Middle meningeal artery embolization (MMAE) is a promising treatment, as surgical treatment of chronic subdural hematoma (cSDH) still exhibits high recurrence rates. G-MEMBRANE is a single-center, investigator-initiated, prospectively randomized controlled trial (RCT) evaluating the efficacy of adjuvant MMAE. Patients with cSDH requiring surgery were randomly assigned to either surgery plus MMAE or surgery alone. The primary endpoint was cSDH recurrence within 3 months of follow-up. Assuming a risk difference of 20%, an interim analysis was planned after the enrollment of 77 patients. A systematic literature review identified all completed RCTs published between 2015 and 2025. The interim analysis included 93 randomized patients, 64 of whom were available for primary endpoint analysis. The drop-out and lost-to-follow-up rate of 19.1% in the control group and 43.5% in the intervention group were high. Mean age was 74.6 ± 13.3 years, 66.7% patients were male. In the intervention group, 5/26 patients (19.2%) developed recurrent cSDH, compared to 9/38 (23.7%) in the control group (p = 0.672). Revision surgeries were performed in 0% in the intervention group and in 4 (10.5%) of the control group (p = 0.140). No adverse events were related to MMAE. Eight RCTs were included in the systematic review with significant results reported in two large multicenter studies and two small single-center studies regarding "recurrences/reoperation." The small risk difference between the study groups at the time of interim analysis led to the premature termination of the study which remains inconclusive. Considering the limitations and international study results, G-MEMBRANE provides preliminary information on safety and possible recurrence prevention of cSDH using MMAE for routine clinical practice.Trial registration: Prospectively registered on Nov. 11th, 2021 German Clinical Trials Registry (DRKS00020465).

In the multidisciplinary treatment of cerebrovascular diseases, specialists from different disciplines strive to develop patient-specific treatment recommendations. ChatGPT is a natural language processing chatbot with increasing applicability in medical practice. This study evaluates ChatGPT's ability to provide treatment recommendations for patients with unruptured intracranial aneurysms (UIA). Anonymized patient data and radiological reports of 20 patients with UIAs were provided to GPT-4 in a standardized format and used to generate a treatment recommendation for different clinical scenarios. GPT-4 responses were evaluated by a multidisciplinary panel of specialists by means of the Likert scale and subsequently benchmarked against the Unruptured Intracranial Aneurysm Treatment Score (UIATS) as well as the actual treatment decision made by the multidisciplinary institutional neurovascular board (INVB). Agreement between expert raters was measured using linear weighted Fleiss-Kappa coefficient. GPT-4 analyzed individual pathological features of the radiological reports and formulated a corresponding assessment for each aspect. None of the recommendations generated reflected evidence of factual hallucination, although in 25% of the case studies no specific recommendation could be derived from the GPT-4 responses. The expert panel rated the overall quality of the GPT-4 recommendations with a median of 3.4 out of 5 points. The GPT-4 recommendations were congruent with those of the INBI in 65% of cases. Interrater reliability among experts showed moderate to low agreement in the assessment of AI-assisted decision making. GPT-4 appears to be able to process clinical information about UIAs and generate treatment recommendations. However, the level of ambiguity and the utilization of scientific evidence in the recommendations are not yet patient/case specific enough to substitute the decision-making of a multidisciplinary neurovascular board. A prospective evaluation of GPT-4 competence as a companion in decision-making panels is deemed necessary.

Abstract Background The discovery of cellular tumor networks in glioblastoma, with routes of malignant communication extending far beyond the detectable tumor margins, has highlighted the potential of supramarginal resection strategies. Retrospective data suggest that these approaches may improve long-term disease control. However, their application is limited by the proximity of critical brain regions and vasculature, posing challenges for validation in randomized trials. Anterior temporal lobectomy (ATL) is a standardized surgical procedure commonly performed in patients with pharmacoresistant temporal lobe epilepsy. Translating the ATL approach from epilepsy surgery to the neuro-oncological field may provide a model for investigating supramarginal resection in glioblastomas located in the anterior temporal lobe. Methods The ATLAS/NOA-29 trial is a prospective, multicenter, multinational, phase III randomized controlled trial designed to compare ATL with standard gross-total resection (GTR) in patients with newly-diagnosed anterior temporal lobe glioblastoma. The primary endpoint is overall survival (OS), with superiority defined by significant improvements in OS and non-inferiority in the co-primary endpoint, quality of life (QoL; “global health” domain of the European organization for research and treatment of cancer (EORTC) QLQ-C30 questionnaire). Secondary endpoints include progression-free survival (PFS), seizure outcomes, neurocognitive performance, and the longitudinal assessment of six selected domains from the EORTC QLQ-C30 and BN20 questionnaires. Randomization will be performed intraoperatively upon receipt of the fresh frozen section result. A total of 178 patients will be randomized in a 1:1 ratio over a 3-year recruitment period and followed-up for a minimum of 3 years. The trial will be supervised by a Data Safety Monitoring Board, with an interim safety analysis planned after the recruitment of the 57th patient to assess potential differences in modified Rankin Scale (mRS) scores between the treatment arms 6 months after resection. Assuming a median improvement in OS from 17 to 27.5 months, the trial is powered at > 80% to detect OS differences with a two-sided log-rank test at a 5% significance level. Discussion The ATLAS/NOA-29 trial aims to determine whether ATL provides superior outcomes at equal patients’ Qol compared to GTR in anterior temporal lobe glioblastoma, potentially establishing ATL as the surgical approach of choice for isolated temporal glioblastoma and redefining the standard of care for this patient population. Trial registration German Clinical Trials Register (DRKS00035314), registered on October 18, 2024.

Frailty is increasingly recognized as a significant prognostic factor in various conditions. However, its impact on outcomes following spontaneous, nonaneurysmal subarachnoid hemorrhage (naSAH) remains unclear. This study aimed to assess the association between pre-existing frailty and functional outcomes in patients with naSAH. The study cohort was made up of 257 patients treated for naSAH at two neurovascular centers between 2012 and 2021. Frailty prior to naSAH was assessed using the modified frailty index (mFI), with patients classified as nonfrail (mFI 0–1) or frail (mFI ≥ 2). Functional outcomes at 6 months were evaluated using the modified Rankin Scale (mRS), categorized as favorable (mRS 0–2) or unfavorable (mRS 3–6). A multivariable logistic regression analysis was performed to identify independent predictors of unfavorable outcomes. Among 257 naSAH patients, 56 (22

Glioblastoma cells rely on connexin 43 (Cx43)-based gap junctions (GJs) for intercellular communication, enabling them to integrate into a widely branched malignant network. Although there are promising prospects for new targeted therapies, the lack of clinically feasible GJ inhibitors has impeded their adoption in clinical practice. In the present study, we investigated tonabersat (TO), a blood-brain-barrier-penetrating drug with GJ-inhibitory properties, in regard to its potential to disassemble intercellular connectivity in glioblastoma networks. Fluorescence-guided measurements of calcein cell-to-cell transfer were used to study functional intercellular connectivity. Specific DNA fragmentation rates of propidium iodide-stained nuclei were measured as a surrogate readout for cell death using flow cytometry. CRISPR/Cas9-mediated gene editing of Cx43 served as a validation tool of cellular effects related to Cx43 GJ inhibition. 3' mRNA sequencing was performed for molecular downstream analysis. We found that TO reduced intercellular GJ-mediated cytosolic traffic and yielded a significant reduction of tumor microtube (TM) length. TO-mediated inhibition of cellular tumor networks was accompanied by a synergistic effect for temozolomide-induced cell death. CRISPR/Cas9 Cx43-knockout revealed similar results, indicating that TO-mediated inhibitory effects rely on the inhibition of Cx43-based GJs. Gene set enrichment analyses found that GJ-mediated synergistic cytotoxic effects were linked to a significant upregulation of cell death signaling pathways. In conclusion, TO disrupts TM-based network connectivity via GJ inhibition and renders glioblastoma cells more susceptible to cytotoxic therapy. Given its previous use in clinical trials for migraine therapy, TO might harbor the potential of bridging the idea of a GJ-targeted therapeutic approach from bench to bedside.

Therapeutic management of patients with leptomeningeal carcinomatosis (LC) may require treatment of concomitant hydrocephalus (HC) in addition to intrathecal chemotherapy (ITC). Ventriculoperitoneal shunts (VPS) equipped with a valve for manual deactivation of shunt function and a concomitant reservoir for application of ITC pose an elegant solution to both problems. The present study evaluates indication, feasibility, and safety of such a modified shunt/reservoir design (mS/R). All patients with LC aged ≥ 18 years who had undergone mS/R implantation between 2013 and 2020 at the authors’ institution were further analyzed. ITC was indicated following the recommendation of the neuro-oncological tumor board and performed according to a standardized protocol. Sixteen patients with LC underwent mS/R implantation for subsequent ITC and concomitant treatment of HC. Regarding HC-related clinical symptoms, 69% of patients preoperatively exhibited lethargy, 38% cognitive impairment, and 38% (additional) visual disturbances. Postoperatively, 86% of patients achieved subjective improvement of HC-related symptoms. Overall, postoperative complications occurred in three patients (19%). No patient encountered cancer treatment-related complications. The present study describes a combination procedure consisting of a standard VPS-system and a standard reservoir for patients suffering from LC and HC. No cancer treatment-related complications occurred, indicating straightforward handling and thus safety.

The rarity of cerebellar glioblastoma presents a significant challenge in clinical practice due to the lack of extensive prognostic data on long-term survival rates, rendering it an underrepresented entity compared to its supratentorial counterpart. This study aims to analyze potential differences in survival outcome between patients with cerebellar and supratentorial glioblastomas. From 2009 to 2020, 8 patients underwent surgical treatment for cerebellar glioblastoma at the authors’ institution. These patients were individually matched with a cohort of 205 consecutive patients from our institutional database with supratentorial glioblastoma, taking into account key prognostic parameters. Progression-free survival (PFS) and overall survival (OS) rates were compared. Additionally, we performed a systematic literature review to compile further survival data on cerebellar glioblastoma patients. The median OS for cerebellar glioblastoma patients was 18 months (95

OBJECTIVE:Visual acuity (VA) constitutes an important outcome measure in surgery for medial sphenoid wing meningioma (SWM). This study aimed to assess the recovery of tumor-associated impairment of VA and its impact on patient-reported outcome measures (PROMs) as an indication of vision-related quality of life in patients who had undergone surgery for medial SWM. METHODS:From 2009 to 2018, 153 consecutive patients with medial SWM underwent surgical treatment at the authors' institutions. Tumor-associated VA was evaluated both on admission and during postoperative follow-up examinations, using Snellen charts. Multivariable analysis was performed to identify independent predictors for postoperative improvement of VA. PROMs were collected based on the National Eye Institute 25-Item Visual Function Questionnaire. RESULTS:Of patients with medial SWM, 53 of 153 (35%) experienced preoperative impairment of VA. The median preoperative duration of visual symptoms was 12 (IQR 3-17) months for the entire study cohort. Multivariable analysis revealed a preoperative duration of visual symptoms ≤ 4 months to be independently associated with postoperative improvement of VA (p = 0.009). Evaluation of PROMs indicated a superior postoperative qualitative extent in the overall health (p = 0.027) and activities of daily living (p = 0.031) categories if preoperative duration of visual impairment was ≤ 4 months. CONCLUSIONS:The overall preoperative duration of tumor-related visual impairment significantly correlates to the extent of postoperative visual improvement as well as vision-related PROMs in medial SWM surgery. These results might aid in preoperative patient counseling and help optimize decision-making and preoperative estimation of long-term visual outcome.

In recent years, the discovery of functional and communicative cellular tumour networks has led to a new understanding of malignant primary brain tumours. In this review, the authors shed light on the diverse nature of cell‐to‐cell connections in brain tumours and propose an innovative treatment approach to address the detrimental connectivity of these networks. The proposed therapeutic outlook revolves around three main strategies: (a) supramarginal resection removing a substantial portion of the communicating tumour cell front far beyond the gadolinium‐enhancing tumour mass, (b) morphological isolation at the single cell level disrupting structural cell‐to‐cell contacts facilitated by elongated cellular membrane protrusions known as tumour microtubes (TMs), and (c) functional isolation at the single cell level blocking TM‐mediated intercellular cytosolic exchange and inhibiting neuronal excitatory input into the malignant network. We draw an analogy between the proposed therapeutic outlook and the Alcatraz Federal Penitentiary, where inmates faced an impassable sea barrier and experienced both spatial and functional isolation within individual cells. Based on current translational efforts and ongoing clinical trials, we propose the Alcatraz‐Strategy as a promising framework to tackle the harmful effects of cellular brain tumour networks.

Objective: Return to work after spinal surgery is a crucial factor in the recovery process. It can contribute not only to physical rehabilitation but also to psychological well-being. This study aims to evaluate the rate of return to work following elective lumbar spine surgery and identify predictors that predict failure of return to work. Methods: Adult patients who underwent anterior lumbar interbody fusion at two medical centers were retrospectively identified. A standardized telephone interview was conducted for the final analysis to assess the clinical outcomes of these patients. Results: Out of a total of 159 patients, 104 were of working age at the time of the elective surgery. Data were missing for 35 patients, who were thus excluded from the analysis. All patients had a minimum follow-up period of one year. After surgery, 75% of the patients returned to work within a median time of 3 months. Quality of life, back pain, leg pain, and ODI scores, as well as self-reported satisfaction, were significantly better in patients who returned to work (p < 0.05). Tobacco use and previous musculoskeletal surgery were significant predictive factors of failure to return to work. None of the patients who were unemployed prior to surgery returned to work. Conclusions: Our study reveals that 75% of patients returned to work within three months after surgery. The most significant predictor of failure to return to work is being unemployed before surgery. Additionally, preoperative education about postoperative behavior and physical activity could potentially increase the rate.

The COVID-19 (coronavirus disease) pandemic had a severe impact on public health worldwide. A rare but serious complication after administration of adenoviral vaccines against SARS-CoV-2 (AstraZeneca-Oxford and Johnson & Johnson) is vaccine-induced immune thrombotic thrombocytopenia and thrombosis (VITT), which can lead to serious complications such as cerebral venous sinus thrombosis (CVST). CVST itself can cause subarachnoid hemorrhage (SAH) and/or intracerebral hemorrhage (ICH), leading to high mortality due to herniation of brain parenchyma. In those patients, an emergent decompressive hemicraniectomy (DC) is regularly performed. Herein, the authors want to focus on the patients who survive DC following VITT-associated CVST and shed light on the neurosurgical considerations in those patients. We herein propose a treatment algorithm regarding the timing and the perioperative management of cranioplasty. We describe an exemplary case highlighting that special circumstances may result in a more urgent need for autologous cranioplasty than usual, based on individual risk assessment.

Postoperative intensive care unit (ICU) monitoring is an established option to ensure patient safety after resection of newly diagnosed glioblastoma. In contrast, secondary unplanned ICU readmission following complicating events during the initial postoperative course might be associated with severe morbidity and impair initially intended surgical benefit. In the present study, we assessed the prognostic impact of secondary ICU readmission and aimed to identify preoperatively ascertainable risk factors for the development of such adverse events in patients treated surgically for newly diagnosed glioblastoma. Between 2013 and 2018, 240 patients were surgically treated for newly diagnosed glioblastoma at the authors’ neuro-oncological center. Secondary ICU readmission was defined as any unplanned admission to the ICU during initial hospital stay. A multivariable logistic regression analysis was performed to identify preoperatively measurable risk factors for unplanned ICU readmission. Nineteen of 240 glioblastoma patients (8%) were readmitted to the ICU. Median overall survival of patients with unplanned ICU readmission was 9 months compared to 17 months for patients without secondary ICU readmission ( p =0.008). Multivariable analysis identified “preoperative administration of dexamethasone > 7 days” ( p =0.002) as a significant and independent predictor of secondary unplanned ICU admission. Secondary ICU readmission following surgery for newly diagnosed glioblastoma is significantly associated with poor survival and thus may negate surgically achieved prerequisites for further treatment. This underlines the indispensability of precise patient selection as well as the importance of further scientific debate on these highly relevant aspects for patient safety.

OBJECT:Postoperative intensive care unit (ICU) monitoring is a common regime after neurosurgical resection of brain metastasis (BM). In comparison, unplanned secondary readmission to the ICU after initial postoperative treatment course occurs in response to adverse events and might significantly impact patient prognosis. In the present study, we analyzed the potential prognostic implications of unplanned readmission to the ICU and aimed at identifying preoperatively collectable risk factors for the development of such adverse events. METHODS:Between 2013 and 2018, 353 patients with BM had undergone BM resection at the authors' institution. Secondary ICU admission was defined as any unplanned admission to the ICU during the initial hospital stay. A multivariable logistic regression analysis was performed to identify preoperatively identifiable risk factors for unplanned ICU readmission. RESULTS:A total of 19 patients (5%) were readmitted to the ICU. Median overall survival (mOS) of patients with unplanned ICU readmission was 2 months (mo) compared to 13 mo for patients without secondary ICU admission (p<0.0001). Multivariable analysis identified "multiple BM" (p=0.02) and "preoperative CRP levels > 10 mg/dl" (p=0.01) as significant and independent predictors of secondary ICU admission. CONCLUSIONS:Unplanned ICU readmission following surgical therapy for BM is significantly related to poor OS. Furthermore, the present study identifies routinely collectable risk factors indicating patients that are at a high risk for unplanned ICU readmission after BM surgery.

Psychoemotional distress affects patients with cancer, including patients with a diagnosis of a malignant brain tumor. Empathy, professional expertise, and conversational skills are required to ensure successful communication with patients. The purpose of this study was to assess whether knowing the communication needs of patients would be helpful to neuro-oncologists before meeting with them. Patients in our neuro-oncology center were asked to complete the National Comprehensive Cancer Network Distress Thermometer (DT) and a study-specific questionnaire on patients' expectations for communication with the treating physician. The questions targeted issues such as attention/caring and awareness of their disease and prognosis. Importance ratings were compared between patients, with high vs. low distress scores to analyze the impact of distress on the patient's needs in physician-patient communication. A total of 81 patients completed the DT and questionnaire. One third (n = 27) had IDH wild-type astrocytoma, and 42 patients (51.9%) were undergoing therapy for primary or recurrent disease. Mean distress was 4.88 (standard deviation ± 2.64) in the whole cohort, and 56.8% of patients had a high distress score (≥ 5 on a 10-point scale). All issues were assessed as important or very important for communication by the majority of patients, and importance ratings increased in patients with high distress levels for most items. Mean importance ratings correlated significantly with distress scores (p < .001). Distress was increased in neuro-oncology patients. Patients with higher distress levels considered issues of both attention/caring and medical information about the disease as more important than patients with lower distress levels. Using distress assessment may help physicians and advanced practitioners to tailor the contents of their discussion for successful communication with patients.

Join Dr. Randy D'Amico Dr. Jason Sheehan of the Journal of Neuro-Oncology for a discussion with Dr. med Anna-Laura Potthoff and Dr. med Matthias Schneider from the University Hospital Bonn to discuss their latest journal article on the survival after resection of brain metastasis the impact of synchronous versus metachronous metastatic disease.

BACKGROUND:Although the world is experiencing a deficit in the neurosurgical workforce, the number of neurosurgeons in Germany has increased within the last two decades. The aim of the present study was to assess the neurosurgical workforce in Germany, compare it to European countries, and assess structures in neurosurgical departments in Germany.METHODS:Data regarding the number of neurosurgeons in Germany as well as the number of departments, beds, cases, and neurosurgical procedures were gathered. A survey among German neurosurgical departments was performed to assess the structure of neurosurgical care. Furthermore, another survey among European countries was performed to acquire information regarding the number of surgeons and the regulation of training.RESULTS:From 2000 to 2019, the number of board-certified neurosurgeons in Germany increased by 151% from 973 to 2,446. During the same period, the German population increased by only 1% from 82.26 million to 83.17 million. Thus, the number of neurosurgeons per 100,000 inhabitants increased from 1.18 to 2.94. The increase of neurosurgeons is not paralleled by an increase in departments or an increase in neurosurgical procedures within the active neurosurgical departments. In comparison to the participating European countries, where the number of neurosurgeons per 100,000 inhabitants ranged from 0.45 to 2.94, with Germany shows the highest number.CONCLUSIONS:German institutions of medical administration urgently need to consider regulation of neurosurgical specialist training to prevent a further uncontrolled increase in neurosurgeons in a manner that is not adapted to the needs of neurosurgical care for the German population. Actions might include a regulation of entry to the training and of the number of training sites. Furthermore, an integration of non-physician assistant health care professionals and delegation of non-surgical workload from neurosurgeons is necessary. A further increase in neurosurgeons would be associated with a decrease in the surgical caseload per surgeons during training and after board certification, which might compromise the quality of neurosurgical care.