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Objective: To compare the effects of different surgical approaches for selective amygdalohippocampectomy in patients with pharmacoresistant mesial temporal lobe epilepsy with regard to the neuropsychological outcome and to replicate an earlier study employing a matched-pair design.Method: 47 patients were randomised to subtemporal versus transsylvian approaches. Memory, language, attentional and executive functions were assessed before and 1 year after surgery. Multivariate analyses of variance (MANOVAs) with presurgical and postsurgical assessments as within-subject variables and approach and side of surgery as between-subject factors were calculated. Additionally, the frequencies of individual performance changes based on reliable change indices were analysed.Results: Seizure freedom International League Against Epilepsy (ILAE) 1a, was achieved in 62% of all patients without group difference. MANOVAs revealed no significant effects of approach on cognition. Tested separately for each parameter, verbal recognition memory declined irrespective of approach. Post hoc tests revealed that on group level, the subtemporal approach was associated with a worse outcome for verbal learning and delayed free recall as well as for semantic fluency. Accordingly, on individual level, more patients in the subtemporal group declined in verbal learning. Left side of surgery was associated with decline in naming regardless of approach.Conclusion: The main analysis did not confirm the effects of approach on memory outcome seen in our previous study. Post hoc testing, however, showed greater memory losses with the subtemporal approach. Previous findings were replicated for semantic fluency. The discrepant results are discussed on the background of the different study designs. [ABSTRACT FROM AUTHOR]

Background: Selective amygdalohippocampectomy is an effective treatment option for mesial temporal lobe epilepsy associated with hippocampal sclerosis.Methods: To describe and emphasize potential pitfalls during selective amygdalohippocampectomy via a modified navigated temporobasal approach, in cases, where temporal basal veins hinder the required elevation of the temporal lobe.Conclusions: Selective amygdalohippocampectomy via navigated temporobasal approach is a safe procedure that can reduce the rate of visual field deficits by avoiding damage of optic radiation. The option of a small subpial corticotomy of the inferior temporal gyrus allows sufficient elevation of the temporal lobe in cases with difficult basal venous anatomy. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to evaluate whether patients with drug-resistant mesial temporal lobe epilepsy (TLE) due to hippocampal 'gliosis only' have different MRI features than those with hippocampal sclerosis (HS). Most TLE patients have HS corresponding to severe neuronal loss and gliosis, but a few have 'gliosis only' without significant reduction of neuronal density. Methods: We analyzed the morphology of cerebral 3 T MRIs (T1, T2, and FLAIR) of 103 patients with HS and 20 with 'gliosis only' concerning hippocampal and amygdala aspect, volumes, and signal intensity (SI) using Fisher's exact test, Student's t test, and principal component analysis. Results: Visually, the ipsilateral hippocampus was hyperintense in both groups, but SI was markedly increased in 74% of HS and in 25% of 'gliosis only' patients; the ipsilateral hippocampus was smaller in 92% of HS and in 50% of 'gliosis only' patients, and its internal architecture was lost in 57% of HS and 5% of 'gliosis only' patients; the contralateral hippocampal SI was altered in 25% of HS and in 70% of 'gliosis only' patients (all p < 0.001). Ipsilateral hippocampus of HS patients had lower volume (mean ± SD 2.86 ± 0.87 ml) compared with that of 'gliosis only' patients (3.4 ± 1.02 ml) and had higher SI than the contralateral hippocampus of HS patients and then the hippocampus of 'gliosis only' patients (all p < 0.01). Conclusion: 'Gliosis only' has different MRI hippocampal characteristics than HS: less volume loss, less increase of the T2-w signal intensity, preservation of internal architecture, and more contralateral affection. [ABSTRACT FROM AUTHOR]

Although atypical meningioma recurs frequently in spite of total resection and/or radiotherapy, no consensus on optimal adjuvant management was found. However, several retrospective studies analysed the additional effect of adjuvant radiotherapy in atypical meningioma with inconsistent results. Therefrom, the purpose of this study was to evaluate prognostic factors influencing the recurrence/progression and progression-free survival (PFS) rates of atypical meningioma, particularly focused on the role of postoperative adjuvant radiotherapy. Between February 2001 and March 2015, 161 atypical meningioma resections were performed in our Department of Neurosurgery, of which, 128 cases underwent surgical treatment alone and 33 cases underwent surgery and radiotherapy. Kaplan-Meier analysis was used to provide median point estimates and PFS rates. The Cox-regression model was used in the univariate and multivariate analysis to identify significant factors associated with treatment. The extent of resection (Simpson grade I and II) significantly influenced the risk of recurrence (hazard ratio = 1.8, CI (95%) 1.3-2.6, p-value = 0.0004). There was no significant benefit for progression-free survival after adjuvant radiotherapy (hazard ratio = 1.48, CI (95%) 0.76-2.86, p-value = 0.22). Additionally, meningioma located at the anterior and posterior fossa showed a significantly longer PFS compared to other locations (p-value = 0.03). Adjuvant postoperative radiotherapy had no significant impact on recurrence/progression rate or PFS. The extent of resection according to Simpson grade remains the most important prognostic factor associated with lower recurrence/progression rates and longer PFS in patients with atypical meningioma. The location of the tumours at the anterior or posterior fossa was an independent factor associated with improved PFS. [ABSTRACT FROM AUTHOR]

Nonmalignant meningioma (NM) is the most common brain tumor in the United States (U.S.), accounting for 54% of nonmalignant brain tumors. This study aims to investigate the causes of death in NM patients and their possible associations with demographic factors. Using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed 116,430 NM patients diagnosed between the years 2004 and 2018. A total of 31,640 deaths were observed. Non-tumor diseases accounted for 63.9% of all deaths. Out of these non-tumor deaths, we found that the most common causes were heart disease (18.7% of deaths), cerebrovascular disease (7.4% of deaths), and Alzheimer disease (4.5% of deaths). On the other hand, cancer was responsible for 27.4% of deaths, while in situ and benign tumor deaths accounted for only 8.7%. This is the first U.S. population-based study to investigate the causes of death in NM patients. We found that non-tumor diseases accounted for the majority of deaths. The risks of mortality caused by heart disease, cerebrovascular disease, diabetes, and Alzheimer disease were significantly elevated. These data can help improve survival outcomes for NM patients, particularly if adjusted by demographic risk factors. [ABSTRACT FROM AUTHOR]

The pathophysiology of degenerative cervical myelopathy (DCM) is characterized by chronic compression-induced damage to the spinal cord leading to secondary harm such as disruption of the blood spinal cord barrier (BSCB). It is therefore the purpose of this study to analyze BSCB disruption in pre- and postoperative DCM patients and to correlate those with the clinical status and postoperative outcome. This prospectively controlled cohort included 50 DCM patients (21 female; 29 male; mean age: 62.9 ± 11.2 years). As neurological healthy controls, 52 (17 female; 35 male; mean age 61.8 ± 17.3 years) patients with thoracic abdominal aortic aneurysm (TAAA) and indication for open surgery were included. All patients underwent a neurological examination and DCM-associated scores (Neck Disability Index, modified Japanese Orthopaedic Association Score) were assessed. To evaluate the BSCB status, blood and cerebrospinal fluid (CSF) samples (lumbar puncture or CSF drainage) were taken preoperatively and in 15 DCM patients postoperatively (4 female; 11 male; mean age: 64.7 ± 11.1 years). Regarding BSCB disruption, CSF and blood serum were examined for albumin, immunoglobulin (Ig) G, IgA and IgM. Quotients for CSF/serum were standardized and calculated according to Reiber diagnostic criteria. Significantly increased preoperative CSF/serum quotients were found in DCM patients as compared to control patients: AlbuminQ (p <.001), IgAQ (p <.001) and IgGQ (p <.001). IgMQ showed no significant difference (T = − 1.15, p =.255). After surgical decompression, neurological symptoms improved in DCM patients, as shown by a significantly higher postoperative mJOA compared to the preoperative score (p =.001). This neurological improvement was accompanied by a significant change in postoperative CSF/serum quotients for Albumin (p =.005) and IgG (p =.004) with a trend of a weak correlation between CSF markers and neurological recovery. This study further substantiates the previous findings, that a BSCB disruption in DCM patients is evident. Interestingly, surgical decompression appears to be accompanied by neurological improvement and a reduction of CSF/serum quotients, implying a BSCB recovery. We found a weak association between BSCB recovery and neurological improvement. A BSCB disruption might be a key pathomechanism in DCM patients, which could be relevant to treatment and clinical recovery. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma is the most frequent and malignant primary brain tumor. Even in the subgroup with O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and favorable response to first-line therapy, survival after relapse is short (12 months). Standard therapy for recurrent MGMT-methylated glioblastoma is not standardized and may consist of re-resection, re-irradiation, and chemotherapy with temozolomide (TMZ), lomustine (CCNU), or a combination thereof. Preclinical results show that meclofenamate (MFA), originally developed as a nonsteroidal anti-inflammatory drug (NSAID) and registered in the USA, sensitizes glioblastoma cells to temozolomide-induced toxicity via inhibition of gap junction-mediated intercellular cytosolic traffic and demolishment of tumor microtube (TM)-based network morphology. Methods: In this study, combined MFA/TMZ therapy will be administered (orally) in patients with first relapse of MGMT-methylated glioblastoma. A phase I component (6–12 patients, 2 dose levels of MFA + standard dose TMZ) evaluates safety and feasibility and determines the dose for the randomized phase II component (2 × 30 patients) with progression-free survival as the primary endpoint. Discussion: This study is set up to assess toxicity and first indications of efficacy of MFA repurposed in the setting of a very difficult-to-treat recurrent tumor. The trial is a logical next step after the identification of the role of resistance-providing TMs in glioblastoma, and results will be crucial for further trials targeting TMs. In case of favorable results, MFA may constitute the first clinically feasible TM-targeted drug and therefore might bridge the idea of a TM-targeted therapeutic approach from basic insights into clinical reality. Trial registration: EudraCT 2021-000708-39. Registered on 08 February 2021 [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to determine whether the vertical parasagittal approach or the lateral peri‐insular/peri‐Sylvian approach to hemispheric surgery is the superior technique in achieving long‐term seizure freedom. Methods: We conducted a post hoc subgroup analysis of the HOPS (Hemispheric Surgery Outcome Prediction Scale) study, an international, multicenter, retrospective cohort study that identified predictors of seizure freedom through logistic regression modeling. Only patients undergoing vertical parasagittal, lateral peri‐insular/peri‐Sylvian, or lateral trans‐Sylvian hemispherotomy were included in this post hoc analysis. Differences in seizure freedom rates were assessed using a time‐to‐event method and calculated using the Kaplan–Meier survival method. Results: Data for 672 participants across 23 centers were collected on the specific hemispherotomy approach. Of these, 72 (10.7%) underwent vertical parasagittal hemispherotomy and 600 (89.3%) underwent lateral peri‐insular/peri‐Sylvian or trans‐Sylvian hemispherotomy. Seizure freedom was obtained in 62.4% (95% confidence interval [CI] = 53.5%–70.2%) of the entire cohort at 10‐year follow‐up. Seizure freedom was 88.8% (95% CI = 78.9%–94.3%) at 1‐year follow‐up and persisted at 85.5% (95% CI = 74.7%–92.0%) across 5‐ and 10‐year follow‐up in the vertical subgroup. In contrast, seizure freedom decreased from 89.2% (95% CI = 86.3%–91.5%) at 1‐year to 72.1% (95% CI = 66.9%–76.7%) at 5‐year to 57.2% (95% CI = 46.6%–66.4%) at 10‐year follow‐up for the lateral subgroup. Log‐rank test found that vertical hemispherotomy was associated with durable seizure‐free progression compared to the lateral approach (p =.01). Patients undergoing the lateral hemispherotomy technique had a shorter time‐to‐seizure recurrence (hazard ratio = 2.56, 95% CI = 1.08–6.04, p =.03) and increased seizure recurrence odds (odds ratio = 3.67, 95% CI = 1.05–12.86, p =.04) compared to those undergoing the vertical hemispherotomy technique. Significance: This pilot study demonstrated more durable seizure freedom of the vertical technique compared to lateral hemispherotomy techniques. Further studies, such as prospective expertise‐based observational studies or a randomized clinical trial, are required to determine whether a vertical approach to hemispheric surgery provides superior long‐term seizure outcomes. [ABSTRACT FROM AUTHOR]

The investigation of the human brain at cellular and microcircuit level remains challenging due to the fragile viability of neuronal tissue, inter- and intra-variability of the samples and limited availability of human brain material. Especially brain slices have proven to be an excellent source to investigate brain physiology and disease at cellular and small network level, overcoming the temporal limits of acute slices. Here we provide a revised, detailed protocol of the production and in-depth knowledge on long-term culturing of such human organotypic brain slice cultures for research purposes. We highlight the critical pitfalls of the culturing process of the human brain tissue and present exemplary results on viral expression, single-cell Patch-Clamp recordings, as well as multi-electrode array recordings as readouts for culture viability, enabling the use of organotypic brain slice cultures of these valuable tissue samples for basic neuroscience and disease modeling (Fig. 1). [Display omitted] • Detailed protocol for human brain slice culture production and maintenance. • Long-term human organotypic brain slice cultures are viable for 2-3 weeks. • Viral transduction, whole-cell Patch-Clamp recordings and multi-electrode array recordings. • Correlation between success rates of culturing with the patient age and morbidity. [ABSTRACT FROM AUTHOR]

Background: Meningiomas are common brain tumours that are usually defined by benign clinical course. However, some meningiomas undergo a malignant transformation and recur within a short time period regardless of their World Health Organization (WHO) grade. The current study aimed to identify potential markers that can discriminate between benign and malignant meningioma courses. Methods: We profiled the metabolites from 43 patients with low- and high-grade meningiomas. Tumour specimens were analyzed by nuclear magnetic resonance analysis; 270 metabolites were identified and clustered with the AutoPipe algorithm. Results: We observed two distinct clusters marked by alterations in glycine/serine and choline/tryptophan metabolism. Glycine/serine cluster showed significantly lower WHO grades and proliferation rates. Also progression-free survival was significantly longer in the glycine/serine cluster. Conclusion: Our findings suggest that alterations in glycine/serine metabolism are associated with lower proliferation and more recurrent tumours. Altered choline/tryptophan metabolism was associated with increases proliferation, and recurrence. Our results suggest that tumour malignancy can be reflected by metabolic alterations, which may support histological classifications to predict the clinical outcome of patients with meningiomas. [ABSTRACT FROM AUTHOR]

Background: In recent years, PD-1/PD-L1 immune checkpoint inhibitors have improved cancer therapy in many tumor types, but no benefit of immune checkpoint therapy has been found in glioblastoma multiforme (GBM). Based on the results of our earlier work, which showed a reduction of PD-L1 expression in patients treated with temozolomide (TMZ), we aimed to investigate the link between TMZ therapy and the immune control point target PD-L1.Methods: RNA-sequencing data from de-novo and recurrent glioblastoma were analyzed by AutoPipe algorithm. Results were confirmed either in a cell model by two primary and one established GBM cell line and specimens of de-novo and recurrent GBM. PD-L1 and pathway activation of the JAK/STAT pathway was analyzed by quantitative real-time PCR and western blot.Results: We found a significant downregulation of the JAK/STAT pathway and immune response in recurrent tumors. The cell model showed an upregulation of PD-L1 after IFNγ treatment, while additional TMZ treatment lead to a reduction of PD-L1 expression and JAK/STAT pathway activation. These findings were confirmed in specimens of de-novo and recurrent glioblastoma.Conclusions: Our results suggest that TMZ therapy leads to a down-regulation of PD-L1 in primary GBM cells. These results support the clinical findings where PD-L1 is significantly reduced in recurrent GBMs. If the target is diminished, it may also lead to impaired efficacy of PD-1/PD-L1 inhibitors such as nivolumab. [ABSTRACT FROM AUTHOR]

Background: Oligodendroglioma (ODG) are CNS resistant tumors characterized by their unique molecular signature, namely a combined deletion of 1p and 19q simultaneously to an IDH1/2 mutation. These tumors have a more favorable clinical outcome compared to other gliomas and a long-time survival that ranges between 10 and 20 years. However, during the course of the disease, multiple recurrences occur and the optimal treatment at each stage of the disease remains unclear. Here we report a retrospective longitudinal observation study of 836 MRI examinations in 44 ODG patients.Methods: We quantified the volume of T2-hyperintensity to compute growth behavior in dependence of different treatment modalities, using various computational models.Results: The identified growth pattern revealed dynamic changes, which were found to be patient-specific an did not correlate with clinical parameter or therapeutic interventions. Further, we showed that, surgical resection is beneficial for overall survival regardless the WHO grad or timepoint of surgery. To improve overall survival, an extent of resection above 50% is required. Multiple resections do not generally improve overall survival, except a greater extent of resection than in previous surgeries was achieved.Conclusions: Our data aids to improve the interpretation of MRI images in clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: To review the evidence on the clinical value of magnetic source imaging (MSI) in patients with refractory focal epilepsy without evidence for an epileptogenic lesion on magnetic resonance imaging ("MRI-negative" or "non-lesional MRI")., Methods: We conducted a systematic literature search on PUBMED, which was extended by researchrabbit.ai using predefined criteria to identify studies that applied MSI in MRI-negative patients with epilepsy. We extracted data on patient characteristics, MSI methods, localization results, surgical outcomes, and correlation with other modalities., Results: We included 23 studies with a total of 512 non-lesional epilepsy patients who underwent MSI. Most studies used equivalent current dipole (ECD) models to estimate the sources of interictal epileptic discharges (IEDs). MEG detected IEDs in 32-100% of patients. MSI results were concordant with other modalities, such as EEG, PET, and SPECT, in 3892% of cases. If MSI concordant surgery was performed, 52-89% of patients achieved seizure freedom. MSI contributed to the decision-making process in 28-75% of cases and altered the surgical plan in 5-33% of cases., Conclusions: MSI is a valuable diagnostic tool for MRI-negative patients with epilepsy, as it can detect and localize IEDs with high accuracy and sensitivity, and provides useful information for surgical planning and predicts outcomes. MSI can also complement and refine the results of other modalities, such as EEG and PET, and optimize the use of invasive recordings. MSI should be considered as part of the presurgical evaluation, especially in patients with non-lesional refractory epilepsy.

The human septum verum represents a small but clinically important region of the brain. Based on the results of animal experiments, the stimulation of its medial part was recently proposed with various indications like epilepsy or cognitive impairment after traumatic brain injury. The aim of our study was to present the anatomical relationships of the human septum verum using fiber dissection and histological analysis to support its research and provide essential information for future deep brain stimulation therapies. 16 human cadaveric brains were dissected according to Klingler's method. To validate our macroscopical findings, 12 samples obtained from the dissected brains and 2 additional specimens from unfrozen brains were prepared for histological examinations. We identified the following white matter connections of the septum verum: (1) the precommissural fibers of the fornix; (2) the inferior fascicle of the septum pellucidum; (3) the cingulum; (4) the medial olfactory stria; (5) the ventral amygdalofugal pathway; (6) the stria medullaris of the thalamus and (7) the stria terminalis. Moreover, we could distinguish a less-known fiber bundle connecting the postcommissural column of the fornix to the stria medullaris of the thalamus and the anterior thalamic nuclei. In this study we present valuable anatomical information about this region to promote safe and effective deep brain stimulation therapies in the future., (© 2024. The Author(s).)

Rhythmic brain activity is critical to many brain functions and is sensitive to neuromodulation, but so far very few studies have investigated this activity on the cellular level in vitro in human brain tissue samples. This study reveals and characterizes a novel rhythmic network activity in the human neocortex. Using intracellular patch-clamp recordings of human cortical neurons, we identify large rhythmic depolarizations (LRDs) driven by glutamate release but not by GABA. These LRDs are intricate events made up of multiple depolarizing phases, occurring at ~0.3 Hz, have large amplitudes and long decay times. Unlike human tissue, rat neocortex layers 2/3 exhibit no such activity under identical conditions. LRDs are mainly observed in a subset of L2/3 interneurons that receive substantial excitatory inputs and are likely large basket cells based on their morphology. LRDs are highly sensitive to norepinephrine (NE) and acetylcholine (ACh), two neuromodulators that affect network dynamics. NE increases LRD frequency through β-adrenergic receptor activity while ACh decreases it via M 4 muscarinic receptor activation. Multi-electrode array recordings show that NE enhances and synchronizes oscillatory network activity, whereas ACh causes desynchronization. Thus, NE and ACh distinctly modulate LRDs, exerting specific control over human neocortical activity., (© 2024. The Author(s).)

Background: This research aims to improve glioblastoma survival prediction by integrating MR images, clinical, and molecular-pathologic data in a transformer-based deep learning model, addressing data heterogeneity and performance generalizability., Methods: We propose and evaluate a transformer-based nonlinear and nonproportional survival prediction model. The model employs self-supervised learning techniques to effectively encode the high-dimensional MRI input for integration with nonimaging data using cross-attention. To demonstrate model generalizability, the model is assessed with the time-dependent concordance index (Cdt) in 2 training setups using 3 independent public test sets: UPenn-GBM, UCSF-PDGM, and Rio Hortega University Hospital (RHUH)-GBM, each comprising 378, 366, and 36 cases, respectively., Results: The proposed transformer model achieved a promising performance for imaging as well as nonimaging data, effectively integrating both modalities for enhanced performance (UCSF-PDGM test-set, imaging Cdt 0.578, multimodal Cdt 0.672) while outperforming state-of-the-art late-fusion 3D-CNN-based models. Consistent performance was observed across the 3 independent multicenter test sets with Cdt values of 0.707 (UPenn-GBM, internal test set), 0.672 (UCSF-PDGM, first external test set), and 0.618 (RHUH-GBM, second external test set). The model achieved significant discrimination between patients with favorable and unfavorable survival for all 3 datasets (log-rank P 1.9 × 10 -8 , 9.7 × 10 -3 , and 1.2 × 10 -2 ). Comparable results were obtained in the second setup using UCSF-PDGM for training/internal testing and UPenn-GBM and RHUH-GBM for external testing (Cdt 0.670, 0.638, and 0.621)., Conclusions: The proposed transformer-based survival prediction model integrates complementary information from diverse input modalities, contributing to improved glioblastoma survival prediction compared to state-of-the-art methods. Consistent performance was observed across institutions supporting model generalizability., Competing Interests: The authors declare no conflict of interest in this work., (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

In this issue of Cancer Cell, Zhong et al. explore the dual role of TREM2 in glioblastoma-associated myeloid cells, demonstrating its function in promoting inflammation at the tumor-neural interface and suppression within the tumor core, influenced by the local microenvironment. These findings open up promising prospects for advancements in neuro-oncological immunotherapy., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals a high abundance of malignant stemcell-like cells in high-neural glioblastoma, primarily of the neural lineage. These cells are further classified as neural-progenitor-cell-like, astrocyte-like and oligodendrocyte-progenitor-like, alongside oligodendrocytes and excitatory neurons. In line with these findings, high-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature is associated with decreased overall and progression-free survival. High-neural tumors also exhibit increased functional connectivity in magnetencephalography and resting-state magnet resonance imaging and can be detected via DNA analytes and brain-derived neurotrophic factor in patients' plasma. The prognostic importance of the neural signature was further validated in patients diagnosed with diffuse midline glioma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant. High-neural gliomas likely require a maximized surgical resection approach for improved outcomes., (© 2024. The Author(s).)

Objective: Benchmarking has been proposed to reflect surgical quality and represents the highest standard reference values for desirable results. We sought to determine benchmark outcomes in patients after surgery for drug-resistant mesial temporal lobe epilepsy (MTLE)., Methods: This retrospective multicenter study included patients who underwent MTLE surgery at 19 expert centers on five continents. Benchmarks were defined for 15 endpoints covering surgery and epilepsy outcome at discharge, 1 year after surgery, and the last available follow-up. Patients were risk-stratified by applying outcome-relevant comorbidities, and benchmarks were calculated for low-risk ("benchmark") cases. Respective measures were derived from the median value at each center, and the 75th percentile was considered the benchmark cutoff., Results: A total of 1119 patients with a mean age (range) of 36.7 (1-74) years and a male-to-female ratio of 1:1.1 were included. Most patients (59.2%) underwent anterior temporal lobe resection with amygdalohippocampectomy. The overall rate of complications or neurological deficits was 14.4%, with no in-hospital death. After risk stratification, 377 (33.7%) benchmark cases of 1119 patients were identified, representing 13.6%-72.9% of cases per center and leaving 742 patients in the high-risk cohort. Benchmark cutoffs for any complication, clinically apparent stroke, and reoperation rate at discharge were ≤24.6%, ≤.5%, and ≤3.9%, respectively. A favorable seizure outcome (defined as International League Against Epilepsy class I and II) was reached in 83.6% at 1 year and 79.0% at the last follow-up in benchmark cases, leading to benchmark cutoffs of ≥75.2% (1-year follow-up) and ≥69.5% (mean follow-up of 39.0 months)., Significance: This study presents internationally applicable benchmark outcomes for the efficacy and safety of MTLE surgery. It may allow for comparison between centers, patient registries, and novel surgical and interventional techniques., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Introduction: The surgical procedure for severe, drug-resistant, unilateral hemispheric epilepsy is challenging. Over the last decades the surgical landscape for hemispheric disconnection procedures changed from anatomical hemispherectomy to functional hemispherotomy with a reduction of complications and stable good seizure outcome. Here, a task force of European epilepsy surgeons prepared, on behalf of the EANS Section for Functional Neurosurgery, a consensus statement on different aspects of the hemispheric disconnection procedure., Research Question: To determine history, indication, timing, techniques, complications and current practice in Europe for hemispheric disconnection procedures in drug-resistant epilepsy., Material and Methods: Relevant literature on the topic was collected by a literature search based on the PRISMA 2020 guidelines., Results: A comprehensive overview on the historical development of hemispheric disconnection procedures for epilepsy is presented, while discussing indications, timing, surgical techniques and complications. Current practice for this procedure in European epilepsy surgery centers is provided. At present, our knowledge of long-term seizure outcomes primarily stems from open surgical disconnection procedures. Although minimal invasive surgical techniques in epilepsy are rapidly developing and reported in case reports or small case series, long-term seizure outcome remain uncertain and needs to be reported., Discussion and Conclusion: This is the first paper presenting a European consensus statement regarding history, indications, techniques and complications of hemispheric disconnection procedures for different causes of chronic, drug-resistant epilepsy. Furthermore, it serves as the pioneering document to report a comprehensive overview of the current surgical practices regarding this type of surgery employed in renowned epilepsy surgery centers across Europe., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Open resective surgery remains the main treatment modality for refractory epilepsy, but is often considered a last resort option due to its invasiveness., Research Question: This manuscript aims to provide an overview on traditional as well as minimally invasive surgical approaches in modern state of the art epilepsy surgery., Materials and Methods: This narrative review addresses both historical and contemporary as well as minimal invasive surgical approaches in epilepsy surgery. Peer-reviewed published articles were retrieved from PubMed and Scopus. Only articles written in English were considered for this work. A range of traditional and minimally invasive surgical approaches in epilepsy surgery were examined, and their respective advantages and disadvantages have been summarized., Results: The following approaches and techniques are discussed: minimally invasive diagnostics in epilepsy surgery, anterior temporal lobectomy, functional temporal lobectomy, selective amygdalohippocampectomy through a transsylvian, transcortical, or subtemporal approach, insulo-opercular corticectomies compared to laser interstitial thermal therapy, radiofrequency thermocoagulation, stereotactic radiosurgery, neuromodulation, high intensity focused ultrasound, and disconnection surgery including callosotomy, hemispherotomy, and subpial transections., Discussion and Conclusion: Understanding the benefits and disadvantages of different surgical approaches and strategies in traditional and minimal invasive epilepsy surgery might improve the surgical decision tree, as not all procedures are appropriate for all patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier B.V. on behalf of EUROSPINE, the Spine Society of Europe, EANS, the European Association of Neurosurgical Societies.)

Objectives: Although hemispheric surgeries are among the most effective procedures for drug-resistant epilepsy (DRE) in the pediatric population, there is a large variability in seizure outcomes at the group level. A recently developed HOPS score provides individualized estimation of likelihood of seizure freedom to complement clinical judgement. The objective of this study was to develop a freely accessible online calculator that accurately predicts the probability of seizure freedom for any patient at 1-, 2-, and 5-years post-hemispherectomy., Methods: Retrospective data of all pediatric patients with DRE and seizure outcome data from the original Hemispherectomy Outcome Prediction Scale (HOPS) study were included. The primary outcome of interest was time-to-seizure recurrence. A multivariate Cox proportional-hazards regression model was developed to predict the likelihood of post-hemispheric surgery seizure freedom at three time points (1-, 2- and 5- years) based on a combination of variables identified by clinical judgment and inferential statistics predictive of the primary outcome. The final model from this study was encoded in a publicly accessible online calculator on the International Network for Epilepsy Surgery and Treatment (iNEST) website (https://hops-calculator.com/)., Results: The selected variables for inclusion in the final model included the five original HOPS variables (age at seizure onset, etiologic substrate, seizure semiology, prior non-hemispheric resective surgery, and contralateral fluorodeoxyglucose-positron emission tomography [FDG-PET] hypometabolism) and three additional variables (age at surgery, history of infantile spasms, and magnetic resonance imaging [MRI] lesion). Predictors of shorter time-to-seizure recurrence included younger age at seizure onset, prior resective surgery, generalized seizure semiology, FDG-PET hypometabolism contralateral to the side of surgery, contralateral MRI lesion, non-lesional MRI, non-stroke etiologies, and a history of infantile spasms. The area under the curve (AUC) of the final model was 73.0%., Significance: Online calculators are useful, cost-free tools that can assist physicians in risk estimation and inform joint decision-making processes with patients and families, potentially leading to greater satisfaction. Although the HOPS data was validated in the original analysis, the authors encourage external validation of this new calculator., (© 2023 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Introduction: Hemispherectomy/hemispherotomy has been employed in the management of catastrophic epilepsy. However, initial reports on the associated mortality and morbidity raised several concerns regarding the technique's safety. Their actual, current incidence needs to be systematically examined to redefine hemispherotomy's exact role., Research Question: Our current study examined their incidence and evaluated the association of the various hemispherotomy surgical techniques with the reported complications., Material & Methods: A PRISMA-compliant systematic review and meta-analysis was performed. We searched PubMed, Scopus, and Web of Science until December 2022. Fixed- and random-effects models were employed. Egger's regression test was used for estimating the publication bias, while subgroup analysis was utilized for defining the role of the different hemispherotomy techniques., Results: We retrieved a total of 37 studies. The overall procedure mortality was 5%, with a reported mortality of 7% for hemispherectomy and 3% for hemispherotomy. The reported mortality has decreased over the last 30 years from 32% to 2%. Among the observed post-operative complications aseptic meningitis and/or fever occurred in 33%. Hydrocephalus requiring a shunt insertion occurred in 16%. Hematoma evacuation was necessary in 8%, while subgaleal effusion in another 8%. Infections occurred in 11%. A novel post-operative cranial nerve deficit occurred in 11%, while blood transfusion was necessary in 28% of the cases., Discussion and Conclusion: Our current analysis demonstrated that the evolution from hemispherectomy to hemispherotomy along with neuroanesthesia advances, had a tremendous impact on the associated mortality and morbidity. Hemispherotomy constitutes a safe surgical procedure in the management of catastrophic epilepsies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Despite recent advances in cancer immunotherapy, certain tumor types, such as Glioblastomas, are highly resistant due to their tumor microenvironment disabling the anti-tumor immune response. Here we show, by applying an in-silico multidimensional model integrating spatially resolved and single-cell gene expression data of 45,615 immune cells from 12 tumor samples, that a subset of Interleukin-10-releasing HMOX1 +  myeloid cells, spatially localizing to mesenchymal-like tumor regions, drive T-cell exhaustion and thus contribute to the immunosuppressive tumor microenvironment. These findings are validated using a human ex-vivo neocortical glioblastoma model inoculated with patient derived peripheral T-cells to simulate the immune compartment. This model recapitulates the dysfunctional transformation of tumor infiltrating T-cells. Inhibition of the JAK/STAT pathway rescues T-cell functionality both in our model and in-vivo, providing further evidence of IL-10 release being an important driving force of tumor immune escape. Our results thus show that integrative modelling of single cell and spatial transcriptomics data is a valuable tool to interrogate the tumor immune microenvironment and might contribute to the development of successful immunotherapies., (© 2022. The Author(s).)

Advancements in population neuroscience are spurred by the availability of large scale, open datasets, such as the Human Connectome Project or recently introduced UK Biobank. With the increasing data availability, analyses of brain imaging data employ more and more sophisticated machine learning algorithms. However, all machine learning algorithms must balance generalization and complexity. As the detail of neuroimaging data leads to high-dimensional data spaces, model complexity and hence the chance of overfitting increases. Different methodological approaches can be applied to alleviate the problems that arise in high-dimensional settings by reducing the original information into meaningful and concise features. One popular approach is dimensionality reduction, which allows to summarize high-dimensional data into low-dimensional representations while retaining relevant trends and patterns. In this paper, principal component analysis (PCA) is discussed as widely used dimensionality reduction method based on current examples of population-based neuroimaging analyses., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The applications of artificial intelligence (AI) and machine learning (ML) in modern medicine are growing exponentially, and new developments are fast-paced. However, the lack of trust and appropriate legislation hinder its clinical implementation. Recently, there is a clear increase of directives and considerations on Ethical AI. However, most literature broadly deals with ethical tensions on a meta-level without offering hands-on advice in practice. In this article, we non-exhaustively cover basic practical guidelines regarding AI-specific ethical aspects, including transparency and explicability, equity and mitigation of biases, and lastly, liability., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

In the last decades, modern medicine has evolved into a data-centered discipline, generating massive amounts of granular high-dimensional data exceeding human comprehension. With improved computational methods, machine learning and artificial intelligence (AI) as tools for data processing and analysis are becoming more and more important. At the forefront of neuro-oncology and AI-research, the field of radiomics has emerged. Non-invasive assessments of quantitative radiological biomarkers mined from complex imaging characteristics across various applications are used to predict survival, discriminate between primary and secondary tumors, as well as between progression and pseudo-progression. In particular, the application of molecular phenotyping, envisioned in the field of radiogenomics, has gained popularity for both primary and secondary brain tumors. Although promising results have been obtained thus far, the lack of workflow standardization and availability of multicenter data remains challenging. The objective of this review is to provide an overview of novel applications of machine learning- and deep learning-based radiomics in primary and secondary brain tumors and their implications for future research in the field., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Advancements in neuroimaging and the availability of large-scale datasets enable the use of more sophisticated machine learning algorithms. In this chapter, we non-exhaustively discuss relevant analytical steps for the analysis of neuroimaging data using machine learning (ML), while the field of radiomics will be addressed separately (c.f., Chap. 18 -Radiomics). Broadly classified into supervised and unsupervised approaches, we discuss the encoding/decoding framework, which is often applied in cognitive neuroscience, and the use of ML for the analysis of unlabeled data using clustering., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

For almost a century, classical statistical methods including exponential smoothing and autoregression integrated moving averages (ARIMA) have been predominant in the analysis of time series (TS) and in the pursuit of forecasting future events from historical data. TS are chronological sequences of observations, and TS data are therefore prevalent in many aspects of clinical medicine and academic neuroscience. With the rise of highly complex and nonlinear datasets, machine learning (ML) methods have become increasingly popular for prediction or pattern detection and within neurosciences, including neurosurgery. ML methods regularly outperform classical methods and have been successfully applied to, inter alia, predict physiological responses in intracranial pressure monitoring or to identify seizures in EEGs. Implementing nonparametric methods for TS analysis in clinical practice can benefit clinical decision making and sharpen our diagnostic armory., (© 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Purpose: PET using radiolabeled amino acid [ 18 F]-fluoro-ethyl- L -tyrosine (FET-PET) is a well-established imaging modality for glioma diagnostics. The biological tumor volume (BTV) as depicted by FET-PET often differs in volume and location from tumor volume of contrast enhancement (CE) in MRI. Our aim was to investigate whether a gross total resection of BTVs defined as < 1 cm 3 of residual BTV (PET GTR) correlates with better oncological outcome., Methods: We retrospectively analyzed imaging and survival data from patients with primary and recurrent WHO grade III or IV gliomas who underwent FET-PET before surgical resection. Tumor overlap between FET-PET and CE was evaluated. Completeness of FET-PET resection (PET GTR) was calculated after superimposition and semi-automated segmentation of pre-operative FET-PET and postoperative MRI imaging. Survival analysis was performed using the Kaplan-Meier method and the log-rank test., Results: From 30 included patients, PET GTR was achieved in 20 patients. Patients with PET GTR showed improved median OS with 19.3 compared to 13.7 months for patients with residual FET uptake (p = 0.007; HR 0.3; 95% CI 0.12-0.76). This finding remained as independent prognostic factor after performing multivariate analysis (HR 0.19, 95% CI 0.06-0.62, p = 0.006). Other survival influencing factors such as age, IDH-mutation, MGMT promotor status, and adjuvant treatment modalities were equally distributed between both groups., Conclusion: Our results suggest that PET GTR improves the OS in patients with WHO grade III or IV gliomas. A multimodal imaging approach including FET-PET for surgical planning in newly diagnosed and recurrent tumors may improve the oncological outcome in glioma patients., (© 2021. The Author(s).)

Objective: Ischemic events within the territory of the choroidal artery are an important cause of morbidity after temporal lobe epilepsy (TLE) surgery. The aim of the present study was to evaluate the rate of these ischemic events, their clinical presentation, and impact on patients' health-related quality of life (HRQoL) after TLE surgery., Methods: Four hundred twenty-two consecutive patients undergoing temporal resections for drug-resistant TLE were retrospectively analyzed. All patients underwent presurgical multidisciplinary assessment using a standard protocol comprising clinical, neuroradiological, neuropsychological, and EEG data. Postoperative complications with corresponding imaging, neurological deficits, and disease-specific HRQoL questionnaires were evaluated., Results: The overall complication rate was 7.8% (n = 33). Fourteen patients (3.3%) suffered from ischemic events causing 6 permanent motor deficits, 3 with permanent aphasias, and 6 visual field defects that exceeded quadrantanopia. In 8 patients with anterior choroidal artery infarction, accounting for 57% of all ischemic events, infarction volume correlated positively with the occurrence of new permanent neurological deficits (8666 vs 1692 mm3, p = 0.032). Despite the occurrence of ischemic events, HRQoL improved in 71% of patients. However, infarction volume showed a negative correlation trend with HRQoL (Pearson's r = -0.390, p = 0.094). There was a trend toward increased risk for ischemic events in patients who underwent selective amygdalohippocampectomy compared to patients who underwent anterior temporal lobectomy or temporal lesionectomy (RR 0.96, 95% CI 0.93-0.99, p = 0.08)., Conclusions: Choroidal artery infarctions are rare but relevant complications after TLE surgery, presenting with variable clinical courses ranging from devastating neurological deterioration to complete recovery. Despite the occurrence of postoperative infarction, most patients report improvement of HRQoL after TLE surgery. This study showed that the type of surgery appears to modulate the risk for these ischemic events.

Background: Glioblastoma of the corpus callosum (ccGBM) are rare tumors, with a dismal prognosis marked by a rapid clinical deterioration. For a long time, surgical treatment was not considered beneficial for most patients with such tumors. Recent studies claimed an improved survival for patients undergoing extensive resection, albeit without integration of the molecular profile of the lesions. The purpose of this study was to investigate the effect of biopsy and surgical resection on oncological and functional outcomes in patients with IDH wild-type ccGBM., Methods: We performed a retrospective analysis of our institution's database of patients having been treated for high-grade glioma between 2005 and 2017. Inclusion criteria were defined as follows: patients older than 18 years, histopathological, and molecularly defined IDH wild-type glioma, major tumor mass (at least 2/3) invading the corpus callosum in the sagittal plane with a uni- or bilateral infiltration of the adjacent lobules. Surgical therapy (resection vs. biopsy), extent of resection according to the remaining tumor volume and adjuvant treatment as well as overall survival and functional outcome using the Karnofsky Performance Score (KPS) were analyzed., Results: Fifty-five patients were included in the study, from which the mean age was 64 years and men (n = 34, 61.8%) were more often affected than women (n = 21, 38.2%). Thirty (54.5%) patients were treated with stereotactic biopsy alone, while 25 patients received tumor resection resulting in 14.5% (n = 8) gross-total resections and 30.9% (n = 17) partial resections. The 2-year survival rate after resection was 30% compared to 7% after biopsy (p = 0.047). The major benefit was achieved in the group with gross-total resection, while partial resection failed to improve survival. Neurological outcome measured by KPS did not differ between both groups either pre- or postoperatively., Conclusions: Our study suggests that in patients with corpus callosum glioblastoma, gross-total resection prolongs survival without negatively impacting neurological outcome as compared to biopsy.

Selective amygdalohippocampectomy is an effective treatment for patients with therapy-refractory temporal lobe epilepsy but may cause visual field defect (VFD). Here, we aimed to describe tissue-specific pre- and postoperative imaging correlates of the VFD severity using whole-brain analyses from voxel- to network-level. Twenty-eight patients with temporal lobe epilepsy underwent pre- and postoperative MRI (T1-MPRAGE and Diffusion Tensor Imaging) as well as kinetic perimetry according to Goldmann standard. We probed for whole-brain gray matter (GM) and white matter (WM) correlates of VFD using voxel-based morphometry and tract-based spatial statistics, respectively. We furthermore reconstructed individual structural connectomes and conducted local and global network analyses. Two clusters in the bihemispheric middle temporal gyri indicated a postsurgical GM volume decrease with increasing VFD severity (FWE-corrected p < 0.05). A single WM cluster showed a fractional anisotropy decrease with increasing severity of VFD in the ipsilesional optic radiation (FWE-corrected p < 0.05). Furthermore, patients with (vs. without) VFD showed a higher number of postoperative local connectivity changes. Neither in the GM, WM, nor in network metrics we found preoperative correlates of VFD severity. Still, in an explorative analysis, an artificial neural network meta-classifier could predict the occurrence of VFD based on presurgical connectomes above chance level.

Introduction: Health related quality of life (HRQoL) has become a pivotal outcome parameter after surgery for drug-resistant epilepsy. The aim of the study was to investigate HRQoL and its relationship to seizure outcome, neurological deficits and anxiety after epilepsy surgery in a specific subpopulation of elderly patients., Methods: A total of 85 elderly patients (older than 50 years) answered a standardized HRQoL questionnaire one year after epilepsy surgery. The questionnaire addressed the present self-assessed HRQoL in four subdomains (physical function, cognitive function, mood, social interaction). The questionnaire was based on the "Epilepsy Surgery Inventory-55", adapted for use in German speaking patients and validated by the QOLIE -10 and Beck Depression Inventory., Results: A total of 51 patients (60%) were completely seizure free (ILAE1) at last available outcome (LAO). Permanent neurological deficits were observed in 8 patients (7%). Correlation analysis confirmed significant association between seizure outcome and overall HRQoL (r = -0.368, p < .001). New permanent neurological deficits showed impact on both HRQoL and the "cognitive function" subdomain. Anxiety and subjective assessment of postoperative status were strongly correlated with overall HRQoL (r = 0.692, p < .001 and r = 0.591, p < .001 respectively) and remained as independent prognostic factors in a multivariate regression analysis., Conclusion: Surgery for drug-resistant epilepsy in elderly improves patients' HRQoL. Both seizure freedom and new neurological deficits influence overall HRQoL. Interestingly, anxiety and patients' subjective assessment of postoperative status showed the highest impact on HRQoL in this subpopulation of epilepsy patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Temporal lobe epilepsy (TLE) surgery is still underutilized, especially in the elderly population because of concerns related to postoperative complication rate and cognitive deterioration. The aim of the study was to evaluate surgical data, quality of life and neuropsychological outcome in elderly patients, who underwent resective surgery for drug resistant TLE., Methods and Materials: All patients underwent standardized presurgical assessment including clinical, neuroradiological, neuropsychological, and EEG examination. Elderly were considered all patients being 50 years or above (mean 56 yr., range 50-71 yr.). Neuropsychology was assessed before and after surgery, health-related quality of life (HRQOL) only after surgery., Results: A total of 94 consecutive elderly patients were analyzed. Temporo-mesial resections were performed in 85 patients (90 %). Seizure outcome was available in all patients with a mean follow-up of 5.2 years (1.2-19 ± 3.75 years). 57 patients (60.6 %) were completely seizure free (ILAE 1). The overall morbidity was 10 % including 5 surgical complications and 5 permanent neurological deficits. Neuropsychological assessments in 60 patients showed considerable preoperative impairment, losses in different domains in 25-45 % and gains in about 25 % of the patients. Postoperative HRQOL data was available in 75 patients, revealing significant increase of HRQOL in all domains. Complete seizure freedom was the strongest predictor for postoperative HRQOL (p < 0.001)., Conclusion: Surgery for drug resistant temporal lobe epilepsy is a feasible option for elderly patients as seizure control rates are comparable to the younger population. The acceptable rate of permanent neurological deficits and relevant improvements in quality of life, despite considerable postoperative cognitive impairment, justify surgical resection in properly selected elderly patients., (Copyright © 2020 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Long-term epilepsy-associated tumors (LEATs) represent mostly benign brain tumors associated with drug-resistant epilepsy. The aim of the study was to investigate the specific transcriptional signatures of those tumors and characterize their underlying oncogenic drivers. A cluster analysis of 65 transcriptome profiles from three independent datasets resulted in four distinct transcriptional subgroups. The first subgroup revealed transcriptional activation of STAT3 and TGF-signaling pathways and contained predominantly dysembryoplastic neuroepithelial tumors (DNTs). The second subgroup was characterized by alterations in the MAPK-pathway and up-stream cascades including FGFR and EGFR-mediated signaling. This tumor cluster exclusively contained neoplasms with somatic BRAF V600E mutations and abundance of gangliogliomas (GGs) with a significantly higher recurrence rate (42%). This finding was validated by examining recurrent tumors from the local database exhibiting BRAF V600E in 90% of the cases. The third cluster included younger patients with neuropathologically diagnosed GGs and abundance of the NOTCH- and mTOR-signaling pathways. The transcript signature of the fourth cluster (including both DNTs and GGs) was related to impaired neural function. Our analysis suggests distinct oncological pathomechanisms in long-term epilepsy-associated tumors. Transcriptional activation of MAPK-pathway and BRAF V600E mutation are associated with an increased risk for tumor recurrence and malignant progression, therefore the treatment of these tumors should integrate both epileptological and oncological aspects.

Introduction: Elderly patients constitute an expanding part of our society. Due to a continuously increasing life expectancy, an optimal quality of life is expected even into advanced age. Glioblastoma (GBM) is more common in older patients, but they are still often withheld from efficient treatment due to worry of worse tolerance and have a significantly worse prognosis compared to younger patients. Our retrospective observational study aimed to investigate the therapeutic benefit from a second resection in recurrent glioblastoma of elderly patients., Materials and Methods: We included a cohort of 39 elderly patients (> 65 years) with a second resection as treatment option in the case of a tumor recurrence. A causal inference model was built by multiple non- and semiparametric models, which was used to identify matched patients from our elderly GBM database which comprises 538 patients. The matched cohorts were analyzed by a Cox-regression model adjusted by time-dependent covariates., Results: The Cox-regression analysis showed a significant survival benefit (Hazard Ratio: 0.6, 95% CI 0.36-0.9, p-value = 0.0427) for the re-resected group (18.0 months, 95% CI 13.97-23.2 months) compared to the group without re-resection (10.1 months, 95% CI 8.09-20.9 months). No differences in the co-morbidities or hemato-oncological side effects during chemotherapy could be detected. Anesthetic- and surgical complications were rare and comparable to the complication rate of patients undergoing the first-line resection., Conclusion: Taken together, in elderly patients, re-resection is an acceptable treatment option in the recurrent state of a glioblastoma. The individual evaluation of the patients' medical status as well as the chances of withstanding general anesthesia needs to be done in close interdisciplinary consultation. If these requirements are met, elderly patients benefit from a re-resection.

Background: Anaplastic meningiomas are rare tumors with a poor prognosis, even after complete surgical resection and radiotherapy. There has been limited evidence with respect to the clinical factors and their effects on the course of the disease. Various retrospective studies have not been able to provide clear evidence of standardized treatment, usually presenting contradictory results. The aim of this study was to evaluate the prognostic factors influencing the progression-free survival (PFS) and overall survival (OS) of anaplastic meningiomas, with a particular focus on the roles of the extent of resection and postoperative adjuvant radiotherapy., Methods: Between October 2001 and March 2016, 36 patients with anaplastic meningiomas were treated in our Department of Neurosurgery, of whom 11 underwent gross total resection (GTR) and 18 subtotal resection. Twenty-one patients received postoperative adjuvant radiotherapy, and 8 were treated with surgery alone. GTR (Simpson grades I and II) was associated with significantly improved PFS (P = 0.01) and OS (P = 0.004). Furthermore, adjuvant radiotherapy showed an improvement in PFS (P = 0.01) but not in OS (P = 0.16)., Conclusions: The extent of resection in anaplastic meningiomas is correlated with a better outcome. However, resection alone is not sufficient for the long-term control of anaplastic meningiomas. Adjuvant radiotherapy is an essential component in the adjuvant treatment of anaplastic meningiomas, including for patients undergoing GTR. Further investigations through which to improve adjuvant therapy options are necessary to improve meningioma therapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Reactive astrocytes evolve after brain injury, inflammatory and degenerative diseases, whereby they undergo transcriptomic re-programming. In malignant brain tumors, their function and crosstalk to other components of the environment is poorly understood. Here we report a distinct transcriptional phenotype of reactive astrocytes from glioblastoma linked to JAK/STAT pathway activation. Subsequently, we investigate the origin of astrocytic transformation by a microglia loss-of-function model in a human organotypic slice model with injected tumor cells. RNA-seq based gene expression analysis of astrocytes reveals a distinct astrocytic phenotype caused by the coexistence of microglia and astrocytes in the tumor environment, which leads to a large release of anti-inflammatory cytokines such as TGFβ, IL10 and G-CSF. Inhibition of the JAK/STAT pathway shifts the balance of pro- and anti-inflammatory cytokines towards a pro-inflammatory environment. The complex interaction of astrocytes and microglia cells promotes an immunosuppressive environment, suggesting that tumor-associated astrocytes contribute to anti-inflammatory responses.

Purpose: According to the 2016 WHO classification lower-grade gliomas consist of three groups: IDH-mutated and 1p/19q co-deleted, IDH-mutated and IDH-wildtype tumors. The aim of this study was to evaluate the impact of surgical therapy for lower-grade gliomas with a particular focus on the molecular subgroups., Methods: This is a bi-centric retrospective analysis including 299 patients, who underwent treatment for lower-grade glioma between 1990 and 2016. All tumors were re-classified according to the 2016 WHO classification. Data concerning baseline and tumor characteristics, overall survival, different treatment modalities and functional outcome were analyzed., Results: A total of 112 (37.5%) patients with IDH-mutation and 1p/19q co-deletetion, 86 (28.8%) patients with IDH-mutation and 101 (33.8%) patients with IDH-wildtype tumors were identified. The median overall survival (mOS) differed significantly between the groups (p < 0.001). Surgical resection was performed in 226 patients and showed significantly improved mOS compared to the biopsy group (p = 0.001). Gross total resection (GTR) was associated with better survival (p = 0.007) in the whole cohort as well as in the IDH-mutated and IDH-wildtype groups compared to partial resection or biopsy. IDH-wildtype patients presented a significant survival benefit after combined radio-chemotherapy compared to radio- or chemotherapy alone (p = 0.02). Good clinical status (NANO) was associated with longer OS (p = 0.001)., Conclusion: The impact of surgical treatment on the outcome of lower-grade gliomas depends to a great extent on the molecular subtype of the tumors. Patients with more aggressive tumors (IDH-wildtype) seem to profit from more intensive treatment like GTR, multiple resections and combined radio-/chemotherapy.

Introduction: Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor in adults with peak incidence in patients older than 65 years. These patients are mostly underrepresented in clinical trials and often undertreated due to concomitant diseases. Recently, different therapeutic approaches for elderly patients with GBM were discussed. To date, there is no defined standard treatment. The aim of the present study is to evaluate the functional and oncological outcome in surgical treatment of elderly patients., Materials and Methods: A total of 342 elderly patients aged ≥ 65 years were retrospectively analyzed in our neurosurgical center. Surgical therapy, adjuvant treatment, overall survival (OS) and functional outcome using Karnofsky performance scale (KPS) and Neurological assessment of neuro-oncology-score were analyzed., Results: The median age at GBM diagnosis was 73.4 (IQR 9.28) years. Median overall survival was 7.5 (CI 95% 6.0-9.1) months and median preoperative or postoperative KPS was 80 (IQR 20). Surgical resection was performed in 216 (63.2%) patients, in 125 patients (36.5%) patients a stereotactic biopsy was performed. The median OS was significantly higher in patients with gross total resection (GTR) compared to partial resection and biopsy (10.8 months; CI 95% 9.5-12.3). Patients with combined radio- and chemo-therapy (RCT) showed significant longer OS, particularly MGMT-negative GBM. Higher preoperative KPS was found to be associated with improved overall survival., Conclusion: GTR and adjuvant combined RCT provides benefits for overall survival in elderly patients. Therapy decision should be made in regard to preoperative functional status instead of biological age.