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Neurocytomas represent 0.25 to 0.5% of primary brain tumours and are mainly found in young adults. These tumours have neuronal differentiation. The cornerstone treatment is neurosurgery. The efficacy of other therapies, including radiotherapy, is still unclear. The objective of this study was to evaluate the management of central neurocytomas and the role of radiotherapy. All adult patients (age 18 years or older) newly diagnosed with a histologically confirmed neurocytoma between 2006 and 2015 in France were included. One hundred and sixteen patients were diagnosed with a central neurocytoma during the study period. All patients underwent surgical resection, and six received adjuvant radiotherapy. Eleven patients received radiotherapy due to progression. After a median follow-up of 68.7 months, local failure occurred in 29 patients. The 5-year local control rate was 73.4%. According to univariate analysis, marker of proliferation Ki67 index greater than 2% (hazard ratio [HR]: 1.48; confidence interval [CI]: 1.40–1.57; P = 0.027) and subtotal resection (HR: 8.48; CI: 8.01–8.99; P < 0.001) were associated with an increase in local failure. Gross total resection was associated with a higher risk of sequelae epilepsy (HR: 3.62; CI: 3.42–3.83; P < 0.01) and memory disorders (HR: 1.35; CI: 1.07–1.20; P < 0.01). Ten patients (8.6%) died during the follow-up. The 10-year overall survival rate was 89.0%. No prognostic factors for overall survival were found. The analysis showed that patients who underwent subtotal surgical resection, particularly when the tumour had a Ki67 index greater than 2%, had an increased risk of local recurrence. These patients could benefit from adjuvant radiotherapy. [ABSTRACT FROM AUTHOR]

Background: Non-invasive brain mapping using navigated transcranial magnetic stimulation (nTMS) is a valuable tool prior to resection of malignant brain tumors. With nTMS motor mapping, it is additionally possible to analyze the function of the motor system and to evaluate tumor-induced neuroplasticity. Distinct changes in motor cortex excitability induced by certain malignant brain tumors are a focal point of research. Methods: A retrospective single-center study was conducted involving patients with malignant brain tumors. Clinical data, resting motor threshold (rMT), and nTMS-based tractography were evaluated. The interhemispheric rMT-ratio (rMTTumor/rMTControl) was calculated for each extremity and considered pathological if it was >110% or <90%. Distances between the corticospinal tract and the tumor (lesion-to-tract-distance -- LTD) were measured. Results: 49 patients were evaluated. 16 patients (32.7%) had a preoperative motor deficit. The cohort comprised 22 glioblastomas (44.9%), 5 gliomas of Classification of Tumors of the Central Nervous System (CNS WHO) grade 3 (10.2%), 6 gliomas of CNS WHO grade 2 (12.2%) and 16 cerebral metastases (32.7%). 26 (53.1%) had a pathological rMT-ratio for the upper extremity and 35 (71.4%) for the lower extremity. All patients with tumor-induced motor deficits had pathological interhemispheric rMT-ratios, and presence of tumor-induced motor deficits was associated with infiltration of the tumor to the nTMS-positive cortex (p = 0.04) and shorter LTDs (all p<0.021). Pathological interhemispheric rMT-ratio for the upper extremity was associated with cerebral metastases, but not with gliomas (p = 0.002). Conclusions: Our study underlines the diagnostic potential of nTMS motor mapping to go beyond surgical risk stratification. Pathological alterations in motor cortex excitability can be measured with nTMS mapping. Pathological cortical excitability was more frequent in cerebral metastases than in gliomas. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 40-year-old man with two asynchronous spinal cord tumors. The patient initially presented with bladder dysfunction and radicular pain, and an emergency lumbar MRI revealed a vertebral disc herniation. Subsequent MRI imaging revealed a contrast-enhancing intramedullary lesion at a different spinal level. The patient underwent surgery for both tumors, and histopathological and DNA methylation analysis confirmed distinct diagnoses for each tumor. The article emphasizes the importance of molecular diagnostics in guiding therapeutic decisions for spinal ependymomas. [Extracted from the article]

Simple Summary: Early characterization of the isocitrate dehydrogenase (IDHIDH) gene mutation status of glioma is crucial for personalized decision making and prognosis in clinical neurooncological treatment. Based on the known differences in energy metabolism between IDHIDH-mutated and IDHIDH-wildtype gliomas, we assessed physio-metabolic magnetic resonance imaging-based measures along with machine learning for potential reliable presurgical characterization of IDHIDH gene status. Traditional machine learning algorithms and simple deep learning models trained in analyzing physio-metabolic parameters demonstrated the best performance in classifying the IDHIDH gene status of gliomas in independent internal testing. In contrast, external testing revealed that traditional machine learning models trained on clinical MRI data had higher accuracy compared to physio-metabolic algorithms, reflecting differences in data acquisition methodology between the two sites. Our results outline the necessity of independent internal and external testing, thus calling for standardized and robust protocols for clinical MRI-driven AI applications. The mutational status of the isocitrate dehydrogenase (IDH) gene plays a key role in the treatment of glioma patients because it is known to affect energy metabolism pathways relevant to glioma. Physio-metabolic magnetic resonance imaging (MRI) enables the non-invasive analysis of oxygen metabolism and tissue hypoxia as well as associated neovascularization and microvascular architecture. However, evaluating such complex neuroimaging data requires computational support. Traditional machine learning algorithms and simple deep learning models were trained with radiomic features from clinical MRI (cMRI) or physio-metabolic MRI data. A total of 215 patients (first center: 166 participants + 16 participants for independent internal testing of the algorithms versus second site: 33 participants for independent external testing) were enrolled using two different physio-metabolic MRI protocols. The algorithms trained with physio-metabolic data demonstrated the best classification performance in independent internal testing: precision, 91.7%; accuracy, 87.5%; area under the receiver operating curve (AUROC), 0.979. In external testing, traditional machine learning models trained with cMRI data exhibited the best IDH classification results: precision, 84.9%; accuracy, 81.8%; and AUROC, 0.879. The poor performance for the physio-metabolic MRI approach appears to be explainable by site-dependent differences in data acquisition methodologies. The physio-metabolic MRI approach potentially supports reliable classification of IDH gene status in the presurgical stage of glioma patients. However, non-standardized protocols limit the level of evidence and underlie the need for a reproducible framework of data acquisition techniques. [ABSTRACT FROM AUTHOR]

Objective: The extent of resection and neurological outcome are important prognostic markers for overall survival in glioma patients. Confocal laser endomicroscopy is a tool to examine tissue without the need for fixation or staining. This study aims to analyze gliomas in confocal laser endomicroscopy and identify reliable diagnostic criteria for glial matter and glial tumors. Material and methods: One-hundred-and-five glioma specimens were analyzed using a 670-nm confocal laser endomicroscope and then processed into hematoxylin-eosin-stained frozen sections. All confocal images and frozen sections were evaluated for the following criteria: presence of tumor, cellularity, nuclear pleomorphism, changes of the extracellular glial matrix, microvascular proliferation, necrosis, and mitotic activity. Recurring characteristics were identified. Accuracy, sensitivity, specificity, and positive and negative predictive values were assessed for each feature. Results: All 125 specimens could be processed and successfully analyzed via confocal laser endomicroscopy. We found diagnostic criteria to identify white and grey matter and analyze cellularity, nuclear pleomorphism, changes in the glial matrix, vascularization, and necrosis in glial tumors. An accuracy of > 90.0 % was reached for grey matter, cellularity, and necrosis, > 80.0 % for white matter and nuclear pleomorphism, and > 70.0 % for microvascular proliferation and changes of the glial matrix. Mitotic activity could not be identified. Astroglial tumors showed significantly less nuclear pleomorphism in confocal laser endomicroscopy than oligodendroglial tumors (p < 0.001). Visualization of necrosis aids in the differentiation of low grade gliomas and high grade gliomas (p < 0.002). Conclusion: Autofluorescence-based confocal laser endomicroscopy proved not only useful in differentiation between tumor and brain tissue but also revealed useful clues to further characterize tissue without processing in a lab. Possible applications include the improvement of extent of resection and the safe harvest of representative tissue for histopathological and molecular genetic diagnostics. [ABSTRACT FROM AUTHOR]

Central nervous system tumors in pediatric patients represent the most frequent solid tumor type in this age group, especially ependymomas, which comprise 5% of childhood intracranial tumors, and occur mainly in the posterior fossa. The MEDLINE and ClinicalTrials databases were searched for studies on posterior fossa ependymomas, 64 studies met the search criteria. Symptoms include ataxia, vertigo, headache, vomiting, cranial nerve palsies, or papilledema, resulting from intracranial hypertension due to obstruction of CSF circulation. Imaging examination often reveals posterior fossa ependymomas in the fourth ventricle or cerebellopontine angle; they may extend through the foramina of Luschka, Magendie, and/or magnum. These tumors cause a significant mass effect, displacing rather than invading the hidbrain, and may involve vessels or cranial nerves, making surgical resection difficult. Various radiological features have been studied to distinguish between ependymomas and other histological types, as well as between ependymoma subtypes. The 2021 WHO classification of central nervous system tumors classifies ependymomas by location. Three types occur in the posterior fossa: subependymomas, PF-A, and PF-B. These are differentiated by the degree of DNA methylation and CpG islands, which can be assessed by immunohistochemical analysis with H3K27me3. The consensus on the treatment of posterior fossa ependymomas in children advocates the maximum possible surgical resection, followed by radiotherapy in patients >1 year. Chemotherapy remains controversial, with no survival gain. Recent studies suggest molecular subgroups as an independent prognostic factor in posterior fossa ependymomas. The therapeutic challenge of ependymomas requires new treatment options, based on new technologies and molecular discoveries. [ABSTRACT FROM AUTHOR]

Introduction: Glioblastoma multiforme is the most common and aggressive type of central nervous system tumor. We present a novel case of the challenges of dosing temozolomide in a patient with end stage renal disease on peritoneal hemodialysis with unpredictable clearance and toxicities. Case report: In this case, a 60-year-old male with a past medical history of hypertension and Stage V chronic kidney disease presented with worsening confusion and word-finding difficulty in the emergency department. Magnetic resonance imaging demonstrated a large intra-axial mass within the posterior left frontal lobe measuring 4.5 × 4.1 × 3.5 cm with irregularly, predominant peripheral tumoral enhancement. Management and outcome: The patient underwent a surgical resection which confirmed the diagnosis of glioblastoma (grade 4). The standard treatment for glioblastoma is 6 weeks of radiation therapy and daily temozolomide. Given his history of renal dysfunction and limited data on the safety of temozolomide in patients on hemodialysis (HD), the patient was administered dose-reduced temozolomide and closely monitored for toxicities. Temozolomide was successfully up-titrated to the full dose. Discussion: Renal replacement therapy is a life-saving treatment for end-stage kidney disease patients. A stepwise increase in the dosage of temozolomide did not increase the risk of toxicity with HD. There are no studies with patients on temozolomide and peritoneal dialysis. Our case transitioned to peritoneal dialysis from HD without significant toxicity from temozolomide. As a more substantial proportion of the population becomes dialysis-dependent in the coming years, we need further studies to understand the safety profiles of chemotherapeutic agents in this complex subset of patients. [ABSTRACT FROM AUTHOR]

The emerging field of connectomics has provided an improved understanding of the structural and functional organization of the human brain into large-scale brain networks. Recent studies have helped define the canonical neurological networks and outline how considering their presence may aid in surgical decision-making in brain tumor patients. Gliomas represent one of the most common types of brain tumor and often involve displacement and/or infiltration of neurological pathways, suggesting an opportunity to use connectomic maps to improve patient morbidity and mortality based on oncofunctional goals. This review aims to provide a working knowledge of important neurological networks, examine the use of networks in surgical planning, and describe the current literature discussing the impact of these networks on clinical outcomes in glioma resection. [ABSTRACT FROM AUTHOR]

Glioblastoma (formerly named glioblastoma multiforme) is the most common primary central nervous system tumor, representing 45% of all cases and 15% of all intracranial neoplasms [1]. Its typical radiologic findings and localization make it often a lesion easy to diagnose. In MRI it usually appears as an irregularly shaped cystic lesion with ring contrast enhancement in T1-weighted images, localized in subcortical white matter and deep gray matter nuclei of the cerebral hemispheres. It involves more frequently the frontotemporal region followed by parietal lobes [1]. Few articles in literature described cases of intraventricular glioblastomas, defining those as secondary ventricular tumors because of their probable origin primarily from cerebral tissue with consequent transependymal development [2, 3]. Atypical presentations of these tumors make it more difficult to clearly differentiate them from other lesions more commonly located in the ventricular system. We describe a case with a unique radiological presentation: an intraventricular glioblastoma lying entirely within the ventricular walls, involving all the ventricular system, without mass effect or nodular parenchymal lesions. [ABSTRACT FROM AUTHOR]

Background: Radiooncological scores are used to stratify patients for radiation therapy. We assessed their ability to predict overall survival (OS) in patients undergoing surgery for metastatic brain disease. Methods: We performed a post-hoc single-center analysis of 175 patients, prospectively enrolled in the MetastaSys study data. Score index of radiosurgery (SIR), graded prognostic assessment (GPA), and recursive partitioning analysis (RPA) were assessed. All scores consider age, systemic disease, and performance status prior to surgery. Furthermore, GPA and SIR include the number of intracranial lesions while SIR additionally requires metastatic lesion volume. Predictive values for case fatality at 1 year after surgery were compared among scoring systems. Results: All scores produced accurate reflections on OS after surgery (p ≤ 0.003). Median survival was 21–24 weeks in patients scored in the unfavorable cohorts, respectively. In cohorts with favorable scores, median survival ranged from 42 to 60 weeks. Favorable SIR was associated with a hazard ratio (HR) of 0.44 [0.29, 0.66] for death within 1 year. For GPA, the HR amounted to 0.44 [0.25, 0.75], while RPA had a HR of 0.30 [0.14, 0.63]. Overall test performance was highest for the SIR. Conclusions: All scores proved useful in predicting OS. Considering our data, we recommend using the SIR for preoperative prognostic evaluation and counseling. [ABSTRACT FROM AUTHOR]

Papaverine, a vasodilator approved for use by the U.S. Food and Drug Administration, has shown efficacy in treating vasospasm in cardiology, urology, and nephrology. The vasodilatory effect of papaverine is also hoped to protect the facial nerve from ischemic damage and nerve manipulation during vestibular schwannoma surgery. Our institution uses intracisternal papaverine irrigation during vestibular schwannoma resection to protect the facial nerve in patients with neuromonitoring changes. Our objective was to investigate the safety and facial nerve outcomes of intracisternal papaverine irrigation during vestibular schwannoma resection. We retrospectively reviewed patients who underwent resection of vestibular schwannoma at our institution between 2008 and 2021. Patients received papaverine if the intraoperative facial nerve stimulation threshold increased above 0.05 mA. Postoperative outcomes were compared with control patients who did not receive papaverine. A total of 283 cases were included in our analysis. Patients who received papaverine (n = 60) had lower immediate postoperative House-Brackmann (HB) grades than did control individuals (mean, 1.54 vs. 1.95; P = 0.029) and a lower likelihood of immediate postoperative HB grade >1 (odds ratio, 0.514; P = 0.039). At long-term follow-up, there was no significant difference in HB grade. Papaverine use was not associated with increased rates of perioperative complications (P = 0.24). The off-label use of intracisternal papaverine irrigation during vestibular schwannoma resection can certainly be used safely for select cases. It is associated with improved immediate postoperative facial nerve outcomes, similar long-term facial nerve outcomes, and no significant increase in complications. [ABSTRACT FROM AUTHOR]

Background: Disseminated diffuse midline glioma (DMG) is a devastating diagnosis. Molecular subtyping has increased our understanding of this tumor. Case: Here, we report the case of an 8-year-old girl who presented with symptoms of brainstem dysfunction and was found to have disseminated DMG with lesions in the pons, thalamus and bilateral temporal lobes. Molecular subtyping of the temporal lobe tumor tissue was consistent with H3 K27me3 loss and EZHIP overexpression, falling under the newly designated "H3 K27-altered" AQ5WHO subtype of DMG. Pathology from biopsy of the orbital lesion showed poorly differentiated rhabdoid-like disseminated tumor cells. The patient went on to develop lesions in the peritoneum, infratemporal fossa, and along the lumbosacral nerve roots. Conclusion: This unique case illustrates the aggressive behavior of H3 K27-altered tumors and their potential to metastasize. [ABSTRACT FROM AUTHOR]

Purpose: To investigate if quantitative contrast enhancement and iodine mapping of common brain tumor (BT) entities may correctly differentiate between tumor etiologies in standardized stereotactic CT protocols. Material and Methods: A retrospective monocentric study of 139 consecutive standardized dual-layer dual-energy CT (dlDECT) scans conducted prior to the stereotactic needle biopsy of untreated primary brain tumor lesions. Attenuation of contrast-enhancing BT was derived from polyenergetic images as well as spectral iodine density maps (IDM) and their contrast-to-noise-ratios (CNR) were determined using ROI measures in contrast-enhancing BT and healthy contralateral white matter. The measures were correlated to histopathology regarding tumor entity, isocitrate dehydrogenase (IDH) and MGMT mutation status. Results: The cohort included 52 female and 76 male patients, mean age of 59.4 (±17.1) years. Brain lymphomas showed the highest attenuation (IDM CNR 3.28 ± 1,23), significantly higher than glioblastoma (2.37 ± 1.55, p < 0.005) and metastases (1.95 ± 1.14, p < 0.02), while the differences between glioblastomas and metastases were not significant. These strongly enhancing lesions differed from oligodendroglioma and astrocytoma (Grade II and III) that showed IDM CNR in the range of 1.22–1.27 (±0.45–0.82). Conventional attenuation measurements in DLCT data performed equally or slightly superior to iodine density measurements. Conclusion: Quantitative attenuation and iodine density measurements of contrast-enhancing brain tumors are feasible imaging biomarkers for the discrimination of cerebral tumor lesions but not specifically for single tumor entities. CNR based on simple HU measurements performed equally or slightly superior to iodine quantification. [ABSTRACT FROM AUTHOR]

Leksell stereotactic system-based aspiration biopsy is a common procedure in the neurosurgical treatment of deep-seated or multiple brain lesions. This study aimed to evaluate the benefit of frameless biopsy using VarioGuide compared to frame-based biopsy using the Leksell stereotactic system (LSS). We analyzed all brain biopsies using VarioGuide or LSS at our neurooncological Department of Neurosurgery in the University Hospital of Bonn between January 2018 and August 2020. We analyzed demographic data, duration of surgery, size of lesion, localization, and early complications. Uni-variable analyses were carried out on data from both groups. In total, 109 biopsies were compared (40 VarioGuide vs. 69 LSS). Patients with VarioGuide were significant older (74 (62–80) years vs. 67 (57–76) years; p = 0.03) and had a shorter duration of general anesthesia (163 (138–194) min vs. 193 (167–215) min, p < 0.001). We found no significant differences in surgery duration (VarioGuide median 28 min (IQR 20–38); LSS: median 30 min (IQR 25–39); p = 0.1352) or in early complication rates (5% vs. 7%; p = 0.644). A slightly higher false negative biopsy rate was registered in the LSS group (3 vs. 1; p = 0.1347). The size of the lesions also did not differ significantly between the two groups (18.31 ± 26.35 cm3 vs. 12.63 ± 14.62; p = 0.15). Our data showed that biopsies performed using VarioGuide took significantly less time than LSS biopsies and did not differ in complication rates. Both systems offered a high degree of patient safety. [ABSTRACT FROM AUTHOR]

Introduction: Neurofibromatosis type 1 (NF-1) comprises a spectrum of malignant lesions. Central nervous system (cns) tumors, such as malignant gliomas, appear as predominant clinical manifestation. Malignant lymphomas constitute a rare entity in adults with NF-1, but there can be atypical presentations mimicking other brain tumors. Case presentation: We report the very unusual case of a 53-year-old Mexican female with history of NF-1, who developed a primary central nervous system lymphoma (pcnsl) as first neoplastic lesion. She initially presented sub-acute and progressive left-sided numbness and weakness, leading to hemiplegia. mri showed an heterogenous left central lobe lesion with surrounding edema. After lesion-centered craniectomy for surgical resection, pathology revealed lymphoid lineage cells. Immunohistochemical staining showed positivity of CD20, PAX-5, Ki-67, validating pcnsl diagnosis. 6-months follow-up mri showed no residual mass. Two months later patient recovered fully. Conclusion: pcnsl is a malignant serious neurologic condition with symptoms that mimic other brain tumors. Patients with NF-1 can initially present these lesions. Diagnosis should be considered within the NF-1 spectrum, and subsequently, a thorough study of this entity should be made, since pathophysiological mechanisms behind it are still unclear. Studies of prevalence and further guidelines are mandatory to critically appraise its medical and surgical management. [ABSTRACT FROM AUTHOR]

Summary: Background: A standardized approach for identifying and treating hypothalamic obesity (HO) in children with hypothalamic tumours is lacking. Objectives: To describe children with hypothalamic tumours at risk for obesity, assess outcomes of a novel HO clinical algorithm, and identify factors associated with weight gain. Methods: Retrospective analysis of youth with hypothalamic and suprasellar tumours, seen at a paediatric tertiary care centre from 2010 to 2020. Results: The study cohort (n = 130, 50% female, median age at diagnosis 5 [range 0–17]y) had a median duration of follow up of 5 (0.03–17)y. At last recorded body mass index (BMI) measurement, 34% had obesity, including 17% with severe obesity. Median onset of overweight and obesity after diagnosis was 6.2 (0.3–134) and 8.9 (0.7–65) months, respectively. After algorithm implementation (n = 13), the proportion that had an early dietitian visit (within 6 months) increased from 36% to 54%, (p = 0.498) and weight management referrals increased from 51% to 83% (p = 0.286). Higher BMI z‐score at diagnosis was associated with overweight and obesity development (p < 0.001). Conclusion: Patients with hypothalamic tumours commonly develop obesity. Use of a clinical algorithm may expedite recognition of HO. Further research is needed to identify predictors of weight gain and to develop effective treatment. [ABSTRACT FROM AUTHOR]

Sellar region is a rare localization for intracranial metastases. The diagnosis is frequently delayed as symptoms are generally non specific. Radiologic diagnosis may be difficult as these tumours present similiraities to other more frequent sellar tumours. There is still no consensus regarding therapeutic approach. Prognosis is related to several features. Pituitary metastases are rare tumors mainly diagnosed in patients with multiple metastatic lesions. Diagnosis is difficult as clinical symptoms are nonspecific. Treatment mainly aims to improve the quality of life. [ABSTRACT FROM AUTHOR]

Background: Brain tumor therapeutic responses can be quantified from magnetic resonance images (MRI) using 1‐ (1D) and 2‐dimensional (2D) linear and volumetric methods, but few studies in dogs compare these techniques. Hypotheses: Linear methods will be obtained faster, but have less agreement than volumetric measurements. Therapeutic response agreement will be highest with the total T2W tumor volumetric (TTV) method. Therapeutic response at 6‐weeks will correlate with overall survival (OS). Animals: Forty‐six dogs with intracranial gliomas. Methods: Prospective study. Three raters measured tumors using 1D and 2D linear, TTV, and contrast‐enhancing volumetric (CEV) techniques on 143 brain MRI to determine agreement between methods, define therapeutic responses, and assess relations with OS. Results: Raters performed 1D the fastest (2.9 ± 0.57 minutes) and CEV slowest (17.8 ± 6.2 minutes). Inter‐ and intraobserver agreements were excellent (intraclass correlations ≥.91) across methods. Correlations between linear (1D vs 2D; ρ >.91) and volumetric (TTV vs CEV; ρ >.73) methods were stronger than linear to volumetric comparisons (ρ range,.26‐.59). Incorporating clinical and imaging data resulted in fewer discordant therapeutic responses across methods. Dogs having partial tumor responses at 6 weeks had a lower death hazard than dogs with stable or progressive disease when assessed using 2D, CEV, and TTV (hazard ration 2.1; 95% confidence interval, 1.22‐3.63; P =.008). Conclusions and Clinical Importance: One‐dimensional, 2D, CEV, and TTV are comparable for determining therapeutic response. Given the simplicity, universal applicability, and superior performance of the TTV, we recommend its use to standardize glioma therapeutic response criteria. [ABSTRACT FROM AUTHOR]

Purpose: Overall survival of malignant brain tumour patients has significantly been increased over the last years. However, therapy remains palliative, and side effects should be balanced. Once terminal phase is entered, both patients and caregivers may find it hard to accept, and further therapies are demanded. But little is known about this highly sensitive period. Therefore, we analysed the last therapy decisions from the family caregiver's perspective. Would they support their beloved ones in the same way or would they now recommend a different therapy decision? Methods: Caregivers of deceased malignant brain tumour patients, treated at our neurooncological centre between 2011 and 2017, were included. We designed a questionnaire to analyse the impact of the last therapy decision (resection, chemotherapy, radiotherapy), focusing on probable repeat of the choice taken and general therapy satisfaction. Independent variables, for example "satisfaction with therapy", were analysed using linear regression analysis, the coefficient of determination R2 and the standardized regression coefficient β. The binary logistic regression analyses were taken to illustrate relationships with the dichotomously scaled outcome parameter "re-choice of therapy". Odds ratio analyses were used to determine the strength of a relationship between two characteristics. Results: Data from 102 caregivers (life partners (70.6%)) were analysed retrospectively. Each 40% of patients died in a hospice or at home (20% in a hospital). In 67.6% the last therapy was chemotherapy followed by radiotherapy (16.7%) and surgery (15.7%). A positive evaluation of the last therapy was significantly correlated to re-choosing of respective therapy (chemo-/radiotherapy: p = 0.000) and satisfaction with informed consent (p = 0.000). Satisfaction regarding interpersonal contact was significantly correlated to satisfaction with resection (p = 0.000) and chemotherapy (p = 0.000 27 caregivers (28.7%) felt overburdened with this situation). Conclusion: This analysis demonstrates a significant correlation between a positive relation of patient/caregiver/physician and the subjective perception of the latest therapy. It underlines the central role of caregivers, who should be involved in therapy discussions. Neurooncologists should be specially trained in communication and psycho-oncology. [ABSTRACT FROM AUTHOR]

High-grade gliomas (HGGs) are the commonest primary brain cancers. They are characterized by a pattern of aggressive growth and diffuse infiltration of the host brain that severely limits the efficacy of conventional treatments and patient outcomes, which remain generally poor. Recent work has described a suite of mechanisms via which HGGs interact, predominantly bidirectionally, with various cell types in the host brain including neurons, glial cells, immune cells, and vascular elements to drive tumor growth and invasion. These insights have the potential to inspire novel approaches to HGG therapy that are critically needed. This review explores HGG–host brain interactions and considers whether and how they might be exploited for therapeutic gain. [ABSTRACT FROM AUTHOR]

Olfactory disturbance is a common complication that occurs following the surgical resection of olfactory groove meningiomas (OGMs). There is little evidence on the best transcranial approach that minimizes rates of postoperative olfactory disturbance. The objective of this systematic review and meta-analysis is to compare smell outcomes after OGM resection in unilateral versus bilateral transcranial approaches. A systematic review of the literature and meta-analysis was conducted using PUBMED, SCOPUS, and EMBASE in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The primary endpoint was incidence of new olfactory disturbance defined as anosmia or hyposmia, or both. Patients were classified as undergoing either a unilateral or bilateral approach. Data on presence of new postoperative olfactory deficits were used to generate standardized mean differences and 95% confidence intervals. Ten studies met the inclusion criteria for quantitative analysis, comprising 342 patients. A total of 216 patients underwent unilateral approaches while 126 underwent resection via bilateral approach. In the unilateral approach cohort, 17.1% experienced new postoperative olfactory disturbance following resection, compared with 19.2% of patients in the bilateral approach cohort. Forest plot did not reveal any significant difference in the incidence of new olfactory disturbance following either unilateral or bilateral approaches. Our data suggest that there is no significant difference between the investigated transcranial approaches and postoperative olfactory disturbances. Accordingly, our study suggests that further investigation with introduced experimental control could provide more insight into the capabilities and drawbacks of each route in relation to olfactory outcomes. [ABSTRACT FROM AUTHOR]

Background: Paraneoplastic neurological syndromes (PNS) affecting the CNS (central nervous system) are rare, presenting in less than 1% of all those with cancer. The pathogenesis of paraneoplastic neurological syndromes is not fully understood, but it is presumed to result from an immune attack on the underlying malignancy. The presence of different types of onconeural antibodies may occur in different tumors and can lead to different clinical manifestations, making the early detection of cancers challenging. Aim: An evaluation of [18F]FDG PET/CT in neoplastic tumor detection in patients with paraneoplastic neurological syndromes having negative or unremarkable results of conventional radiological imaging. Methods: Among all patients diagnosed with paraneoplastic neurological syndromes in the Neurology Department in 2016–2020, 15 patients with unremarkable conventional radiological findings who underwent [18F]FDG PET/CT were included in the study. Results: [18F]FDG PET/CT enabled localization of suspected malignancy in 53% (8 of 15) of PNS cases with previous unremarkable conventional radiological findings. Conclusion: [18F]FDG PET/CT may be considered as a useful tool for neoplastic tumor detection in patients with paraneoplastic neurological syndromes, accelerating the diagnostic process and enabling faster initiation of appropriate treatment. [ABSTRACT FROM AUTHOR]

Introduction: The extent of meningioma resection is the most fundamental risk factor for recurrence, and exact knowledge of extent of resection is necessary for prognostication and for planning of adjuvant treatment. Currently used classifications are the EANO-grading and the Simpson grading. The former comprises radiological imaging with contrast-enhanced MRI and differentiation between "gross total removal" and "subtotal removal," while the latter comprises a five-tiered differentiation of the surgeon's impression of the extent of resection. The extent of resection of tumors is usually defined via analyses of resection margins but has until now not been implemented for meningiomas. PET/MRI imaging with 68Ga-DOTATOC allows more sensitive and specific imaging than MRI following surgery of meningiomas. Objective: To develop an objective grading system based on microscopic analyses of resection margins and sensitive radiological analyses to improve management of follow-up, adjuvant therapy, and prognostication of meningiomas. Based on the rationale of resection-margin analyses as gold standard and superior imaging performance of 68Ga DOTATOC PET, we propose "Copenhagen Grading" for meningiomas. Results: Copenhagen Grading was described for six pilot patients with examples of positive and negative findings on histopathology and DOTATOC PET scanning. The grading could be traceably implemented and parameters of grading appeared complementary. Copenhagen Grading is prospectively implemented as a clinical standard at Rigshospitalet, Copenhagen. Conclusion: Copenhagen Grading provided a comprehensive, logical, and reproducible definition of the extent of resection. It offers promise to be the most sensitive and specific imaging modality available for meningiomas. Clinical and cost-efficacy remain to be established during prospective implementation. [ABSTRACT FROM AUTHOR]

Purpose: Medulloblastoma is one of the most common malignant brain tumors in the pediatric population. Recent studies identified four distinct medulloblastoma subgroups with different molecular alterations and pathways, and natural courses and outcomes. To evaluate the results of surgical and medical treatments of patients with medulloblastoma and compare them among the medulloblastoma subgroups. Methods: The clinical and radiological features, medical and surgical management and treatment outcomes and their correlation with molecular subgroups of 58 patients treated for medulloblastoma in the last 20 years were evaluated. Results: Fifty-eight patients, of whom 35 were male and 23 were female, were evaluated. The median age was 6 years (range, 1–19 years). The most common symptoms were nausea and vomiting (60%). Forty-three percent of the patients had headache and 40% had ataxia. Previous pathology reports revealed that 43 (74%), eight (14%), five (8%), and two (3%) had classic, desmoplastic, desmoplastic/nodular, and anaplastic morphologies, respectively. After the subgroup analyses, five patients (12%) were attributed to the wingless subgroup (WNT) group; 14 (32.5%), to the sonic hedgehog subgroup (SHH) group; and 24 (56%), to the non-WNT non-SHH group. On the basis of immunohistochemical analysis results, 15 patients could not be attributed to any subgroups. The clinical risk groups (average vs high-risk) and age at diagnosis (≥ 3 years vs < 3 years of age) were significant for 5-year event free survival (86% vs 43%, p:0.011 and 59% vs 36%, p:0.039). There was no significant difference in survival or event free survival according to molecular subtypes in this cohort. Conclusion: In corporation of molecular features to the clinicopathologic classification leads to risk-adapted treatment. Although the molecular subgroups did not affect outcome significantly in this study, more studies with larger numbers of patients are needed to understand the tumor pathophysiology of medulloblastoma and design the future medical practice. [ABSTRACT FROM AUTHOR]

There has been a steady increase of vestibular schwannoma (VS) research in the body of literature. To delineate the most impactful works on VS, a bibliometric analysis is warranted. The Thomson Reuters Web of Sciences database was queried to identify all articles on VS published to June 2020. The articles were sorted in descending order of the number of citations. Titles and abstracts of the top 100 most-cited articles were screened to identify the research area, publication year, author, and country of publication. Our query yielded 6477 research publications. The 100 most-cited articles were cited 15804 times. The most productive decade was the 1990s (40% of the top 100 articles). Twenty-five journals contributed to all included articles. Journal of Neurosurgery contributed most of the articles (20%). Most common contributing country was the USA (60%). "Operative treatment" was the most common research topic (68%), followed by other aspects such as medical management (13%), epidemiology (12%), diagnosis (5%), or translational medicine (2%). The current analysis highlights the importance of the multimodal approach in the study and treatment of VS. While emphasizing the relevance of including highly cited articles in the current education of VS, our results point out the deficiency in certain research areas with high impact in other fields of neuro-oncology, such as translational medicine and molecular epigenetics. [ABSTRACT FROM AUTHOR]

Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens. [ABSTRACT FROM AUTHOR]

Purpose: The introduction of hypofractionated stereotactic radiosurgery (hSRS) extended the treatment modalities beyond the well-established single-fraction stereotactic radiosurgery and fractionated radiotherapy. Here, we report the efficacy and side effects of hSRS using Cyberknife® (CK-hSRS) for the treatment of patients with critical brain metastases (BM) and a very poor prognosis. We discuss our experience in light of current literature. Methods: All patients who underwent CK-hSRS over 3 years were retrospectively included. We applied a surface dose of 27 Gy in 3 fractions. Rates of local control (LC), systemic progression-free survival (PFS), and overall survival (OS) were estimated using Kaplan–Meier method. Treatment-related complications were rated using the Common Terminology Criteria for Adverse Events (CTCAE). Results: We analyzed 34 patients with 75 BM. 53% of the patients had a large tumor, tumor location was eloquent in 32%, and deep seated in 15%. 36% of tumors were recurrent after previous irradiation. The median Karnofsky Performance Status was 65%. The actuarial rates of LC at 3, 6, and 12 months were 98%, 98%, and 78.6%, respectively. Three, 6, and 12 months PFS was 38%, 32%, and 15%, and OS was 65%, 47%, and 28%, respectively. Median OS was significantly associated with higher KPS, which was the only significant factor for survival. Complications CTCAE grade 1–3 were observed in 12%. Conclusion: Our radiation schedule showed a reasonable treatment effectiveness and tolerance. Representing an optimal salvage treatment for critical BM in patients with a very poor prognosis and clinical performance state, CK-hSRS may close the gap between surgery, stereotactic radiosurgery, conventional radiotherapy, and palliative care. [ABSTRACT FROM AUTHOR]

Purpose: Psychosocial screening for glioma patients is challenging because many patients suffer from neurocognitive deficits, which may impair assessment. This study's aim was to exploratively develop three screening questions for unmet needs to prospectively be applicable in patient–doctor consultation. Methods: Patient interviews, a survey for health-care professionals and a weighted scoring procedure were developed for this study. Six main areas were defined according to main areas of validated questionnaires (psyche, cognition, body, role functioning, social support, unmet needs). Patients and health-care professionals rated the importance of these areas and corresponding items, patients additionally stated whether the issues addressed affected them. Results: A total of 50 patients were included, and 36 health-care professionals participated in the online survey. The three areas (psyche, body and cognition) considered to be most relevant by both, health-care professionals and patients, generated three screening questions. If the patient was affected by the issue addressed with a screening question, a subordinate question from that area that our patient sample considered most important could additionally be asked. The elaborated screening questions are the following: (1) main area psyche: "Has your mood worsened?", (2) main area body: "Do physical changes put a strain on you?", and (3) main area cognition: "Has your memory capacity worsened?" Conclusion: These questions represent a basis for further research regarding their application in neuro-oncological clinical routine. [ABSTRACT FROM AUTHOR]

Neuro-oncology is a rapidly evolving subspecialty that involves the management of patients with primary or metastatic central and peripheral nervous system neoplasms, as well as any other disorders or complications affecting the nervous system that result either directly or indirectly from central nervous system or systemic malignancies and related treatment. Neurologists serve a critical role in the multidisciplinary management of these complex patients. As leaders of the Child Neurology Society Special Interest Group in NeuroOncology, we propose ways to provide sufficient exposure, minimize knowledge gaps, and optimize training experiences in neuro-oncology for child neurology residency programs. [ABSTRACT FROM AUTHOR]

Background: During the latest decades, the hypothesis that the subjective experience of free will is determined by preconscious activity in the dominant dorsal medial frontal cortex (dMFC) has repeatedly challenged our commonly held concepts of moral responsibility. Aims of the study: To investigate whether dMFC activity determines the sense of free will and to investigate the effects of resections in this area on quality of life (QoL). Methods: A cohort of nine patients affected by transient declines in speech and movement skills after surgery involving the left dMFC answered questions about their post‐operative, subjective experiences of volition in relation to symptoms. In eight cases, resections were performed as part of glioma surgery, and in the ninth case, a meningioma adjacent to the dMFC was resected. In addition, a QoL questionnaire was administrated before and after surgery. Results: None of the patients perceived the transient disabilities related to surgery as associated with a loss or absence of volition. No declines in QoL were detected after surgery. Two QoL domains showed improved function (motor dysfunction and future uncertainty). Conclusions: The subjective sense of volition is not contingent on dMFC activity. Surgical resections of this area are not typically associated with declines in QoL. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence suggests that STK11 mutations may influence clinical outcome and response to immunotherapy in cancer.Materials and Methods: Next-generation targeted sequencing of STK11 mutation status in a large cohort of 188 meningiomas.Results: STK11 loss-of-function mutations were identified in 3.7% of meningiomas. STK11 mutations were found in both low- and high-grade lesions and samples from primary and recurrent disease. There was a 2.8-fold increased risk of death for patients whose meningioma harbored an STK11 mutation, after controlling for lesion grade and occurrence status. The median overall survival for patients with STK11-mutated meningiomas was 4.4 years compared with 16.8 years.Conclusion: These data identify recurrent STK11 mutations in a subset of meningiomas. Genotyping of STK11 is encouraged for meningioma patients undergoing immunotherapy-based therapy. [ABSTRACT FROM AUTHOR]

The standard first-line therapy for glioblastoma consists of maximal surgical resection, followed by concurrent chemoradiotherapy. Optimal management for older glioblastoma patients is unknown as they have not been extensively studied in clinical trials. We report data from a series of 156 consecutive glioblastoma patients treated at our institution from 2007 to 2017. Compared to glioblastoma patients aged 70 or less, the patients older than 70 were less likely to undergo surgical resection (34% vs. 64%; p = 0.0003), be treated with adjuvant chemotherapy (37% vs. 59%; p = 0.01) or radiation therapy (36% vs. 56%; p = 0.03). Disease-specific survival was significantly shorter in this age group (4.7 vs. 15.3 months; p = 0.002). Nonetheless, when older patients did undergo surgery or chemotherapy, the proportional improvement in cancer-specific survival was similar to the one recorded in younger patients, which is concordant with the findings of other published reports. A multidisciplinary input from neurosurgeons, medical and radiation oncologists, oncology pharmacists and geriatricians remain paramount for the optimal management of glioblastoma in patients older than 70. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma, IDH-wildtype is defined as a WHO CNS grade 4 glioma and constitutes the most common type of primary malignant cerebral tumor, that is a tumor arising from the cells of the central nervous system (CNS), as well as one of the most malignant tumors in humans reflecting its infiltrative nature and severity of clinical presentation. It accounts for approximately 50% of all primary malignant CNS neoplasms. Patients suffering from Glioblastoma often show a rapid decline in cognitive and physical capabilities underlining the tumors grave impact on both longevity as well as quality of life. Therapeutic options are currently limited to surgical resection, radiotherapy and chemotherapy with a mean survival at maximum therapy of just about 12 months, leaving researchers on a quest for maximizing efficacy of current treatment options on one hand while scouting for novel therapeutic remedies on the other.The objective of this paper is the evaluation of GBM patients clinical, imagistic and histopathological presentation and their surgical treatment in the Targu-Mures county hospital. Material and methods: This single-center study was conducted in a prospective manner over the period of one year (01.01.2023 -- 31.12.2023). All patients with suspected malignant glioma admitted to the Emergency County Hospital Targu-Mures to the department of neurosurgery were included in the study. Data was collected on patient demographics, clinical presentation at admission, tumor appearance on MRI, surgical approach and degree of resection, clinical outcome at discharge and tumor histopathology. Other examined factors were patient comorbidities, alcohol/tobacco/drug abuse, and laboratory data. Based on histopathological examination only patients with Glioblastoma IDH-Wildtype were included in the study, while all patients with other types of malignancy and lesions were excluded. Results: 22 patients were included in the study, 12 males and 10 females with a mean age of 60,36 years. Mean Tumor volume was 39,45cm^3, peritumoral edema volume was measured at a mean of 118,77cm^3 diameter and 8 patients (36%) presented significant midline shift > 5mm. The symptomatology was diverse with patients presenting with cephalgia, new-onset epileptic seizures, focal neurological deficits, alteration of personality, behavior or motivation amongst others. Decision to perform surgery was made in 21 patients (95%) with either surgical resection or stereotactic biopsy. Of the 16 cases scheduled for surgical resection in 15 (94%) GTR was achieved. 1 patient required reoperation in which GTR was achieved, amounting to successful GTR in 100% of patients. Clinical improvement was achieved in 18 cases (82%), worsening in 2 cases (9%) and no change in 2 cases (9%). Clinical improvement amongst patients treated with surgical resection was achieved in 100%. Conclusions: Statistical analysis of our results showed amongst others significantly improved outcomes of patients treated with surgical resection over those with biopsy or non-surgical treatment alone, underlining both the role of surgery in treatment of malignant gliomas as well as the surgical excellence of the neurosurgery department of the Emergency County hospital Targu-Mures under leadership of Prof. Dr. Adrian Balasa. [ABSTRACT FROM AUTHOR]

Preoperative non-invasive mapping of motor function with navigated transcranial magnetic stimulation (nTMS) has become a widely used diagnostic procedure. Determination of the patient-individual resting motor threshold (rMT) is of great importance to achieve reliable results when conducting nTMS motor mapping. Factors which contribute to differences in rMT of brain tumor patients have not been fully investigated. We included adult patients with all types of de novo and recurrent intracranial lesions, suspicious for intra-axial brain tumors. The outcome measure was the rMT of the upper extremity, defined as the stimulation intensity eliciting motor evoked potentials with amplitudes greater than 50µV in 50 % of applied stimulations. Eighty nTMS examinations in 75 patients (37.5 % female) aged 57.9 ± 14.9 years were evaluated. In non-parametric testing, rMT values were higher in patients with upper extremity paresis (p = 0.024) and lower in patients with high grade gliomas (HGG) (p = 0.001). rMT inversely correlated with patient age (r s =-0.28, p = 0.013) and edema volume (r s =-0.28, p = 0.012) In regression analysis, infiltration of the precentral gyrus (p <0.001) increased rMT values. Values of rMT were reduced in high grade gliomas (p <0.001), in patients taking Levetiracetam (p = 0.019) and if perilesional edema infiltrated motor eloquent brain (p <0.001). Subgroup analyses of glioma patients revealed similar results. Values of rMT did not differ between hand and forearm muscles. Most factors confounding rMT in our study were specific to the lesion. These factors contributed to the variability in cortical excitability and must be considered in clinical work with nTMS to achieve reliable results with nTMS motor mapping. [ABSTRACT FROM AUTHOR]

[Display omitted] • Malignant brain tumours grow and propagate in response to neural signalling. • Glutamatergic signalling between neurons and tumour cells promotes tumour growth. • Pharmaceuticals can target such abnormal neural signalling and glutamate activity. • Brain stimulation and electrical field therapy can attenuate glutamatergic signalling. • These may represent novel therapeutic approaches in brain tumours. High grade gliomas carry a poor prognosis despite aggressive surgical and adjuvant approaches including chemoradiotherapy. Recent studies have demonstrated a mitogenic association between neuronal electrical activity and glioma growth involving the PI3K-mTOR pathway. As the predominant excitatory neurotransmitter of the brain, glutamate signalling in particular has been shown to promote glioma invasion and growth. The concept of the neurogliomal synapse has been established whereby glutamatergic receptors on glioma cells have been shown to promote tumour propagation. Targeting glutamatergic signalling is therefore a potential treatment option in glioma. Antiepileptic medications decrease excess neuronal electrical activity and some may possess anti-glutamate effects. Although antiepileptic medications continue to be investigated for an anti-glioma effect, good quality randomised trial evidence is lacking. Other pharmacological strategies that downregulate glutamatergic signalling include riluzole, memantine and anaesthetic agents. Neuromodulatory interventions possessing potential anti-glutamate activity include deep brain stimulation and vagus nerve stimulation – this contributes to the anti-seizure efficacy of the latter and the possible neuroprotective effect of the former. A possible role of neuromodulation as a novel anti-glioma modality has previously been proposed and that hypothesis is extended to include these modalities. Similarly, the significant survival benefit in glioblastoma attributable to alternating electrical fields (Tumour Treating Fields) may be a result of disruption to neurogliomal signalling. Further studies exploring excitatory neurotransmission and glutamatergic signalling and their role in glioma origin, growth and propagation are therefore warranted. [ABSTRACT FROM AUTHOR]

The article present a case study of a 77-year-old woman with multiple myeloma who developed cranial polyneuropathy involving the central nervous system (CNS). The topics include the rare occurrence of CNS involvement in multiple myeloma patients, the poor prognosis associated with it, and the potential use of radiation therapy and immunomodulatory drugs for symptom palliation.

Background: Fear of progression (FoP) is frequent in patients with cancer and of high clinical relevance. Despite the often devastating prognosis of brain cancer, FoP has not yet been assessed in neurooncological patients.Objective: The aim of this study was thus the assessment of FoP and its clinical correlates.Methods: In an ambulatory setting, 42 patients with a primary brain tumour completed the Fear of Progression questionnaire FoP-Q-12. Clinical correlates of FoP were assessed via a variety of measures, including patients' physical state (Karnofsky Performance Status, KPS), cancer-related psychosocial distress (Distress Thermometer, DT), anxiety (General Anxiety Disorder Scale, GAD-7), depression (Patient Health Questionnaire, PHQ-9), Quality of Life (Short Form Health Survey, SF-8), and unmet supportive care needs (Supportive Care Needs Survey, SCNS).Results: Eighteen patients (42%) suffered from high FoP (i.e. scored ≥ 34 in the FoP-Q-12). According to the 12 items of the FoP-Q-12, the greatest fears were worrying about what would happen to their family and being afraid of severe medical treatments. No sociodemographic variables (e.g. age, gender) or medical tumour characteristics (e.g. tumour malignancy, first or recurrent tumour) were related to FoP. Patients with more severe physical symptoms reported higher FoP. Patients with higher FoP were more anxious, more depressed, reported lower Quality of Life, and suffered from more unmet supportive care needs.Conclusion: Our results demonstrate that FoP is frequent and of high clinical relevance for neurooncological patients. Its assessment is not sufficiently covered by instruments for assessment of other areas of psychological morbidity (e.g. general anxiety). Moreover, FoP cannot be predicted by objective characteristics of the patients and disease. Thus, the routine screening for FoP is recommended in neurooncological patients. Clinicians should bear in mind that patients with high FoP are likely to suffer from high emotional distress and unmet supportive care needs and initiate treatment accordingly. [ABSTRACT FROM AUTHOR]

Differentiation of cancer cells entails the reversion of phenotype from malignant to the original. The conversion to cell type characteristic for another tissue is named transdifferentiation. Differentiation/transdifferentiation of malignant cells in high grade tumor mass could serve as a nonaggressive approach that potentially limits tumor progression and augments chemosensitivity. While this therapeutic strategy is already being used for treatment of hematological cancers, its feasibility for solid malignancies is still debated. We will presently discuss the natural compounds that show these properties, with focus on anthraquinones from Aloe vera , Senna, Rheum sp. and hop derived prenylflavonoids. [ABSTRACT FROM AUTHOR]

Background: Cancer research has made great progress in the recent years. With the increasing number of options in diagnosis and therapy the implementation of tumorboards (TUBs) has become standard procedure in the treatment of cancer patients. Adherence tests on tumor board decisions are intended to enable quality assurance and enhancement for work in tumor boards in order to continuously optimize treatment options for cancer patients.Methods: Subject of this study was the adherence of the recommendations made in three of 14 tumorboards, which take place weekly in the Center for Integrated Oncology (CIO) at the University Hospital Bonn. In total, therapy recommendations of 3815 patient cases were checked on their implementation. A classification into four groups has been made according to the degree of implementation. A second classification followed regarding the reasons for differences between the recommendation and the therapy which the patient actually received.Results: The study showed that 80.1% of all recommendations in the three TUBs were implemented. 8.3% of all recommendations showed a deviance. Most important reasons for the deviances were patient wish (36.5%), patient death (26%) and doctoral decision, due to the patient's comorbidities or side effects of the treatment (24.1%).Interestingly, deviance in all three tumor boards in total significantly decreased over time.Conclusions: Aim of the study was to clarify the use of tumor boards and find approaches to make them more efficient. Based on the results efficiency might be optimized by increased consideration of patients` preferences, improved presentation of patient-related data, more detailed documentation and further structuring of the tumor board meetings. [ABSTRACT FROM AUTHOR]

World human population is getting older and according to this, the incidence- prevalance of the diseases in this age group is increasing. Neurooncological diseases, especially seen in this age group are metastasis and glioblastoma. Comorbidities, therapy-related side effects and complications of the treatment modalities make the management difficult, and also increase the ratio of mobridity/ mortality. It is important to evaluate the problems in multidisciplinary process, to choose the best treatment modality without effecting the quality of life and functional independence [ABSTRACT FROM AUTHOR]

Background: A growing body of clinical data highlights the prognostic importance of achieving gross total resection (GTR) in patients with glioblastoma. The aim of this study was to determine nationwide practice and attitudes towards achieving GTR and dealing with residual enhancing disease. Methods: The study was in 2 parts: an electronic questionnaire sent to United Kingdom neuro-oncology surgeons to assess surgical practice followed by a 3-month prospective, multicenter observational study of current neurosurgical oncology practice. Results: Twenty-seven surgeons representing 22 neurosurgical units completed the questionnaire. Prospective data were collected for 113 patients from 15 neurosurgical units. GTR was deemed to be achieved at time of surgery in 82% (91/111) of cases, but in only 45% (36/80) on postoperative MRI. Residual enhancing disease was deemed operable in 16.3% (13/80) of cases, however, no patient underwent early repeat surgery for residual enhancing disease. The most commonly cited reason (38.5%, 5/13) was perceived lack of clinical benefit. Conclusion: There is a subset of patients for whom GTR is thought possible, but not achieved at surgery. For these patients, early repeat resection may improve overall survival. Further prospective surgical research is required to better define the prognostic implications of GTR for residual enhancing disease and examine the potential benefit of this early re-intervention. [ABSTRACT FROM AUTHOR]

Among childhood cancer survivors, increased stroke risk after cranial radiation therapy may be caused by radiation-induced arteriopathy, but limited data exist to support this hypothesis. Herein, we assess the timing and presence of cerebral arteriopathy identified by magnetic resonance angiography (MRA) after cranial radiation therapy in childhood brain tumor survivors. In a cohort of 115 pediatric brain tumor survivors, we performed chart abstraction and prospective annual follow-up to assess the presence of large vessel cerebral arteriopathy by MRA. We identified 10 patients with cerebral arteriopathy. The cumulative incidence of arteriopathy 5 years post–cranial radiation therapy was 5.4% (CI 0.6%-10%) and 10 years was 16% (CI 4.6%-26%). One patient had an arterial ischemic stroke 2.4 years post–cranial radiation therapy in the distribution of a radiation-induced stenotic artery. We conclude that large vessel arteriopathies can occur within a few years of cranial radiation therapy and can become apparent on MRA in under a year. [ABSTRACT FROM AUTHOR]

Background: Postoperative ischemia is a frequent phenomenon in patients with brain tumors and is associated with postoperative neurological deficits and impaired overall survival. Particularly in the field of cardiac and vascular surgery, the application of a brief ischemic stimulus not only in the target organ but also in remote tissues can prevent subsequent ischemic damage. We hypothesized that remote ischemic preconditioning (rIPC) in patients with brain tumors undergoing elective surgical resection reduces the incidence of postoperative ischemic tissue damage and its consequences.Methods: Sixty patients were randomly assigned to two groups, with 1:1 allocation, stratified by tumor type (glioma or metastasis) and previous treatment with radiotherapy. rIPC was induced by inflating a blood pressure cuff placed on the upper arm three times for 5 min at 200 mmHg in the treatment group after induction of anesthesia. Between the cycles, the blood pressure cuff was released to allow reperfusion. In the control group no preconditioning was performed. Early postoperative magnetic resonance images (within 72 h after surgery) were evaluated by a neuroradiologist blinded to randomization for the presence of ischemia and its volume.Results: Fifty-eight of the 60 patients were assessed for occurrence of postoperative ischemia. Of these 58 patients, 44 had new postoperative ischemic lesions. The incidence of new postoperative ischemic lesions was significantly higher in the control group (27/31) than in the rIPC group (17/27) (p = 0.03). The median infarct volume was 0.36 cm3 (interquartile range (IR): 0.0-2.35) in the rIPC group compared with 1.30 cm3 (IR: 0.29-3.66) in the control group (p = 0.09).Conclusions: Application of rIPC was associated with reduced incidence of postoperative ischemic tissue damage in patients undergoing elective brain tumor surgery. This is the first study indicating a benefit of rIPC in brain tumor surgery.Trial Registration: German Clinical Trials Register, DRKS00010409 . Retrospectively registered on 13 October 2016. [ABSTRACT FROM AUTHOR]

This study evaluates the extravasation pathways of circulating macromolecules in a rat glioma model (RG2) which was observed by both magnetic resonance imaging using ultrasmall superparamagnetic iron oxide and electron microscopy. Although magnetic resonance imaging signal enhancement was observed as soon as 10 min after injection (9.4% 2 h after injection), electron microscopy showed that endothelial cells were still tightly sealed. However, circulating immunoglobulin G and ultrasmall superparamagnetic iron oxide were found in large membrane compartments of endothelial cells, in the basal lamina (7.4±1.2 gold particles/μm² in the tumor versus 0.38±0.17 in healthy tissue, p=1.4.10-5) and between tumoral cells. Altogether, this strongly suggests an active transport mediated by macropinocytosis. To challenge this transport mechanism, additional rats were treated with amiloride, an inhibitor of macropinocytosis, leading to a reduction of membrane protrusions (66%) and of macropinosomes. Amiloride however also opened tumoral tight junctions allowing a larger extravasation of ultrasmall superparamagnetic iron oxide (magnetic resonance imaging signal enhancement of 35.7% 2 h after injection). Altogether, these results suggest that ultrasmall superparamagnetic iron oxide and immunoglobulin G in the RG2 glioma model follow an active extravasation pathway mediated by a macropinocytosis process. Amiloride also appears as a potential strategy to facilitate the extravasation of chemotherapeutic drugs in glioma. [ABSTRACT FROM AUTHOR]

We report a case of isolated myxopapillary ependymoma (MPE) of the fourth ventricle. This is the thirteenth reported case of primary intracranial MPE and the fourth reported case of MPE originating from the fourth ventricle. We suggest that exhaustive clinical and radiological investigation of a spinal ependymoma must be undertaken in all cases of intracranial ependymoma. [ABSTRACT FROM AUTHOR]

Glioblastoma is the most common and most aggressive primary brain tumour. Standard of care consists of surgical resection followed by radiotherapy and concomitant and maintenance temozolomide (temozolomide/radiotherapy→temozolomide). Corticosteroids are commonly used perioperatively to control cerebral oedema and are frequently continued throughout subsequent treatment, notably radiotherapy, for amelioration of side effects. The effects of corticosteroids such as dexamethasone on cell growth in glioma models and on patient survival have remained controversial. We performed a retrospective analysis of glioblastoma patient cohorts to determine the prognostic role of steroid administration. A disease-relevant mouse model of glioblastoma was used to characterize the effects of dexamethasone on tumour cell proliferation and death, and to identify gene signatures associated with these effects. A murine anti-VEGFA antibody was used in parallel as an alternative for oedema control. We applied the dexamethasone-induced gene signature to The Cancer Genome Atlas glioblastoma dataset to explore the association of dexamethasone exposure with outcome. Mouse experiments were used to validate the effects of dexamethasone on survival in vivo Retrospective clinical analyses identified corticosteroid use during radiotherapy as an independent indicator of shorter survival in three independent patient cohorts. A dexamethasone-associated gene expression signature correlated with shorter survival in The Cancer Genome Atlas patient dataset. In glioma-bearing mice, dexamethasone pretreatment decreased tumour cell proliferation without affecting tumour cell viability, but reduced survival when combined with radiotherapy. Conversely, anti-VEGFA antibody decreased proliferation and increased tumour cell death, but did not affect survival when combined with radiotherapy. Clinical and mouse experimental data suggest that corticosteroids may decrease the effectiveness of treatment and shorten survival in glioblastoma. Dexamethasone-induced anti-proliferative effects may confer protection from radiotherapy- and chemotherapy-induced genotoxic stress. This study highlights the importance of identifying alternative agents such as vascular endothelial growth factor antagonists for managing oedema in glioblastoma patients. Beyond the established adverse effect profile of protracted corticosteroid use, this analysis substantiates the request for prudent and restricted use of corticosteroids in glioblastoma. [ABSTRACT FROM AUTHOR]

SEE HOHLFELD AND SCHULZE-KOOPS DOI101093/BRAIN/AWW053 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Inclusion body myositis and T cell large granular lymphocytic leukaemia are rare diseases involving pathogenic cytotoxic CD8+ T cells. After encountering four patients with both disorders, we prospectively screened 38 patients with inclusion body myositis for the presence of expanded large granular lymphocyte populations by standard clinical laboratory methods (flow cytometry, examination of blood smears, and T cell receptor gene rearrangements), and performed muscle immunohistochemistry for CD8, CD57, and TIA1. Most (22/38; 58%) patients with inclusion body myositis had aberrant populations of large granular lymphocytes in their blood meeting standard diagnostic criteria for T cell large granular lymphocytic leukaemia. These T cell populations were clonal in 20/20 patients and stably present on follow-up testing in 15 patients a median of 350 days later. T cell aberrant loss of CD5 or gain of expression of CD16 and CD94 were common (19/42, 45%). In comparison, 2/15 (14%) age-matched patients with dermatomyositis, polymyositis, or necrotizing myopathy, and 0/20 (0%) age-matched healthy subjects had large granular lymphocyte expansions, with none of these patients having T cell aberrant expression of CD5, CD16 or CD94. Reduced blood CD4/CD8 ratio, increased blood CD8 count, and lymphocytosis were additional biomarkers highly correlated with flow cytometry-measured large granular lymphocyte expansions. Cross-sectional data suggested more aggressive disease in patients with such expansions than without. Muscle immunohistochemistry demonstrated invasion of large granular lymphocytes into muscle in 15/15 inclusion body myositis patients but in only 1/28 patients with dermatomyositis or polymyositis. The extent of CD8+ and CD57+ cells in inclusion body myositis muscle correlated with the size of blood large granular lymphocyte populations. Myofibre-invading cells expressed CD57, a marker of persistent T cell exposure to antigen and T cell aggressiveness. In many patients with inclusion body myositis, the autoimmune T cell expansion has evolved into a neoplastic-like or overtly neoplastic disorder, perhaps contributing to its relative refractoriness to immune-directed therapies previously reported. [ABSTRACT FROM AUTHOR]

Intramedullary tumors of the spinal cord account for 2%–4% of all central nervous system tumors. Surgical resection with intraoperative neuromonitoring, although challenging, remains the mainstay of treatment with the goal to prevent neurologic decline. We present a case of an unusual anaplastic glioma of the thoracic spinal cord in a 42-year-old male that spanned 7 vertebral levels and could not be definitively characterized using the 2021 World Health Organization Classification of Central Nervous System Tumors. [ABSTRACT FROM AUTHOR]

This case report describes the clinical, histopathological and immunohistochemical findings in two dogs with myelopathy associated with metastasis of follicular-compact thyroid carcinoma. Microscopically, both primary neoplasms were characterized by polygonal cells arranged in follicles (occasionally filled with eosinophilic colloid-like material) or in sheets. The neoplastic cells had a moderately eosinophilic cytoplasm and there was moderate anisokaryosis and anisocytosis. Additionally, the neoplastic cells were positive for thyroglobulin on immunohistochemistry, confirming the follicular origin of both tumors. This is a very uncommon presentation of this pathological condition. [ABSTRACT FROM AUTHOR]