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Objective: Although the operating theatre offers unique didactic opportunities, it can be perceived as an uncomfortable environment by medical students due to the lack of theatre etiquette, time pressure and parallel work of different disciplines. We investigated whether virtual reality (VR) training can significantly reduce some of these fears and improve surgical education for medical students., Methods: We randomly divided a group of 24 medical students and investigated the effects of a VR application (digitally recreated operating theatre tour) and compared it with currently-in-use written instructions for operational tasks in the operating theatre. The parameters analyzed in this study included timekeeping, orientation, and the error rate., Results: Medical students who received a preparational VR training for tasks in the operating theatre showed a statistically significant lower rate of getting stuck (P < 0.03), time to find the operation room (P < 0.01), correct gowning (P < 0.05) and better identification of surgical equipment (P < 0.01). The use of a digitally reconstructed operating theatre using VR led to a significant improvement in orientation and error rate in the behavior of medical students in the operating theatre., Conclusions: Routine VR use as part of clinical training could be beneficial in future medical education., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: COVID-19 has attracted global attention primarily because of the severe acute respiratory symptoms associated with it. However, nearly one third of the patients also present with neurologic symptoms. This report describes a case of a previously healthy woman with acute COVID-19 infection, who developed acute facial nerve palsy and rapid progression to coma due to otogenic brain abscess., Case Description: A 63-year-old woman with acute COVID-19 infection exhibited acute facial nerve paresis, high fever and purulent secretion from her left ear within 48 hours after COVID-19 onset. Cranial CT scan confirmed acute mastoiditis, precipitating an urgent mastoidectomy. A postoperative contrast-enhanced MRI on the same day revealed a subdural empyema, which prompted an urgent craniotomy and decompression. Intraoperative microbiological swabs confirmed a Streptococcus pyogenes infection, however RT-PCR was negative for SARS-CoV-2. After immediate i.v. antibiotic treatment, extubation was achieved four days post-operation, and the patient was discharged without neurologic deficits 19 days after postoperatively., Conclusion: This finding adds a layer of insight into the specific nature of the infection, suggesting a potential absence of SARS-CoV-2 involvement in otogenic subdural empyema. However, the impact of SARS-CoV-2 in otogenic brain abscess cannot be excluded to date and should be further prospectively investigated. The complete recovery of neurological status, emphasizes the importance of prompt and interdisciplinary interventions in managing rare and severe complications associated with COVID-19., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Competing Interests: Dr. Gessler received funding from B. Braun Aesculap, Signus Consulting, and AstraZeneca. Dr. Strzelczyk received funding from Angelini Pharma, Bicodex, Desitin, Eisai, Jazz, Takeda, Union Chimique Belge, and UNEEG Medical. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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.

He, we show that combined use of the EZH2 inhibitor GSK126 and the CDK4/6 inhibitor abemaciclib synergistically enhances antitumoral effects in preclinical GBM models. Dual blockade led to HIF1α upregulation and CalR translocation, accompanied by massive impairment of mitochondrial function. Basal oxygen consumption rate, ATP synthesis, and maximal mitochondrial respiration decreased, confirming disrupted endoplasmic reticulum-mitochondrial homeostasis. This was paralleled by mitochondrial depolarization and upregulation of the UPR sensors PERK, ATF6α, and IRE1α. Notably, dual EZH2/CDK4/6 blockade also reduced 3D-spheroid invasion, partially inhibited tumor growth in ovo, and led to impaired viability of patient-derived organoids. Mechanistically, this was due to transcriptional changes in genes involved in mitotic aberrations/spindle assembly (Rb, PLK1, RRM2, PRC1, CENPF, TPX2), histone modification (HIST1H1B, HIST1H3G), DNA damage/replication stress events (TOP2A, ATF4), immuno-oncology (DEPDC1), EMT-counterregulation (PCDH1) and a shift in the stemness profile towards a more differentiated state. We propose a dual EZH2/CDK4/6 blockade for further investigation., (© 2024. The Author(s).)

Objective: Recent work on ischemic cerebellar stroke has suggested that the resection of infarcted tissue may lead to improved functional outcomes compared with decompressive surgery alone. Nonetheless, no studies have assessed the extent to which necrotic tissue should be resected or if there are any volumetric thresholds capable of predicting functional outcomes in this patient population. In this study, the authors aimed to determine potential thresholds for volume reduction in ischemic cerebellar stroke in an effort to optimize the management of ischemic cerebellar stroke and, in so doing, improve functional outcomes., Methods: This study is a multicentric retrospective study of patients who underwent surgery for the management of ischemic cerebellar stroke. Volumetric analyses of infarcted tissue present on CT scans were performed before and after surgical intervention(s). The final infarct volume (FIV) was computed as a percentage of the initial infarct volume (postoperative infarct volume/preoperative infarct volume × 100). The primary endpoint was functional outcome at 3 months, as determined by the modified Rankin Scale (mRS) score; mRS scores 0-2 were considered as favorable and mRS scores 3-6 as unfavorable. Receiver operating characteristic curves were used to explore the relationship between postoperative infarct volumes and FIV versus mRS score, and Youden's index was used to estimate potential volumetric thresholds., Results: A total of 91 patients were included in the study. The mean pre- and postoperative infarct volumes were 45.25 (SD 18.32) cm3 and 29.56 (SD 26.61) cm3, respectively. Patients undergoing necrosectomy, regardless of whether via craniotomy or craniectomy, were more likely to have a favorable outcome at discharge (OR 16.62, 95% CI 2.12-130.33; p = 0.008) and at 3 months (OR 24.12, 95% CI 3.03-192.18; p = 0.003) postoperatively. Postoperative infarct volumes ≤ 17 cm3 yielded a sensitivity of 77% and a specificity of 68% with regard to the prediction of favorable outcome at 3 months. The resection ≥ 50% of infarcted tissue was also predictive of favorable outcomes at 3 months (OR 7.7, 95% CI 2.7-21.8; p < 0.001)., Conclusions: The reduction of necrotic tissue volumes by at least 50% and/or the reduction of the infarct volume by ≤ 17 cm3 appear to be associated with favorable outcomes in patients with surgically managed ischemic cerebellar strokes.

Glioblastoma is the most common and lethal central nervous system malignancy with a median survival after progression of only 6-9 months. Major biochemical mechanisms implicated in glioblastoma recurrence include aberrant molecular pathways, a recurrence-inducing tumor microenvironment, and epigenetic modifications. Contemporary standard-of-care (surgery, radiation, chemotherapy, and tumor treating fields) helps to control the primary tumor but rarely prevents relapse. Cytoreductive treatment such as surgery has shown benefits in recurrent glioblastoma; however, its use remains controversial. Several innovative treatments are emerging for recurrent glioblastoma, including checkpoint inhibitors, chimeric antigen receptor T cell therapy, oncolytic virotherapy, nanoparticle delivery, laser interstitial thermal therapy, and photodynamic therapy. This review seeks to provide readers with an overview of (1) recent discoveries in the molecular basis of recurrence; (2) the role of surgery in treating recurrence; and (3) novel treatment paradigms emerging for recurrent glioblastoma.

Background: The differentiation of high-grade glioma and brain tumors of an extracranial origin is eminent for the decision on subsequent treatment regimens. While in high-grade glioma, a surgical resection of the tumor mass is a fundamental part of current standard regimens, in brain metastasis, the burden of the primary tumor must be considered. However, without a cancer history, the differentiation remains challenging in the imaging. Hence, biopsies are common that may help to identify the tumor origin. An additional tool to support the differentiation may be of great help. For this purpose, we aimed to identify a biomarker panel based on the expression analysis of a small sample of tissue to support the pathological analysis of surgery resection specimens. Given that an aberrant glutamate signaling was identified to drive glioblastoma progression, we focused on glutamate receptors and key players of glutamate homeostasis., Methods: Based on surgically resected samples from 55 brain tumors, the expression of ionotropic and metabotropic glutamate receptors and key players of glutamate homeostasis were analyzed by RT-PCR. Subsequently, a receiver operating characteristic (ROC) analysis was performed to identify genes whose expression levels may be associated with either glioblastoma or brain metastasis., Results: Out of a total of 29 glutamatergic genes analyzed, nine genes presented a significantly different expression level between high-grade gliomas and brain metastases. Of those, seven were identified as potential biomarker candidates including genes encoding for AMPA receptors GRIA1 , GRIA2 , kainate receptors GRIK1 and GRIK4 , metabotropic receptor GRM3 , transaminase BCAT1 and the glutamine synthetase (encoded by GLUL ). Overall, the biomarker panel achieved an accuracy of 88% (95% CI: 87.1, 90.8) in predicting the tumor entity. Gene expression data, however, could not discriminate between patients with seizures from those without., Conclusion: We have identified a panel of seven genes whose expression may serve as a biomarker panel to discriminate glioblastomas and brain metastases at the molecular level. After further validation, our biomarker signatures could be of great use in the decision making on subsequent treatment regimens after diagnosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lange, Gade, Einsle, Porath, Reichart, Maletzki, Schneider, Henker, Dubinski, Linnebacher, Köhling, Freiman and Kirschstein.)

Background and Objectives: Space-occupying cerebellar stroke (SOCS) when coupled with neurological deterioration represents a neurosurgical emergency. Although current evidence supports surgical intervention in such patients with SOCS and rapid neurological deterioration, the optimal surgical methods/techniques to be applied remain a matter of debate., Methods: We conducted a retrospective, multicenter study of patients undergoing surgery for SOCS. Patients were stratified according to the type of surgery as (1) suboccipital decompressive craniectomy (SDC) or (2) suboccipital craniotomy with concurrent necrosectomy. The primary end point examined was functional outcome using the modified Rankin Scale (mRS) at discharge and at 3 months (mRS 0-3 defined as favorable and mRS 4-6 as unfavorable outcome). Secondary end points included the analysis of in-house postoperative complications, mortality, and length of hospitalization., Results: Ninety-two patients were included in the final analysis: 49 underwent necrosectomy and 43 underwent SDC. Those with necrosectomy displayed significantly higher rate of favorable outcome at discharge as compared with those who underwent SDC alone: 65.3% vs 27.9%, respectively ( P < .001, odds ratios 4.9, 95% CI 2.0-11.8). This difference was also observed at 3 months: 65.3% vs 41.7% ( P = .030, odds ratios 2.7, 95% CI 1.1-6.7). No significant differences were observed in mortality and/or postoperative complications, such as hemorrhagic transformation, infection, and/or the development of cerebrospinal fluid leaks/fistulas., Conclusion: In the setting of SOCS, patients treated with necrosectomy displayed better functional outcomes than those patients who underwent SDC alone. Ultimately, prospective, randomized studies will be needed to confirm this finding., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Importance: According to the current American Heart Association/American Stroke Association guidelines, decompressive surgery is indicated in patients with cerebellar infarcts that demonstrate severe cerebellar swelling. However, there is no universal definition of swelling and/or infarct volume(s) available to support a decision for surgery., Objective: To evaluate functional outcomes in surgically compared with conservatively managed patients with cerebellar infarcts., Design, Setting, and Participants: In this retrospective multicenter cohort study, patients with cerebellar infarcts treated at 5 tertiary referral hospitals or stroke centers within Germany between 2008 and 2021 were included. Data were analyzed from November 2020 to November 2023., Exposures: Surgical treatment (ie, posterior fossa decompression plus standard of care) vs conservative management (ie, medical standard of care)., Main Outcomes and Measures: The primary outcome examined was functional status evaluated by the modified Rankin Scale (mRS) at discharge and 1-year follow-up. Secondary outcomes included the predicted probabilities for favorable outcome (mRS score of 0 to 3) stratified by infarct volumes or Glasgow Coma Scale score at admission and treatment modality. Analyses included propensity score matching, with adjustments for age, sex, Glasgow Coma Scale score at admission, brainstem involvement, and infarct volume., Results: Of 531 included patients with cerebellar infarcts, 301 (57%) were male, and the mean (SD) age was 68 (14.4) years. After propensity score matching, a total of 71 patients received surgical treatment and 71 patients conservative treatment. There was no significant difference in favorable outcomes (ie, mRS score of 0 to 3) at discharge for those treated surgically vs conservatively (47 [66%] vs 45 [65%]; odds ratio, 1.1; 95% CI, 0.5-2.2; P > .99) or at follow-up (35 [73%] vs 33 [61%]; odds ratio, 1.8; 95% CI, 0.7-4.2; P > .99). In patients with cerebellar infarct volumes of 35 mL or greater, surgical treatment was associated with a significant improvement in favorable outcomes at 1-year follow-up (38 [61%] vs 3 [25%]; odds ratio, 4.8; 95% CI, 1.2-19.3; P = .03), while conservative treatment was associated with favorable outcomes at 1-year follow-up in patients with infarct volumes of less than 25 mL (2 [34%] vs 218 [74%]; odds ratio, 0.2; 95% CI, 0-1.0; P = .047)., Conclusions and Relevance: Overall, surgery was not associated with improved outcomes compared with conservative management in patients with cerebellar infarcts. However, when stratifying based on infarct volume, surgical treatment appeared to be beneficial in patients with larger infarct volumes, while conservative management appeared favorable in patients with smaller infarct volumes.

Background incidence of pyogenic spinal infections has increased in recent years. In addition to treating the spinal infection, optimal care also includes identifying the source of the pyogenic spinal infection and the presence of other infections. The aim of this study is to elucidate the prevalence of oral cavity infection (OCI) within this patient cohort. Methods As part of a prospective study conducted from 2016 to 2021, the number of patients with dental infections was investigated by means of an orthopantomogram (OPG) and subsequent dental examination. Results The presence of an oral infection was investigated in 55 (47%) of 118 patients by an OPG, 29 (53%) of whom had a corresponding abnormality of the oral cavity. In addition to the spinal infection, patients with an oral cavity infection revealed an increased incidence of endocarditis, sepsis and brain abscess. A spinal epidural abscess, a multilevel affection of the infection, and an elevated CRP value were also found in patients with a co-existing oral cavity infection. Back pain assessed at admission and 3 months after surgery was also more pronounced in patients with an oral cavity infection. Neurological deficits were often present in patients with spinal and oral cavity infection. Conclusions The presence of an oral cavity infection has proven to be one of the important factors in the detection of the source of the pyogenic spinal infection. In addition, a pronounced spinal affection and frequent co-infections were seen in patients with an oral cavity infection.

Purpose: Chat generative pre-trained transformer (GPT) is a novel large pre-trained natural language processing software that can enable scientific writing amongst a litany of other features. Given this, there is a growing interest in exploring the use of ChatGPT models as a modality to facilitate/assist in the provision of clinical care., Methods: We investigated the time taken for the composition of neurosurgical discharge summaries and operative reports at a major University hospital. In so doing, we compared currently employed speech recognition software (i.e., SpeaKING) vs novel ChatGPT for three distinct neurosurgical diseases: chronic subdural hematoma, spinal decompression, and craniotomy. Furthermore, factual correctness was analyzed for the abovementioned diseases., Results: The composition of neurosurgical discharge summaries and operative reports with the assistance of ChatGPT leads to a statistically significant time reduction across all three diseases/report types: p < 0.001 for chronic subdural hematoma, p < 0.001 for decompression of spinal stenosis, and p < 0.001 for craniotomy and tumor resection. However, despite a high degree of factual correctness, the preparation of a surgical report for craniotomy proved to be significantly lower (p = 0.002)., Conclusion: ChatGPT assisted in the writing of discharge summaries and operative reports as evidenced by an impressive reduction in time spent as compared to standard speech recognition software. While promising, the optimal use cases and ethics of AI-generated medical writing remain to be fully elucidated and must be further explored in future studies., (© 2024. The Author(s).)

Background: Red blood cell (RBC) transfusion in patients undergoing major elective cranial surgery is associated with increased postoperative morbidity and mortality. This study aims to identify the clinical outcome of transfused glioblastoma patients undergoing primary surgical tumor resection and identify risk factors for RBC transfusion., Material and Methods: Between 2009 and 2019, 406 patients underwent elective primary glioblastoma resection. For multivariate analysis to assess risk factors for RBC transfusion, logistic regression was conducted. The impact of RBC transfusion on overall survival was assessed using Kaplan-Meier analysis., Results: In total, 36 (8.9%) patients received RBC transfusion. Preoperative anemia rate was significantly higher in transfused patients compared to patients without RBC transfusion (33.3 vs 6.5%; p<0.0001). Postoperative complications as well as hospital length of stay (LOS) (p<0.0001) were significantly increased in transfused patients compared to non-transfused patients. After multivariate analysis, risk factors for RBC transfusion were preoperative anemia (p<0.0001), intraoperative blood loss (p<0.0001), female gender (p=0.0056) and radiation (p=0.0064). Kaplan-Meier curves revealed that RBC transfusion and being elderly (age ≥75 years) were relevant for overall survival., Discussion: RBC transfusion is associated with increased postoperative morbidity and mortality in patients undergoing elective primary glioblastoma resection. Preoperative anemia and intraoperative blood loss are major risk factors for RBC transfusion. Preoperative anemia management and blood conservation strategies are crucial in patients undergoing elective primary glioblastoma resection.

Background: Temporal muscle thickness (TMT) on cranial CT scans has recently been identified as a prognostic imaging parameter for assessing a patient's baseline frailty. Here, we analyzed whether TMT correlates with Traumatic brain injury (TBI) severity and whether it can be used to predict outcome(s) after TBI., Methods: We analyzed the radiological and clinical data sets of 193 patients with TBI who were admitted to our institution and correlated the radiological data with clinical outcomes after stratification for TMT., Results: Our analyses showed a significant association between high TMT and increased risk for intracranial hemorrhage ( p = 0.0135) but improved mRS at 6 months ( p = 0.001) as compared to patients with low TMT. Congruent with such findings, a lower TMT was associated with falls and reduced outcomes at 6 months ( p < 0.0001 and p < 0.0001)., Conclusion: High TMT was robustly associated with head trauma sequelae but was also associated with good clinical outcomes in TBI patients. These findings consolidate the significance of TMT as an objective marker of frailty in TBI patients; such measurements may ultimately be leveraged as prognostic indicators.

Objectives: Seizures and status epilepticus (SE) are frequent complications of acute subdural hematoma (aSDH) associated with increased morbidity and mortality. Therefore, we aimed to evaluate whether invasive subdural electroencephalogram recording leads to earlier seizure detection and treatment initiation in patients with aSDH., Design: Prospective, single-center, cohort trial., Setting: Neurologic and neurosurgical ICUs of one academic hospital in Germany., Patients: Patients with aSDH undergoing surgical treatment. In total, 76 patients were enrolled in this study, 31 patients (40.8%) were assigned to the invasive electroencephalogram (iEEG) monitoring group and 45 patients (59.2%) to control group., Interventions: The electrode group was implanted with a subdural strip electrode providing up to 7 days of real-time electroencephalogram recording in the neurointensive care unit, whereas the control group received regular normal surface electroencephalograms during the 7-day period. The primary outcomes were the prevalence and time to seizures and SE occurrence. Secondary outcomes included neurologic outcomes assessed using the Glasgow Outcome Scale (GOS) at discharge and 6-month follow-up and the prevalence of focal structural epilepsy within 2 years after discharge., Measurements and Main Results: The trial was stopped after a study committee meeting when the prespecified criteria were met. The iEEG and control groups were well-matched for clinical characteristics at admission. Frequencies of seizures and SE detection were significantly higher in the iEEG group than in the control group (61% vs 15.6%; p < 0.001 and 38.7% vs 11.1%; p = 0.005). Time to seizure and SE detection was significantly earlier (median 29.2 vs 83.8 hr; p = 0.018 and 17.2 vs 83.8 hr; p = 0.033) in the iEEG group than in the control group. Favorable outcomes (GOS 4-5) were more frequently achieved in the iEEG group than in the control group (58% vs 31%; p = 0.065). No significant differences were detected in long-term mortality or post-traumatic epilepsy., Conclusions: Invasive subdural electroencephalogram monitoring is valuable and safe for early seizure/SE detection and treatment and might improve outcomes in the neurocritical care of patients with aSDH., Competing Interests: Drs. Rosenow and Strzelczyk received funding from Angelini Pharma and Desitin Arzneimittel. Dr. Rosenow’s institution received funding from Federal State of Hesse; he received funding from Eisai GmbH, Jazz Pharma, UCB Pharma, and Roche Pharma; and he received support for article research from Federal State of Hesse. Dr. Strzelczyk received funding from GW/Jazz Pharmaceuticals, Eisai, Marinus, Takeda, UCB/Zogenix, and UNEEG medical. Dr. Melzer has received honoraria for lecturing and travel expenses for attending meetings from Biogen Idec, GlaxoSmithKline, Teva, Novartis Pharma, Bayer Healthcare, Fenzyme, Alexion Pharmaceuticals, Fresenius Medical Care, Diamed, UCB Pharma, Angelini Pharma, and BIAL; he has received royalties for consulting from USB Pharma and Alexion Pharmaceuticals; and he has received support from Euroimmun Fresenius Medical Care, Diamed, Alexion Pharmaceuticals, and Novartis Pharma. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2023 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Purpose: The prognosis of patients ≥ 75 years suffering from glioblastoma is poor. Novel therapies are usually reserved for patients ≤ 70 years. In an aging population, treatment of very elderly patients remains a challenge., Methods: Between 2010 and 2018, a total of 977 glioblastoma patients were treated at our institution. Of these, 143 patients were ≥ 75 years at diagnosis. Primary procedure was surgical resection or biopsy followed by adjuvant treatment, whenever possible. We retrospectively investigated overall survival (OS) and potential prognostic factors influencing survival, including Karnofsky Performance Status (KPS), surgical therapy, adjuvant therapy as well as MGMT promotor status., Results: In very elderly patients, median age was 79 years (range: 75-110). Biopsy only was performed in 104 patients; resection was performed in 39 patients. Median OS for the entire cohort was 5.9 months. Univariate analysis showed that KPS at presentation (≥ 70 vs. ≤60), surgery vs. biopsy, adjuvant chemotherapy and adjuvant radiotherapy were significantly associated with OS (6 vs. 3, p < 0.0111; 12 vs. 4, p = 0.0011; 11 vs. 4, p = 0.0003 and 10 vs. 1.5 months, p < 0.0001, respectively). Multivariate analysis confirmed adjuvant radiotherapy (p < 0.0001) and chemotherapy (p = 0.0002) as independent factors influencing OS., Conclusion: For very elderly patients, the natural course of disease without treatment is devastating. These patients benefit from multimodal treatment including adjuvant radiotherapy and chemotherapy. A beneficial effect of resection has not been demonstrated. Treatment options and outcomes should be thoughtfully discussed before treatment decisions are made., (© 2023. The Author(s).)

Glioblastoma is the most common primary brain cancer in adults and represents one of the worst cancer diagnoses for patients. Suffering from a poor prognosis and limited treatment options, tumor recurrences are virtually inevitable. Additionally, treatment resistance is very common for this disease and worsens the prognosis. These and other factors are hypothesized to be largely due to the fact that glioblastoma cells are known to be able to obtain stem-like traits, thereby driving these phenotypes. Recently, we have shown that the in vitro and ex vivo treatment of glioblastoma stem-like cells with the hormonally active form of vitamin D 3 , calcitriol (1α,25(OH) 2 -vitamin D 3 ) can block stemness in a subset of cell lines and reduce tumor growth. Here, we expanded our cell panel to over 40 different cultures and can show that, while half of the tested cell lines are sensitive, a quarter can be classified as high responders. Using genetic and proteomic analysis, we further determined that treatment success can be partially explained by specific polymorphism of the vitamin D 3 receptor and that high responders display a proteome suggestive of blockade of stemness, as well as migratory potential.

Background: Several individual predictors for outcomes in patients with cerebellar stroke (CS) have been previously identified. There is, however, no established clinical score for CS. Therefore, the aim of this study was to develop simple and accurate grading scales for patients with CS in an effort to better estimate mortality and outcomes., Methods: This multicentric retrospective study included 531 patients with ischemic CS presenting to 5 different academic neurosurgical and neurological departments throughout Germany between 2008 and 2021. Logistic regression analysis was performed to determine independent predictors related to 30-day mortality and unfavorable outcome (modified Rankin Scale score of 4-6). By weighing each parameter via calculation of regression coefficients, an ischemic CS-score and CS-grading scale (CS-GS) were developed and internally validated., Results: Independent predictors for 30-day mortality were aged ≥70 years (odds ratio, 5.2), Glasgow Coma Scale score 3 to 4 at admission (odds ratio, 2.6), stroke volume ≥25 cm 3 (odds ratio, 2.7), and involvement of the brain stem (odds ratio, 3.9). When integrating each parameter into the CS-score, age≥70 years and brain stem stroke were assigned 2 points, Glasgow Coma Scale score 3 to 4, and stroke volume≥25 cm 3 1 point resulting in a score ranging from 0 to 6. CS-score of 0, 1, 2, 3, 4, 5, and 6 points resulted in 30-day mortality of 1%, 6%, 6%, 17%, 21%, 55%, and 67%, respectively. Independent predictors for 30-day unfavorable outcomes consisted of all components of the CS-score with an additional variable focused on comorbidities (CS-GS). Except for Glasgow Coma Scale score 3 to 4 at admission, which was assigned 3 points, all other parameters were assigned 1 point resulting in an overall score ranging from 0 to 7. CS-GS of 0, 1, 2, 3, 4, 5, 6, and 7 points resulted in 30-day unfavorable outcome of 1%, 17%, 33%, 40%, 50%, 80%, 77%, and 100%, respectively. Both 30-day mortality and unfavorable outcomes increased with increasing CS-score and CS-GS ( P <0.001)., Conclusions: The CS-score and CS-GS are simple and accurate grading scales for the prediction of 30-day mortality and unfavorable outcome in patients with CS. While the score systems proposed here may not directly impact treatment decisions, it may help discuss mortality and outcome with patients and caregivers., Competing Interests: Disclosures Dr Bernstock reports stock holdings in Treovir, LLC; compensation from POCKiT Diagnostics for consultant services; compensation from Avidea Technologies for consultant services; and compensation from Centile Bio for consultant services. Dr Günther reports compensation from Daiichi Sankyo Company for other services; compensation from Boehringer Ingelheim for other services; compensation from Ipsen Pharma SAS for other services; compensation from PFIZER PHARMA GMBH for other services; compensation from Occlutech GmbH for other services; and grants from Merz Pharmaceuticals GmbH. Dr Konczalla reports compensation from Aesculap AG for other services and compensation from Carl Zeiss Meditec AG for other services. Dr Schaefer reports travel support from Bayer. Dr Senft reports compensation from brainlab for consultant services; compensation from Bayer for expert witness services; and compensation from Stryker for other services. Dr Walter reports grants from Amgen; grants from PFIZER PHARMA GMBH; grants from Bayer Healthcare; grants from Boehringer Ingelheim; grants from Bristol-Myers Squibb; grants from Amarin Pharma Inc; grants from Daiichi Sankyo Europe GmbH; grants from Merz Pharmaceuticals GmbH; and grants from Merz Pharmaceuticals GmbH.

While comprising only 2% of all ischemic strokes, cerebellar strokes are responsible for substantial morbidity and mortality due to their subtle initial presentation and the morbidity of posterior fossa swelling. Furthermore, low temporal muscle thickness (TMT) has recently been identified as a prognostic imaging parameter to assess patient frailty and outcome. We analyzed radiological and clinical data sets of 282 patients with cerebellar ischemic stroke. Our analysis showed a significant association between low TMT, reduced NIHSS and mRS at discharge ( p = 0.035, p = 0.004), and reduced mRS at 12 months ( p = 0.001). TMT may be used as a prognostic imaging marker and objective tool to assess outcomes in patients with cerebellar ischemic stroke., Competing Interests: DD received financial support from Novartis, Fresenius, Inovitro, and Novocure. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dubinski, Won, Mattes, Trnovec, Behmanesh, Cantré, Baumgarten, Dinc, Konczalla, Wittstock, Freiman and Gessler.)

Purpose: The most frequent therapy of hydrocephalus is implantation of ventriculoperitoneal shunts for diverting cerebrospinal into the peritoneal cavity. We compared two adjustable valves, proGAV and proGAV 2.0, for complications resulting in revision surgery., Methods: Four hundred patients undergoing primary shunt implantation between 2014 and 2020 were analyzed for overall revision rate, 1-year revision rate, and revision-free survival observing patient age, sex, etiology of hydrocephalus, implantation site, prior diversion of cerebrospinal fluid, and cause of revision., Results: All data were available of all 400 patients (female/male 208/192). Overall, 99 patients underwent revision surgery after primary implantation. proGAV valve was implanted in 283 patients, and proGAV 2.0 valves were implanted in 117 patients. There was no significant difference between the two shunt valves concerning revision rate (p = 0.8069), 1-year revision rate (p = 0.9077), revision-free survival (p = 0.6921), and overall survival (p = 0.3232). Regarding 1-year revision rate, we observed no significant difference between the two shunt valves in pediatric patients (40.7% vs 27.6%; p = 0.2247). Revision operation had to be performed more frequently in pediatric patients (46.6% vs 24.8%; p = 0.0093) with a significant higher number of total revisions with proGAV than proGAV 2.0 (33 of 59 implanted shunts [55.9%] vs. 8 of 29 implanted shunts [27.6%]; p = 0.0110) most likely due to longer follow-up in the proGAV-group. For this reason, we clearly put emphasis on analyzing results regarding 1-year revision rate., Conclusion: According to the target variables we analyzed, aside from lifetime revision rate in pediatric patients, there is no significant difference between the two shunt valves., (© 2023. The Author(s).)

Background : Air-pouch balloon-assisted probes have proven to be both simple and reliable tools for intracranial pressure (ICP) monitoring. However, we experienced reproducible falsely high ICP measurements when the ICP probe was inserted into the intracerebral hematoma cavity. Thus, the aim of the experimental and translational study was to analyze the influence of ICP probe placement with regard to measured ICP values. Methods : Two Spiegelberg 3PN sensors were simultaneously inserted into a closed drain system and were connected to two separate ICP monitors thereby allowing for simultaneous ICP measurements. This closed system was also engineered to allow for pressure to be gradually increased in a controlled fashion. Once the pressure was verified using two identical ICP probes, one of the probes was coated with blood in an effort to replicate placement within an intraparenchymal hematoma. Pressures recorded using the coated probe and control probe were then recorded and compared across a range of 0-60 mmHg. In an effort to further the translational relevance of our results, two ICP probes were inserted in a patient that presented with a large basal ganglia hemorrhage that met criteria for ICP monitoring. One probe was inserted into the hematoma and the other into brain parenchyma; ICP values were recorded from both probes and the results compared. Results : The experimental set-up demonstrated a reliable correlation between both control ICP probes. Interestingly, the ICP probe covered with clot displayed a significantly higher average ICP value when compared to the control probe between 0 mmHg and 50 mmHg ( p < 0.001); at 60 mmHg, there was no significant difference noted. Critically, this trend in discordance was even more pronounced in the clinical setting with the ICP probe placed within the hematoma cavity having reported significantly higher ICP values as compared to the probe within brain parenchyma. Conclusions : Our experimental study and clinical pilot highlight a potential pitfall in ICP measurement that may result secondary to probe placement within hematoma. Such aberrant results may lead to inappropriate interventions in an effort to address falsely elevated ICPs.

Background: As compared with supratentorial intracerebral hemorrhages (ICH), bleeds that occur within the cerebellum require special consideration given the nature of the posterior fossa., Objective: To validate ICH and ICH grading scale (ICH-GS) scores in patients with cerebellar hemorrhage and examine the outcomes of patients managed surgically as compared with those who underwent conservative treatment., Methods: This observational multicenter study included 475 patients with cerebellar hemorrhage from 9 different neurosurgical departments in Germany between 2005 and 2021. The prognostic accuracy of ICH and ICH-GS scores were calculated by the area under the curve of the receiver operating characteristic curves. Analyzed outcomes were the in-hospital mortality, mortality at 6 months, in-hospital outcome, and outcome at 6 months., Results: Of 403 patients, 252 patients (62.5%) underwent surgical treatment and 151 patients (37.5%) conservative treatment. Both ICH and ICH-GS scores demonstrated good prognostic accuracy regarding both overall mortality and functional outcomes. In those patients presenting with severe cerebellar hemorrhages, ie, ICH score >3 and ICH-GS score >11, overall mortality was significantly lower in surgically treated patients. Mortality was significantly higher in those patients managed surgically who presented with ICH scores 3; in such patients, improved outcomes were noted when the hematoma was treated conservatively., Conclusion: ICH and ICH scores are useful tools for prediction of survival and outcome in patients with cerebellar ICH. Surgical management may be beneficial for those who present with severe cerebellar ICH as reflected by ICH scores >3, while conservative management seems reasonable in patients with lower ICH scores., (Copyright © Congress of Neurological Surgeons 2022. All rights reserved.)

The small, ubiquitin-like modifier (SUMO) is a post-translational modifier with a profound influence on several key biological processes, including the mammalian stress response. Of particular interest are its neuroprotective effects, first recognized in the 13-lined ground squirrel ( Ictidomys tridecemlineatus ), in the context of hibernation torpor. Although the full scope of the SUMO pathway is yet to be elucidated, observations of its importance in managing neuronal responses to ischemia, maintaining ion gradients, and the preconditioning of neural stem cells make it a promising therapeutic target for acute cerebral ischemia. Recent advances in high-throughput screening have enabled the identification of small molecules that can upregulate SUMOylation, some of which have been validated in pertinent preclinical models of cerebral ischemia. Accordingly, the present review aims to summarize current knowledge and highlight the translational potential of the SUMOylation pathway in brain ischemia.

Objective: While outcomes of surgical treatment for spinal meningiomas are well-described within the literature, factors affecting early return to work as well as long-term health related quality of life remain unclear., Methods: In this retrospective study, patients with spinal meningioma and surgical treatment from two university-level neurosurgical institutions between 2008 and 2021 were analyzed. Time to return to work, physical activities and long-term health related quality of life (assessed by telephone interviews using the EQ-5D-5L health status measure and visual analogue scale (EQ VAS) were analyzed., Results: We identified a total of 196 patients who underwent microsurgical resection of spinal meningioma between January 2008 and December 2021. Of those, 130 patients of working age were included and analyzed. The median follow-up time was 96 months. All included patients returned to work. The median time of return to work was 45 days for the whole cohort. Patients who preoperatively performed physical activity returned to work significantly earlier compared to patients who did not ( p < 0.001). Furthermore, younger age ( p = 0.033) and absence of obesity ( p = 0.023) correlated significantly with earlier return to work. Significant differences were also observed in all 5 EQ-5D-5L dimensions between patients with and without preoperative physical activity., Conclusions: Despite the benign nature of spinal meningioma preoperative physical activity and physiological body weight are associated with favorable postoperative outcome, higher quality of life and early return to work.

Background: Arginine auxotrophy constitutes a shortcoming for ~ 30% of glioblastoma multiforme (GBM). Indeed, arginine-depleting therapy using arginine deiminase from Streptococcus pyogenes (SpyADI) has proven activity against GBM in preclinical studies. The good safety profile of SpyADI renders this agent an ideal combination partner for cytostatic therapy., Methods: In this study, we combined the antineoplastic antibiotic Mithramycin A (MitA) with SpyADI to boost single-agent activity and analyzed underlying response mechanisms in-depth., Results: MitA monotherapy induced a time- and dose-dependent cytotoxicity in eight patient-derived GBM cell lines and had a radiosensitizing effect in all but one cell line. Combination treatment boosted the effects of the monotherapy in 2D- and 3D models. The simultaneous approach was superior to the sequential application and significantly impaired colony formation after repetitive treatment. MitA monotherapy significantly inhibited GBM invasiveness. However, this effect was not enhanced in the combination. Functional analysis identified SpyADI-triggered senescence induction accompanied by increased mitochondrial membrane polarization upon mono- and combination therapy. In HROG63, induction of lysosomes was seen after both monotherapies, indicative of autophagy. These cells seemed swollen and had a more pronounced cortically formed cytoskeleton. Also, cytochrome C and endoplasmatic reticulum-stress-associated proteins ATF4 and Calnexin were enhanced in the combination, contributing to apoptosis. Notably, no significant increases in glioma-stemness marker were seen., Conclusions: Therapeutic utilization of a metabolic defect in GBM along with cytostatic therapy provides a novel combination approach. Whether this SpyADI/MitA regimen will provide a safe alternative to combat GBM, will have to be addressed in subsequent (pre-)clinical trials., (© 2023. The Author(s).)

Background: The ongoing war in Ukraine leads to the destruction of critical infrastructure and the displacement of millions of civilians while the necessity for neurosurgical care has increased tremendously. The consequences of this armed conflict on the practice of neurosurgery are uncertain to date., Methods: A cloud-based questionnaire including 10 single- and multiple-choice questions was sent through the email distribution list of the Ukrainian Neurosurgical Society and the Association of Neurosurgeons of Ukraine., Results: Between June 2022 and July 2022, a link to the online survey was distributed to a total of 134 (100%) departments of neurosurgery across Ukraine. After 21 days of being available, a total of 96 questionnaires (72%) returned., Conclusions: The survey highlights the field of activity as well as the severe impact on professional and personal life of Ukrainian neurosurgeons during the ongoing war., (© 2022. The Author(s).)

Purpose: Seizures pose a significant burden in patients with primary and secondary brain tumors during the end-of-life period. A wide range of 6 to 56% of clinically observed epileptic seizures at the end of life has been reported. We aimed to analyse the incidence of epileptic seizures at the end of life in brain tumor patients more accurately using not only clinical but also electrophysiological findings., Methods: This retrospective, single center study included brain tumor patients who died during the stay on the ward or within 7 days after discharge between 01/2015 and 08/2020. Clinical observation of seizures derived from the original medical records and EEG findings (within 45 days prior to death) were analyzed to determine the incidence of seizures in that period., Results: Of the 68 eligible patients, 50 patients (73.5%) suffered from seizures within 45 days prior to death, of which n = 24 had a status epilepticus. The diagnosis of seizures/ status epilepticus was determined either by the presentation of clinical signs in 45 patients and if not, by the detection of a (possible) non-convulsive status epilepticus in the EEG of five patients., Conclusion: In the presence of neurologically trained staff and with the frequent use of routine EEG, we were able to identify seizures and to distinguish status epilepticus from encephalopathy/ hypoactive delirium. We detected a higher incidence of seizures and status epilepticus at the end of life in neurooncological patients than previously reported., (© 2022. The Author(s).)

Background: Reduced temporal muscle thickness (TMT) was verified as an independent negative prognostic parameter for outcome in brain tumor patients. Independent thereof, chronic subdural hematoma (CSDH) is a neurosurgical condition with high recurrence rates and unreliable risk models for poor outcome. Since sarcopenia was associated with poor outcome, we investigated the possible role of TMT and the clinical course of CSDH patients. Methods: This investigation is a single-center retrospective study on patients with CSDH. We analyzed the radiological and clinical data sets of 171 patients with surgically treated CSDH at a University Hospital from 2017 to 2020. Results: Our analysis showed a significant association between low-volume TMT and increased hematoma volume (p < 0.001), poor outcome at discharge (p < 0.001), and reduced performance status at 3 months (p < 0.002). Conclusion: TMT may represent an objective prognostic parameter and assist the identification of vulnerable CSDH patients.

Background: Systemic mastocytosis (SM) is a rare clonal neoplasm driven by KIT D816V and other mutations. Data were collected from the patient perspective on disease burden and included an SM-specific symptom assessment tool., Methods: US adults aged 18 years and older with a self-reported SM diagnosis completed an online TouchStone SM Patient Survey of 100 items, including the 12-item Short-Form Health Survey, the Indolent Systemic Mastocytosis Symptom Assessment Form, and the Work Productivity and Activity Impairment Questionnaire, as well as questions about SM diagnosis, the impact of SM on daily activities, work impairment, and health care use. The results were analyzed using descriptive statistics., Results: Fifty-six individuals completed the survey (89% women; median age, 48 years; mean time since diagnosis, 6.7 years), reporting indolent SM (66%), aggressive SM (9%), smoldering SM (5%), and unknown SM subtype (18%). Over a 1-year recall, respondents reported seeking emergency care for anaphylaxis (30%) and taking three or more prescription medications (52%) for SM. Over one half of patients (54%) reduced their work hours because of SM, and 64% avoided leaving home because of symptoms. A majority of respondents (93%) had experienced ≥10 SM-related symptoms, noting that the most bothersome were anaphylactic episodes (18%), abdominal/stomach pain (16%), diarrhea/loose stools (13%), and fatigue (11%). Whereas an Indolent Systemic Mastocytosis Symptom Assessment Form-derived total symptom score of 28 is used to indicate moderate-to-severe symptoms, the mean total symptom score was 52.7. Mental and physical component summary scores from the 12-item Short-Form Health Survey were below population norms., Conclusions: Patients who were surveyed reported substantial symptom burden and unmet needs because of SM, as evidenced by seeking emergency care and reporting bothersome symptoms, poor quality of life, and reduced work hours and productivity., Lay Summary: The objective of this research was to understand the burden and unmet needs in the rare disease of systemic mastocytosis (SM) to guide future care. Fifty-six patients completed an online survey containing questions about their diagnosis, medications, health care use, quality of life, and SM symptoms. The results demonstrated that SM is associated with severe and burdensome symptoms, anaphylactic events, emergency department visits, use of multiple medications, reduced ability to work, and poor physical and psychological quality of life. These findings suggest the need for future advances to address unmet needs in patients affected by SM., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Systemic mastocytosis (SM) is a rare clonal neoplasm driven by the KIT D816V mutation and has a broad range of debilitating symptoms. In this study, the authors evaluated SM disease perceptions and management strategies among US health care providers (HCPs)., Methods: Hematologist/oncologist (H/O) HCPs and allergist/immunologist (A/I) HCPs who were treating four or more patients with SM completed an online, 51-item TouchStone HCP Survey, which queried provider characteristics, perceptions of disease burden, and current management. Descriptive analyses by specialty and SM subtype were performed., Results: Of 304 HCPs contacted, 111 (37%) met eligibility criteria, including 51% A/I specialists and 49% H/O specialists. On average, the HCPs had 14 years of practice experience and cared for 20 patients with SM. A/I HCPs saw more patients with nonadvanced SM (78%) compared with H/O HCPs, who saw similar proportions of patients with nonadvanced SM (54%) and advanced SM (46%). HCPs reported testing 75% of patients for the KIT D816V mutation and found an estimated prevalence of 47%. On average, HCPs estimated 8 months between symptom onset and SM diagnosis. HCPs reported that 62% of patients with indolent SM felt depressed or discouraged because of symptoms. In terms of treatment goals for SM, both types of specialists prioritized symptom improvement for nonadvanced SM and improved survival for advanced SM while also prioritizing improving patient quality of life., Conclusions: Both A/I and H/O specialists highlighted unmet needs for patients with SM. The HCPs surveyed reported a lower rate of KIT D816V mutations and a perceived shorter time between symptom onset and SM diagnosis compared with published estimates., Lay Summary: Specialists treating systemic mastocytosis (SM) completed a 51-item questionnaire about their clinical practices and perceptions of disease impact. The study included 111 hematology, oncology, allergy, and immunology physicians. Physicians reported that most patients had nonadvanced disease, yet SM symptoms significantly disrupted their patients' lives. Physicians estimated that SM is diagnosed within months of symptom onset, in contrast with published reports of years' long delays reported by patients with SM. This study identified unmet needs that can inform educational and patient management priorities in this rare disease., (© 2022 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Despite the high incidence and multitudes of operative techniques, the risk factors for chronic subdural hematoma (CSDH) recurrence are still under debate and a universal consensus on the pathophysiology is lacking. We hypothesized that clinically inapparent, a low-grade infection could be responsible for CSDH recurrence. This investigation is a single-center prospective observational study including patients with recurrent CSDH. In total, 44 patients with CSDH recurrence received an intraoperative swab-based microbiological test. The intraoperative swab revealed an inapparent low-grade hematoma infection in 29% of the recurrent CSDH cases. The majority (69%) of the identified germs belonged to the staphylococcus genus. We therefore, propose a novel potential pathophysiology for CSDH recurrence., Competing Interests: Author DD received financial support from Novartis, Fresenius, Inovitro, and Novocure. None of these entities were involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dubinski, Won, Trnovec, Gounko, Baumgarten, Warnke, Cantré, Behmanesh, Bernstock, Freiman, Gessler and Sola.)

Elevated intracranial pressure (ICP) with reduced cerebral perfusion pressure is a well-known cause of secondary brain injury. Previously, there have been some reports describing different supra- and infratentorial ICP measurements depending on the location of the mass effect. Therefore, we aimed to perform a systematic review and meta-analysis to clarify the issue of optimal ICP monitoring in the infratentorial mass lesion. A literature search of electronic databases (PUBMED, EMBASE) was performed from January 1969 until February 2021 according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Two assessors are independently screened for eligible studies reporting the use of simultaneous ICP monitoring in the supra- and infratentorial compartments. For quality assessment of those studies, the New Castle Ottawa Scale was used. The primary outcome was to evaluate the value of supra- and infratentorial ICP measurement, and the secondary outcome was to determine the time threshold until equalization of both values. Current evidence surrounding infratentorial ICP measurement was found to be low to very low quality according to New Castle Ottawa Scale. Eight studies were included in the systematic review, four of them containing human subjects encompassing 27 patients with infratentorial pathology. The pooled data demonstrated significantly higher infratentorial ICP values than supratentorial ICP values 12 h after onset (p < 0.05, 95% CI 3.82-5.38) up to 24 h after onset (p < 0.05; CI 1.14-3.98). After 48-72 h, both ICP measurements equilibrated showing no significant difference. Further, four studies containing 26 pigs and eight dogs showed a simultaneous increase of supra- and infratentorial ICP value according to the increase of supratentorial mass volume; however, there was a significant difference towards lower ICP in the infratentorial compartment compared to the supratentorial compartment. The transtentorial gradient leads to a significant discrepancy between supra- and infratentorial ICP monitoring. Therefore, infratentorial ICP monitoring is warranted in case of posterior fossa lesions for at least 48 h., (© 2022. The Author(s).)

Purpose: In patients with pyogenic spondylodiscitis, surgery is considered the treatment of choice to conduct proper debridement, stabilise the spine and avoid extended bed rest, which in turn is a risk factor for complications such as deep vein thrombosis and pulmonary embolism., Methods: We conducted a retrospective clinical study with analysis of a group of 99 patients who had undergone treatment for pyogenic discitis at our institution between June 2012 and August 2017. Included parameters were age, sex, disease pattern, the presence of deep vein thrombosis, resuscitation, in-hospital mortality, present anticoagulation, preexisting comorbidities, tobacco abuse, body mass index, microbiological germ detection and laboratory results., Results: Among the analysed cohort, 12% of the treated patients for pyogenic spondylodiscitis suffered from a radiologically confirmed pulmonary embolism. Coronary heart disease (p < 0.01), female sex (p < 0.01), anticoagulation at admission (p < 0.01) and non-O blood type (p < 0.001) were associated with development of pulmonary embolism. Pulmonary embolism was significantly associated with resuscitation (p < 0.005) and deep vein thrombosis (p < 0.001). Neurosurgery was not associated with increased risk for pulmonary embolism compared to conservative-treated patients (p > 0.05)., Conclusion: Surgery for pyogenic spondylodiscitis was not associated with an elevated risk of pulmonary embolism in our analysis. However, we describe several risk factors for pulmonary embolism in this vulnerable cohort. Prospective studies are necessary to improve prevention and postoperative management in patients with pyogenic spondylodiscitis., (© 2021. The Author(s).)

Purpose: Acute-on-chronic subdural hematoma (acSDH) describes acute bleeding into a chronic subdural hematoma (SDH), after surgery or second trauma. Because seizures are a well-known complication of SDH, associated with substantial morbidity and mortality, we aimed to analyze the incidence of acute symptomatic seizures (ASz), including status epilepticus, and determine the functional outcomes in this specific cohort of patients., Methods: A retrospective analysis was performed, including patients with acSDH who were admitted to our department between 2010 and 2019. The incidence and timely onset of ASz and status epilepticus were evaluated. Functional outcomes at discharge and at 3-6 month follow-up were analyzed based on the modified Rankin scale., Results: Of 506 patients with chronic SDH, 29 patients (5.7%) were diagnosed with acSDH. The overall incidence of ASz and status epilepticus were 72.4% and 10.3%, respectively. Favorable outcomes were identified in 11 patients (52.4%) in the ASz group compared with 6 patients (75%) in the non-ASz group. The mortality rate was higher in the ASz group compared with that in the control group (29% vs 0%). At follow-up, favorable outcomes were similar to those observed at discharge (52.4% in the ASz group and 71.4% in the control group). The mortality rate was still higher in the ASz group, at 32% compared with 14% for the control group., Conclusion: AcSDH has a high risk for ASz, including status epilepticus, and is associated with unfavorable outcomes and high mortality. Thus, prophylactic treatment with antiepileptic drugs should be considered among this specific cohort of patients., (© 2020. The Author(s).)

Glioblastoma (GBM) is a cancer type with high thrombogenic potential and GBM patients are therefore at a particularly high risk for thrombotic events. To date, only limited data on anticoagulation management after pulmonary embolism (PE) in GBM is available and the sporadic use of DOACs remains off-label. A retrospective cohort analysis of patients with GBM and postoperative, thoracic CT scan confirmed PE was performed. Clinical course, follow-up at 6 and 12 months and the overall survival (OS) were evaluated using medical charts and neuroradiological data. Out of 584 GBM patients, 8% suffered from postoperative PE. Out of these, 30% received direct oral anticoagulants (DOACs) and 70% low-molecular-weight heparin (LMWH) for therapeutic anticoagulation. There was no significant difference in major intracranial hemorrhage (ICH), re-thrombosis, or re-embolism between the two cohorts. Although statistically non-significant, a tendency to reduced mRS at 6 and 12 months was observed in the LMWH cohort. Furthermore, patients receiving DOACs had a statistical benefit in OS. In our analysis, DOACs showed a satisfactory safety profile in terms of major ICH, re-thrombosis, and re-embolism compared to LMWH in GBM patients with postoperative PE. Prospective, randomized trials are urgent to evaluate DOACs for therapeutic anticoagulation in GBM patients with PE., (© 2021. The Author(s).)

Introduction: Dysphagia is a common and severe symptom of traumatic brain injury (TBI) affecting up to 78% of patients. It is associated with pneumonia, increased morbidity, and mortality. Although subdural hematoma (SDH) accounts for over 50% of TBI, the occurrence of dysphagia in this subtype has not been investigated yet., Methods: All patients with SDH admitted to the author's institution between the years 2007 and 2020 were included in the study. Patients with SDH and clinical suspicion for dysphagia received a clinical swallowing assessment by a speech and language pathologist (SLP). Furthermore, the severity of dysphagia was rated according to swallowing disorder scale. Functional outcome was evaluated by the Glasgow outcome scale (GOS)., Results: Out of 545 patients with SDH, 71 patients had dysphagia (13%). The prevalence of dysphagia was significantly lower in the surgical arm compared to the conservative arm (11.8 vs. 21.8%; OR 0.23; p = 0.02). Independent predictors for dysphagia were GCS <13 at admission (OR 4.17; p < 0.001), cardiovascular disease (OR 2.29; p = 0.002), and pneumonia (OR 2.88; p = 0.002), whereas the operation was a protective factor (OR 0.2; p < 0.001). In a subgroup analysis, right-sided SDH was an additional predictor for dysphagia (OR 2.7; p < 0.001). Overall, patients with dysphagia improved significantly under the SLP treatment from the initial diagnosis to hospital discharge ( p < 0.01). However, a subgroup of patients with the most severe grade of dysphagia showed no significant improvement. Patients with dysphagia had significantly worse outcomes (GOS 1-3) compared to those without dysphagia (48.8 vs. 26.4%; p < 0.001)., Conclusion: Dysphagia is a frequent symptom in SDH, and the early identification of dysphagia is crucial regarding the initiation of treatment and functional outcome. Surgery is effective in preventing dysphagia and should be considered in high-risked patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Won, Krieger, Dubinski, Gessler, Behmanesh, Freiman, Konczalla, Seifert and Lapa.)

Background: Glioblastoma (GBM) patients are at particularly high risk for thrombotic complications. In the event of a postoperative pulmonary embolism, therapeutic anticoagulation (tAC) is indispensable. The impact of therapeutic anticoagulation on recurrence pattern in GBM is currently unknown., Methods: We conducted a matched-pair cohort analysis of 57 GBM patients with or without tAC that were matched for age, sex, gross total resection and MGMT methylation status in a ratio of 1:2. Patients' characteristics and clinical course were evaluated using medical charts. MRI characteristics were evaluated by two independent authors blinded to the AC status., Results: The morphologic MRI appearance in first GBM recurrence showed a significantly higher presence of multifocal, midline crossing and sharp demarcated GBM recurrence patterns in patients with therapeutic tAC compared to the matched control group. Although statistically non-significant, the therapeutic tAC cohort showed increased survival., Conclusion: Therapeutic anticoagulation induced significant morphologic changes in GBM recurrences. The underlying pathophysiology is discussed in this article but remains to be further elucidated.

Background: The use and effectiveness of intraoperative cell salvage has been analyzed in many surgical specialties. Until now, no data exist evaluating the efficacy of intraoperative cell salvage in cerebral aneurysm surgery., Aim: To evaluate the efficacy and cost effectiveness of intraoperative cell salvage in cerebral aneurysm surgery., Methods: Data were collected retrospectively for all the patients who underwent cerebral aneurysm surgery at our institution between 2013 and 2019. Routinely, we apply blood salvage through autotransfusion. The cases were divided into a ruptured cerebral aneurysm group and a unruptured cerebral aneurysm group., Results: A total of 241 patients underwent cerebral aneurysm clipping. Of all the cerebral aneurysms, 116 were ruptured and 125 were unruptured and clipped electively. Age, location of the aneurysm, postoperative red blood cell count, intraoperative blood loss, and number of allogenic blood cell transfusions were statistically significantly different between the groups. The autotransfusion of salvaged blood could only be facilitated in eight cases with ruptured cerebral aneurysms and in none with unruptured cerebral aneurysms clipped electively ( p < 0.01). Additionally, 35 patients with ruptured cerebral aneurysms and one patient with unruptured cerebral aneurysm required allogenic red blood cell transfusion after surgery, and 71 vs. 2 units of blood were transfused ( p < 0.0001). In terms of cost effectiveness, a total of EUR 45,189 in 241 patients was spent to run the autotransfusion system, while EUR 13,797 was spent for allogenic blood transfusion., Conclusions: The use of cell salvage in patients with unruptured cerebral aneurysm, undergoing elective surgery, is not effective.

Effective antibiotic therapy of cerebral infections such as meningitis or ventriculitis is hindered by low penetration into the cerebrospinal fluid (CSF). Because continuous infusion of meropenem and vancomycin and routine therapeutic drug monitoring (TDM) have been proposed to optimize antimicrobial exposure in ventriculitis patients, an individualized dosing strategy was implemented in our department. We present a retrospective analysis of meropenem and vancomycin concentrations in serum and CSF in the first nine ventriculitis patients treated with continuous infusion and TDM-guided dose optimization aiming at 20-30 mg/L. Median initial dosing was 8.8 g/24 h meropenem and 4.25 g/24 h vancomycin, respectively, resulting in median serum concentrations of 21.3 mg/L for meropenem and 24.5 mg/L for vancomycin and CSF concentrations of 3.4 mg/L for meropenem and 1.7 mg/L for vancomycin. Median CSF penetration was 15% for meropenem and 7% for vancomycin. With initial dosing, all but one patient achieved CSF concentrations above 1 mg/L. Dose adjustment according to TDM ensured sufficient CSF concentrations in all patients within 48 h of treatment. Given the limited penetration, continuous infusion of meropenem and vancomycin based on renal function and TDM-guided dose optimization appears a reasonable approach to attain sufficient CSF concentrations in ventriculitis patients.

Purpose: Dexamethasone (Dex) is the most common corticosteroid to treat edema in glioblastoma (GBM) patients. Recent studies identified the addition of Dex to radiation therapy (RT) to be associated with poor survival. Independently, Tumor Treating Fields (TTFields) provides a novel anti-cancer modality for patients with primary and recurrent GBM. Whether Dex influences the efficacy of TTFields, however, remains elusive., Methods: Human GBM cell lines MZ54 and U251 were treated with RT or TTFields in combination with Dex and the effects on cell counts and cell death were determined via flow cytometry. We further performed a retrospective analysis of GBM patients with TTFields treatment +/- concomitant Dex and analysed its impact on progression-free (PFS) and overall survival (OS)., Results: The addition of Dex significantly reduced the efficacy of RT in U251, but not in MZ54 cells. TTFields (200 kHz/250 kHz) induced massive cell death in both cell lines. Concomitant treatment of TTFields and Dex did not reduce the overall efficacy of TTFields. Further, in our retrospective clinical analysis, we found that the addition of Dex to TTFields therapy did not influence PFS nor OS., Conclusion: Our translational investigation indicates that the efficacy of TTFields therapy in patients with GBM and GBM cell lines is not affected by the addition of Dex., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Linder, Schiesl, Voss, Rödel, Hehlgans, Güllülü, Seifert, Kögel, Senft and Dubinski.)

Transfusion of red blood cells (RBC) in patients undergoing major elective cranial surgery is associated with increased morbidity, mortality and prolonged hospital length of stay (LOS). This retrospective single center study aims to identify the clinical outcome of RBC transfusions on skull base and non-skull base meningioma patients including the identification of risk factors for RBC transfusion. Between October 2009 and October 2016, 423 patients underwent primary meningioma resection. Of these, 68 (16.1%) received RBC transfusion and 355 (83.9%) did not receive RBC units. Preoperative anaemia rate was significantly higher in transfused patients (17.7%) compared to patients without RBC transfusion (6.2%; p = 0.0015). In transfused patients, postoperative complications as well as hospital LOS was significantly higher ( p < 0.0001) compared to non-transfused patients. After multivariate analyses, risk factors for RBC transfusion were preoperative American Society of Anaesthesiologists (ASA) physical status score ( p = 0.0247), tumor size ( p = 0.0006), surgical time ( p = 0.0018) and intraoperative blood loss ( p < 0.0001). Kaplan-Meier curves revealed significant influence on overall survival by preoperative anaemia, RBC transfusion, smoking, cardiovascular disease, preoperative KPS ≤ 60% and age (elderly ≥ 75 years). We concluded that blood loss due to large tumors or localization near large vessels are the main triggers for RBC transfusion in meningioma patients paired with a potential preselection that masks the effect of preoperative anaemia in multivariate analysis. Further studies evaluating the impact of preoperative anaemia management for reduction of RBC transfusion are needed to improve the clinical outcome of meningioma patients.

Given the ongoing global SARS-CoV-2-vaccination efforts, clinical awareness needs to be raised regarding the possibility of an increased incidence of SARS-CoV-2-vaccine-related immune-mediated thrombocytopenia in patients with intracerebral hemorrhage (ICH) secondary to cerebral sinus and vein thrombosis (CVT) requiring (emergency) neurosurgical treatment in the context of vaccine-induced immune thrombotic thrombocytopenia (VITT). Only recently, an association of vaccinations and cerebral sinus and vein thrombosis has been described. In a number of cases, neurosurgical treatment is warranted for these patients and special considerations are warranted when addressing the perioperative coagulation. We, herein, describe the past management of patients with VITT and established a literature-guided algorithm for the treatment of patients when addressing the impaired coagulation in these patients. Increasing insights addressing the pathophysiology of SARS-CoV-2-vaccine-related immune-mediated thrombocytopenia guide physicians in developing an interdisciplinary algorithm taking into account the special considerations of this disease.

Objective: The aim of this study was to evaluate functional outcome, surgical morbidity, and factors that affect outcomes of surgically treated patients., Methods: The authors retrospectively analyzed patients who underwent microsurgical resection for spinal meningiomas between 2009 and 2020. Patient data and potential variables were collected and evaluated consecutively. Functional outcomes were evaluated using univariate and multivariate analyses., Results: A total of 119 patients underwent microsurgical resection of spinal meningioma within the study period. After a mean follow-up of 25.4 ± 37.1 months, the rates of overall complication, tumor recurrence, and poor functional outcome were 9.2%, 7.6%, and 5%, respectively. Age, sex, revision surgery, and tumor recurrence were identified as independent predictors of poor functional outcome. Obesity and surgeon's experience had an impact on the complication rate, whereas extent of resection and tumor calcification affected the rate of tumor recurrence., Conclusions: Microsurgical resection of spinal meningiomas remains safe. Nevertheless, some aspects, such as obesity and experience of the surgeons that result in a higher complication rate and ultimately affect clinical outcome, should be considered when performing surgery.

Along with increasing average life expectancy, the number of elderly meningioma patients has grown proportionally. Our aim was to evaluate whether these specific patients benefit from surgery and to investigate a previously published score for decision-making in meningioma patients (SKALE). Of 421 patients who underwent primary intracranial meningioma resection between 2009 and 2015, 71 patients were ≥70 years of age. We compared clinical data including World Health Organization (WHO) grade, MIB-1 proliferation index, Karnofsky Performance Status Scale (KPS), progression free survival (PFS) and mortality rate between elderly and all other meningioma patients. Preoperative SKALE scores (Sex, KPS, ASA score, location and edema) were determined for elderly patients. SKALE ≥8 was set for dichotomization to determine any association with outcome parameters. In 71 elderly patients (male/female 37/34) all data were available. Postoperative KPS was significantly lower in elderly patients ( p < 0.0001). Pulmonary complications including pneumonia (10% vs. 3.2%; p = 0.0202) and pulmonary embolism (12.7% vs. 6%; p = 0.0209) occurred more frequently in our elderly cohort. Analyses of the Kaplan Meier curves revealed differences in three-month (5.6% vs. 0.3%; p = 0.0033), six-month (7% vs. 0.3%; p = 0.0006) and one-year mortality (8.5% vs. 0.3%; p < 0.0001) for elderly patients. Statistical analysis showed significant survival benefit in terms of one-year mortality for elderly patients with SKALE scores ≥8 (5.1 vs. 25%; p = 0.0479). According to our data, elderly meningioma patients face higher postoperative morbidity and mortality than younger patients. However, resection is reasonable for selected patients, particularly when reaching a SKALE score ≥ 8.

Research on chronic subdural hematoma (cSDH) management has primarily focused on potential recurrence after surgical evacuation. Herein, we present a novel postoperative/non-invasive treatment that includes a supervised Valsalva maneuver (SVM), which may serve to reduce SDH recurrence. Accordingly, the aims of the study were to investigate the effects of SVM on SDH recurrence rates and functional outcomes. A prospective study was conducted from December 2016 until December 2019 at the Goethe University Hospital Frankfurt. Of the 204 adult patients with surgically treated cSDH who had subdural drains placed, 94 patients were assigned to the SVM group and 82 patients were assigned to the control group. The SVM was performed by having patients blow into a self-made SVM device at least two times/h for 12 h/day. The primary end-point was SDH recurrence rate, while secondary outcomes were morbidity and functional outcomes at 3 months of follow-up. SDH recurrence was observed in 16 of 94 patients (17%) in the SVM group, which was a significant reduction as compared with the control group, which had 24 of 82 patients (29.3%; p  = 0.05) develop recurrent SDHs. Further, the infection rate (e.g., pneumonia) was significantly lower in the SVM group (1.1%) than in the control group (13.4%; p  < 0.001; odds ratio [OR] 0.1). At the 3-month follow-up, 85 of 94 patients (90.4%) achieved favorable outcomes in the SVM group compared with 62 of 82 patients (75.6%) in the control group ( p  = 0.008; OR 3.0). Independent predictors for favorable outcome at follow-up were age (OR 0.9) and infection (OR 0.2). SVM appears to be safe and effective in the post-operative management of cSDHs, reducing both recurrence rates and infections after surgical evacuation, thereby resulting in favorable outcomes at follow-up.

Recently, Oslo grading system (OGS) for prediction of recurrence in chronic subdural hematoma (cSDH) was introduced. The aim of the study was to validate and if applicable to modify the grading system. Data of all patients admitted to the Goethe University Hospital between 2016 and 2018 with chronic subdural hematoma were prospectively entered into a database. Dataset of patients with uni- (n = 272) and bilateral cSDH (n = 177) were used for the validation of OGS via logistic regression analysis. Additional predictors were identified and integrated to build a modified OGS (mOGS). Internal validation of the modified OGS was performed using same dataset of patients. The OGS showed a significant good predictive value with correlating increase of recurrence rate depending on the level of score in unilateral cSDH (p = 0.002). Regarding bilateral cSDH, there was no significant predictive value found (p = 0.921). By performing uni- and multivariate analysis, additional predictors for recurrence in uni- and bilateral cSDH were identified and integrated into the score system. Accordingly, the mOGS for unilateral cSDH inherited 4 components: previous OGS with 3 components (OR1.6) and seizure (OR2.5) (0 point, 0% recurrence rate; 1-2 points, 17.4%; 3-4 points, 30.6%; ≥ 5 points, 80%). Regarding bilateral cSDH, the mOGS consisted of 4 components as well: hypodense/gradation subtypes (OR3.3), postoperative unilateral volume > 80 mL (OR7.4), postoperative unilateral air trapping > 80 mL (OR15.3), and seizure (OR5.5) (0 point, 3.6% recurrence rate; 1 point, 30.6%; 2 points, 53.5%; 3 points, 58.3%; ≥ 4 points, 100%). Furthermore, the mOGS was internally verified showing high significant predictive power for recurrent hematoma in uni- (p = 0.004) and bilateral cSDH (p < 0.001). External validation of OGS showed accurate risk stratification of recurrence in unilateral cSDH; however, the validation failed for bilateral cSDH. Thus, mOGS was developed to strengthen its clinical utility and applicability.

Pulmonary embolism (PE) due to deep vein thrombosis is a complication with severe morbidity and mortality rates. Neurocritical care patients constitute an inhomogeneous cohort with often strict contraindications to conventional embolism treatment. The aim of the present study is to identify risk factors for pulmonary embolism for intensified risk stratification in this demanding cohort. In this retrospective analysis, 387 neurocritical care patients received computed tomography for clinical suspicion of PE (304 neurosurgical and 83 neurological patients). Analysed parameters included age, gender, disease pattern, the presence of deep vein thrombosis, resuscitation, in-hospital mortality, present anticoagulation, coronary artery disease, diabetes mellitus, smoking status, hypertension and ABO blood type. Computed tomography confirmed 165 cases of pulmonary embolism among 387 patients with clinical suspicion of pulmonary embolism (42%). Younger age (p < 0.0001), female gender (p < 0.006), neurooncological disease (p < 0.002), non-O blood type (p < 0.002) and the absence of Marcumar therapy (p < 0.003) were identified as significant risk factors for pulmonary embolism. On the basis of the identified risk factors, the AMBOS score system is introduced. Neurocritical care patients with high AMBOS score are at elevated risk for PE and should therefore be put under intensified monitoring for cardiovascular events in neurocritical care units.

Purpose: The extent of preoperative peritumoral edema in glioblastoma (GBM) has been negatively correlated with patient outcome. As several ongoing studies are investigating T-cell based immunotherapy in GBM, we conducted this study to assess whether peritumoral edema with potentially increased intracranial pressure, disrupted tissue homeostasis and reduced local blood flow has influence on immune infiltration and affects survival., Methods: A volumetric analysis of preoperative imaging (gadolinium enhanced T1 weighted MRI sequences for tumor size and T2 weighted sequences for extent of edema (including the infiltrative zone, gliosis etc.) was conducted in 144 patients using the Brainlab® software. Immunohistochemical staining was analyzed for lymphocytic- (CD 3+) and myelocytic (CD15+) tumor infiltration. A retrospective analysis of patient-, surgical-, and molecular characteristics was performed using medical records., Results: The edema to tumor ratio was neither associated with progression-free nor overall survival (p=0.90, p=0.74). However, GBM patients displaying IDH-1 wildtype had significantly higher edema to tumor ratio than patients displaying an IDH-1 mutation (p=0.01). Immunohistopathological analysis did not show significant differences in lymphocytic or myelocytic tumor infiltration (p=0.78, p=0.74) between these groups., Conclusion: In our cohort, edema to tumor ratio had no significant correlation with immune infiltration and outcome. However, patients with an IDH-1wildtype GBM had a significantly higher edema to tumor ratio compared to their IDH-1 mutated peer group. Further studies are necessary to elucidate the underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Dubinski, Won, Rauch, Behmanesh, Ngassam, Baumgarten, Senft, Harter, Bernstock, Freiman, Seifert and Gessler.)

To clip or coil has been matter of debates for several years and is the domain of interdisciplinary decision making. However, the microsurgical outcome has still been elusive concerning wide neck aneurysms (WNA). A retrospective single center study was performed with all patients with ruptured WNA (rWNA) and unruptured WNA (uWNA) admitted to author´s institute between 2007-2017. Microsurgical outcome was evaluated according to Raymond-Roy occlusion grade and follow-up angiography was performed to analyze the stability of neck/aneurysm remnants and retreatment poverty. Of 805 aneurysms, 139 were rWNA (17.3%) and 148 uWNA (18.4%). Complete occlusion was achieved in 102 of 139 rWNA (73.4%) and 112 of 148 uWNA (75.6%). Neck remnants were observed in 36 patients with rWNA (25.9%) and 30 patients with uWNA (20.3%), 1 (0.7%) and 6 (4.1%) patients had aneurysmal remnant, respectively. Overall complication rate was 11.5%. At follow-up (939/1504 months), all remnants were stable except for one, which was further conservatively treated with marginal retreatment rate under 1%. Even the risk of de-novo aneurysm was higher than the risk for remnant growth (2.6% vs 0% in rWNA; 8.7% vs 5.3% in uWNA) without significant difference. Microsurgical clipping is effective for complete occlusion of r/uWNA with low complication. Furthermore, the risk of remnant growth is marginal even lower than the risk of de-novo rate low retreatment rate.