manual segmentation of early postoperative brain MRI (72 h). Survival analyses were performed using Kaplan-Meier estimates for univariate analysis and Cox regression proportional hazards model for multivariate analysis, using preoperative Karnofsky performance status scale (KPSS), age, sex, RTB, incomplete resection and singular/solitary BM as covariates. Results: 340 patients were included, median age 64 years (54-71). 119 patients (35%) had solitary BM, 221 (65%) singular BM. Complete resection (RTB=0) was achieved in 73%, median preoperative tumor burden was 11.2 cm3 (5-25), and RTB 0 cm3 (0-0.2). Median OS of patients with singular BM was 13 months (4-33) vs 20 months (5-92) for solitary BM; p=0.062. Multivariate analysis revealed singular BM as independent risk factor for poorer OS: HR 1.840 (1.202-2.817), p=0.005. Complete vs. incomplete resection showed no significant OS difference (13 vs. 13 months, p=0.737). When focusing on solitary BM, complete resection led to a longer OS than incomplete resection (21 vs. 8 months), without statistical significance(p=0.250). Achieving RTB=0 resulted in higher OS for patients with solitary BM compared to singular BM (21 vs. 12 months, p=0.027). Patients who received postoperative radiotherapy (RT) had significantly longer OS compared to those without it (14 vs. 4 months, p<0.001), with favorable OS in those receiving stereotactic radiosurgery (SRS) (15 months (3-42), p<0.001) or hypofractionated stereotactic radiotherapy (HSRT). Conclusion: When complete intracranial tumor resection RTB=0 is achieved, patients with solitary BM have a favorable outcome compared to singular BM. Singular BM was confirmed as independent risk factor. There is a strong presumption that complete resection leads to an improved oncological prognosis. Patients with solitary BM tend to benefit with a favorable outcome following complete resection. Hence, surgical resection should be considered as a treatment option for patients presenting with either no or minimal extracranial disease. Furthermore, the highly favorable impact of postoperative RT on OS was demonstrated and confirmed, especially with SRS or HSRT.

Function-guided differences of arcuate fascicle and inferior fronto-occipital fascicle tractography as diagnostic indicators for surgical risk stratification.

BACKGROUND: Several patients with language-eloquent gliomas face language deterioration postoperatively. Persistent aphasia is frequently associated with damage to subcortical language pathways. Underlying mechanisms still need to be better understood, complicating preoperative risk assessment. This study compared qualitative and quantitative functionally relevant subcortical differences pre- and directly postoperatively in glioma patients with and without aphasia. METHODS: Language-relevant cortical sites were defined using navigated transcranial magnetic stimulation (nTMS) language mapping in 74 patients between 07/2016 and 07/2019. Post-hoc nTMS-based diffusion tensor imaging tractography was used to compare a tract's pre- and postoperative visualization, volume and fractional anisotropy (FA), and the preoperative distance between tract and lesion and postoperative overlap with the resection cavity between the following groups: no aphasia (NoA), tumor- or previous resection induced aphasia persistent pre- and postoperatively (TIA_P), and surgery-induced transient or permanent aphasia (SIA_T or SIA_P). RESULTS: Patients with NoA, TIA_P, SIA_T, and SIA_P showed distinct fasciculus arcuatus (AF) and inferior-fronto-occipital fasciculus (IFOF) properties. The AF was more frequently reconstructable, and the FA of IFOF was higher in NoA than TIA_P cases (all p ≤ 0.03). Simultaneously, SIA_T cases showed higher IFOF fractional anisotropy than TIA_P cases (p < 0.001) and the most considerable AF volume loss overall. While not statistically significant, the four SIA_P cases showed complete loss of ventral language streams postoperatively, the highest resection-cavity-AF-overlap, and the shortest AF to tumor distance. CONCLUSION: Functionally relevant qualitative and quantitative differences in AF and IFOF provide a pre- and postoperative pathophysiological and clinically relevant diagnostic indicator that supports surgical risk stratification.

Noninvasive- and invasive mapping reveals similar language network centralities - A function-based connectome analysis.

BACKGROUND: Former comparisons between direct cortical stimulation (DCS) and navigated transcranial magnetic stimulation (nTMS) only focused on cortical mapping. While both can be combined with diffusion tensor imaging, their differences in the visualization of subcortical and even network levels remain unclear. Network centrality is an essential parameter in network analysis to measure the importance of nodes identified by mapping. Those include Degree centrality, Eigenvector centrality, Closeness centrality, Betweenness centrality, and PageRank centrality. While DCS and nTMS have repeatedly been compared on the cortical level, the underlying network identified by both has not been investigated yet. METHOD: 27 patients with brain lesions necessitating preoperative nTMS and intraoperative DCS language mapping during awake craniotomy were enrolled. Function-based connectome analysis was performed based on the cortical nodes obtained through the two mapping methods, and language-related network centralities were compared. RESULTS: Compared with DCS language mapping, the positive predictive value of cortical nTMS language mapping is 74.1%, with good consistency of tractography for the arcuate fascicle and superior longitudinal fascicle. Moreover, network centralities did not differ between the two mapping methods. However, ventral stream tracts can be better traced based on nTMS mappings, demonstrating its strengths in acquiring language-related networks. In addition, it showed lower centralities than other brain areas, with decentralization as an indicator of language function loss. CONCLUSION: This study deepens the understanding of language-related functional anatomy and proves that non-invasive mapping-based network analysis is comparable to the language network identified via invasive cortical mapping.

Adjuvant re-irradiation vs. no early re-irradiation of resected recurrent glioblastoma: pooled comparative cohort analysis from two tertiary centers.

BACKGROUND: The optimal management strategy for recurrent glioblastoma (rGBM) remains uncertain, and the impact of re-irradiation (Re-RT) on overall survival (OS) is still a matter of debate. This study included patients who achieved gross total resection (GTR) after a second surgery after recurrence, following the GlioCave criteria. METHODS: Inclusion criteria include being 18 years or older, having histologically confirmed locally recurrent IDHwt or IDH unknown GBM, achieving MRI-proven GTR after the second surgery, having a Karnofsky performance status of at least 60% after the second surgery, having a minimum interval of 6 months between the first radiotherapy and the second surgery, and a maximum of 8 weeks from second surgery to the start of Re-RT. RESULTS: A total of 44 patients have met the inclusion criteria. The median OS after the second surgery was 14 months. All patients underwent standard treatment after initial diagnosis, including maximum safe resection, adjuvant radiochemotherapy and adjuvant chemotherapy. Re-RT did not significantly impact OS. However, MGMT promoter methylation status and a longer interval (> 12 months) between treatments were associated with better OS. Multivariate analysis revealed the MGMT status as the only significant predictor of OS. CONCLUSION: Factors such as MGMT promoter methylation status and treatment interval play crucial roles in determining patient outcomes after second surgery. Personalized treatment strategies should consider these factors to optimize the management of rGBM. Prospective research is needed to define the value of re-RT after second surgery and to inform decision making in this situation.

Image Quality and Radiation Exposure in Abdominal Angiography: A Head-to-Head Comparison of Conventional Detector-Dose-Driven Versus Contrast-to-Noise Ratio-Driven Exposure Control at Various Source-to-Image Receptor Distances and Collimations in a Pilot Phantom and Animal Study.

OBJECTIVES: This phantom and animal pilot study aimed to compare image quality and radiation exposure between detector-dose-driven exposure control (DEC) and contrast-to-noise ratio (CNR)-driven exposure control (CEC) as functions of source-to-image receptor distance (SID) and collimation. MATERIALS AND METHODS: First, an iron foil simulated a guide wire in a stack of polymethyl methacrylate and aluminum plates representing patient thicknesses of 15, 25, and 35 cm. Fluoroscopic images were acquired using 5 SIDs ranging from 100 to 130 cm and 2 collimations (full field of view, collimated field of view: 6 × 6 cm). The iron foil CNRs were calculated, and radiation doses in terms of air kerma rate were obtained and assessed using a multivariate regression. Second, 5 angiographic scenarios were created in 2 anesthetized pigs. Fluoroscopic images were acquired at 2 SIDs (110 and 130 cm) and both collimations. Two blinded experienced readers compared image quality to the reference image using full field of view at an SID of 110 cm. Air kerma rate was obtained and compared using t tests. RESULTS: Using DEC, both CNR and air kerma rate increased significantly at longer SID and collimation below the air kerma rate limit. When using CEC, CNR was significantly less dependent of SID, collimation, and patient thickness. Air kerma rate decreased at longer SID and tighter collimation. After reaching the air kerma rate limit, CEC behaved similarly to DEC. In the animal study using DEC, image quality and air kerma rate increased with longer SID and collimation (P < 0.005). Using CEC, image quality was not significantly different than using longer SID or tighter collimation. Air kerma rate was not significantly different at longer SID but lower using collimation (P = 0.012). CONCLUSIONS: CEC maintains the image quality with varying SID and collimation stricter than DEC, does not increase the air kerma rate at longer SID and reduces it with tighter collimation. After reaching the air kerma rate limit, CEC and DEC perform similarly.

Permanent deterioration of fine motor skills after the resection of tumors in the supplementary motor area.

Supplementary motor area syndrome (SMAS) represents a common neurosurgical sequela. The incidence and time frame of its occurrence have yet to be characterized after surgery for brain tumors. We examined patients suffering from a brain tumor preoperatively, postoperatively, and during follow-up examinations after three months, including fine motor skills testing and transcranial magnetic stimulation (TMS). 13 patients suffering from a tumor in the dorsal part of the superior frontal gyrus underwent preoperative, early postoperative, and 3-month follow-up testing of fine motor skills using the Jebsen-Taylor Hand Function Test (JHFT) and the Nine-Hole Peg Test (NHPT) consisting of 8 subtests for both upper extremities. They completed TMS for cortical motor function mapping. Test completion times (TCTs) were recorded and compared. No patient suffered from neurological deficits before surgery. On postoperative day one, we detected motor deficits in two patients, which remained clinically stable at a 3-month follow-up. Except for page-turning, every subtest indicated a significant worsening of function, reflected by longer TCTs (p < 0.05) in the postoperative examinations for the contralateral upper extremity (contralateral to the tumor manifestation). At 3-month follow-up examinations for the contralateral upper extremity, each subtest indicated significant worsening compared to the preoperative status despite improvement to the immediate postoperative level. We also detected significantly longer TCTs (p < 0.05) postoperatively in the ipsilateral upper extremity. This study suggests a long-term worsening of fine motor skills even three months after SMA tumor resection, indicating the necessity of targeted physical therapy for these patients.

Motor mapping of the hand muscles using peripheral innervation-based navigated transcranial magnetic stimulation to identify functional reorganization of primary motor regions in malignant tumors.

Tumor-related motor reorganization remains unclear. Navigated transcranial magnetic stimulation (nTMS) can investigate plasticity non-invasively. nTMS-induced motor-evoked potentials (MEPs) of different muscles are commonly used to measure the center of gravity (CoG), the location with the highest density of corticospinal neurons in the precentral gyrus. We hypothesized that a peripheral innervation-based MEP analysis could outline the tumor-induced motor reorganization with a higher clinical and oncological relevance. Then, 21 patients harboring tumors inside the left corticospinal tract (CST) or precentral gyrus were enrolled in group one (G1), and 24 patients with tumors outside the left CST or precentral gyrus were enrolled in Group 2 (G2). Median- and ulnar-nerve-based MEP analysis combined with diffusion tensor imaging fiber tracking was used to explore motor function distribution. There was no significant difference in CoGs or size of motor regions and underlying tracts between G1 and G2. However, G1 involved a sparser distribution of motor regions and more motor-positive sites in the supramarginal gyrus-tumors inside motor areas induced motor reorganization. We propose an "anchor-and-ship theory" hypothesis for this process of motor reorganization: motor CoGs are stably located in the cortical projection area of the CST, like a seated anchor, as the core area for motor output. Primary motor regions can relocate to nearby gyri via synaptic plasticity and association fibers, like a ship moving around its anchor. This principle can anticipate functional reorganization and be used as a neuro-oncological tool for local therapy, such as radiotherapy or surgery.

Impact of function-guided glioma treatment on oncological outcome in the elderly.

Introduction: Many patients with high-grade gliomas (HGG) are of older age. Research question: We hypothesize that pre- and intraoperative mapping and monitoring preserve functional status in elderly patients while gross total resection (GTR) is the aim, resulting in overall survival (OS) rates comparable to the general population with HGG. Material and methods: We subdivided a prospective cohort of 168 patients above 65 years with eloquent high-grade gliomas into four groups ([years/cases] 1: 65-69/58; 2: 70-74/47; 3: 75-79/43; 4: >79/20). All patients underwent preoperative noninvasive mapping, which was also used for decision-making, intraoperative neuromonitoring in 138 cases, direct cortical and/or subcortical motor mapping in 66 and 50 cases, and awake language mapping in 11 cases. Results: GTR and subtotal resection (STR) could be achieved in 65% and 28%, respectively. Stereotactic biopsy was performed in 8% of cases. Postoperatively, we found transient and permanent functional deficits in 13% and 11% of cases. Postoperative Karnofsky Performance Scale (KPS) did not differ between subgroups. Patients with long-term follow-up (51%) had a progression-free survival of 5.5 (1-47) months and an overall survival of 10.5 (0-86) months. Discussion and conclusion: The interdisciplinary glioma treatment in the elderly is less age-dependent but must be adjusted to the functional status. Function-guided surgical resections could be performed as usual, with maximal tumor resection being the primary goal. However, less network capacity in the elderly to compensate for deficits might cause higher rates of permanent deficits in this group of patients with more fast-growing malignant gliomas.

Treatment outcome of IDH1/2 wildtype CNS WHO grade 4 glioma histologically diagnosed as WHO grade II or III astrocytomas.

BACKGROUND: Isocitrate dehydrogenase (IDH)1/2 wildtype (wt) astrocytomas formerly classified as WHO grade II or III have significantly shorter PFS and OS than IDH mutated WHO grade 2 and 3 gliomas leading to a classification as CNS WHO grade 4. It is the aim of this study to evaluate differences in the treatment-related clinical course of these tumors as they are largely unknown. METHODS: Patients undergoing surgery (between 2016-2019 in six neurosurgical departments) for a histologically diagnosed WHO grade 2-3 IDH1/2-wt astrocytoma were retrospectively reviewed to assess progression free survival (PFS), overall survival (OS), and prognostic factors. RESULTS: This multi-center study included 157 patients (mean age 58 years (20-87 years); with 36.9% females). The predominant histology was anaplastic astrocytoma WHO grade 3 (78.3%), followed by diffuse astrocytoma WHO grade 2 (21.7%). Gross total resection (GTR) was achieved in 37.6%, subtotal resection (STR) in 28.7%, and biopsy was performed in 33.8%. The median PFS (12.5 months) and OS (27.0 months) did not differ between WHO grades. Both, GTR and STR significantly increased PFS (P < 0.01) and OS (P < 0.001) compared to biopsy. Treatment according to Stupp protocol was not associated with longer OS or PFS compared to chemotherapy or radiotherapy alone. EGFR amplification (P = 0.014) and TERT-promotor mutation (P = 0.042) were associated with shortened OS. MGMT-promoter methylation had no influence on treatment response. CONCLUSIONS: WHO grade 2 and 3 IDH1/2 wt astrocytomas, treated according to the same treatment protocols, have a similar OS. Age, extent of resection, and strong EGFR expression were the most important treatment related prognostic factors.

Cortical stimulation depth of nTMS investigated in a cohort of convexity meningiomas above the primary motor cortex.

BACKGROUND: In clinical routine, navigated transcranial magnetic stimulation (nTMS) is usually applied down to 25 mm. Yet, besides clinical experience and mathematical models, the penetration depth remains unclear. This study aims to investigate the maximum cortical stimulation depth of nTMS in patients with meningioma above the primary motor cortex, causing a displacement of the primary motor cortex away from the skull. NEW METHOD: nTMS stimulation data was reviewed regarding the maximum depth of stimulations eliciting motor-evoked potentials (MEPs). Additionally, electric field values and stimulation intensity were analyzed. RESULTS: Out of a consecutive cohort of 17 meningioma cases, 3 cases of meningioma located in motor-eloquent regions of the upper extremity and 3 cases of the lower extremity were analyzed after fulfilling all inclusion criteria. Regarding the upper extremity motor representations, the MEP could be elicited at a stimulation depth of up to 44 mm, with an electric field of 69 V/m. These results were found in 1 case with the maximum potential distance to the cortex being higher than the maximum stimulation depth eliciting MEPs. For the lower extremities, a maximum depth of 40 mm was recorded (electric field 64 V/m). COMPARISON WITH EXISTING METHODS: None available CONCLUSIONS: The effect of nTMS is not limited to superficial cortical stimulation alone. Depending on electric-field intensity and focality, nTMS stimulation can be applied at a depth of 44 mm. In all cases, electric field strength was comparable and no superficial cortex with comparable electric field strength was observed to elicit MEPs.

The role of molecular tumor boards in neuro-oncology: a nationwide survey.

BACKGROUND: In neuro-oncology, the inclusion of tumor patients in the molecular tumor board has only become increasingly widespread in recent years, but so far there are no standards for indication, procedure, evaluation, therapy recommendations and therapy implementation of neuro-oncological patients. The present work examines the current handling of neuro-oncological patients included in molecular tumor boards in Germany. METHODS: We created an online based survey with questions covering the handling of neuro-oncologic patient inclusion, annotation of genetic analyses, management of target therapies and the general role of molecular tumor boards in neuro-oncology in Germany. We contacted all members of the Neuro-Oncology working group (NOA) of the German Cancer Society (DKG) by e-mail. RESULTS: 38 responses were collected. The majority of those who responded were specialists in neurosurgery or neurology with more than 10 years of professional experience working at a university hospital. Molecular tumor boards (MTB) regularly take place once a week and all treatment disciplines of neuro-oncology patients take part. The inclusions to the MTB are according to distinct tumors and predominantly in case of tumor recurrence. An independently MTB member mostly create the recommendations, which are regularly implemented in the tumor treatment. Recommendations are given for alteration classes 4 and 5. Problems exist mostly within the cost takeover of experimental therapies. The experimental therapies are mostly given in the department of medical oncology. CONCLUSIONS: Molecular tumor boards for neuro-oncological patients, by now, are not standardized in Germany. Similarities exists for patient inclusion and interpretation of molecular alterations; the time point of inclusion and implementation during the patient treatment differ between the various hospitals. Further studies for standardization and harmonisation are needed. In summary, most of the interviewees envision great opportunities and possibilities for molecular-based neuro-oncological therapy in the future.