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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]

Purpose: To benchmark palliative care practices in neurooncology centers across Germany, evaluating the variability in palliative care integration, timing, and involvement in tumor board discussions. This study aims to identify gaps in care and contribute to the discourse on optimal palliative care strategies. Methods: A survey targeting both German Cancer Society-certified and non-certified university neurooncology centers was conducted to explore palliative care frameworks and practices for neurooncological patients. The survey included questions on palliative care department availability, involvement in tumor boards, timing of palliative care integration, and use of standardized screening tools for assessing palliative burden and psycho-oncological distress. Results: Of 57 centers contacted, 46 responded (81% response rate). Results indicate a dedicated palliative care department in 76.1% of centers, with palliative specialists participating in tumor board discussions at 34.8% of centers. Variability was noted in the initiation of palliative care, with early integration at the diagnosis stage in only 30.4% of centers. The survey highlighted a significant lack of standardized spiritual care assessments and minimal use of advanced care planning. Discrepancies were observed in the documentation and treatment of palliative care symptoms and social complaints, underscoring the need for comprehensive care approaches. Conclusion: The study highlights a diverse landscape of palliative care provision within German neurooncology centers, underscoring the need for more standardized practices and early integration of palliative care. It suggests the necessity for standardized protocols and guidelines to enhance palliative care's quality and uniformity, ultimately improving patient-centered care in neurooncology. [ABSTRACT FROM AUTHOR]

The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, established new approaches to both CNS tumor nomenclature and grading, emphasizing the importance of integrated diagnoses and layered reports. This edition increased the role of molecular diagnostics in CNS tumor classification while still relying on other established approaches such as histology and immunohistochemistry. Moreover, it introduced new tumor types and subtypes based on novel diagnostic technologies such as DNA methylome profiling. Over the past decade, molecular techniques identified numerous key genetic alterations in CSN tumors, with important implications regarding the understanding of pathogenesis but also for prognosis and the development and application of effective molecularly targeted therapies. This review summarizes the major changes in the 2021 fifth edition classification of pediatric CNS tumors, highlighting for each entity the molecular alterations and other information that are relevant for diagnostic, prognostic, or therapeutic purposes and that patients' and oncologists' need from a pathology report. [ABSTRACT FROM AUTHOR]

As in previous years, including 2023, a major focus in the neurooncological area of neuropathology was put on more precise and constantly faster diagnostic procedures, even reaching the level of ultra-fast intraoperative diagnostics based on methylation profiling. Neuropathological diagnostic precision and clinical follow-up treatment has been further increased by combining DNA methylation profiling with targeted panel sequencing. A few new, molecularly defined tumor subtypes have been proposed, among others, a glioneuronal tumor with ATRX alteration, kinase fusion and anaplastic features (in its abbreviated form named GTAKA) and the de novo replication repair deficient glioblastoma, IDH-wildtype both having either distinct prognostic or therapeutic implications. Regarding the understanding of brain tumor development and progression, several novel mechanisms have been presented which might also be considered as treatment targets in the future, such as a) autonomous rhythmical Ca2+ oscillations in interconnected glioma cell networks driving tumor growth; b) transfer of mitochondria from normal astrocytes to glioma cells enhancing proliferation and self-renewal; c) brain endothelial cell remodeling upon matrix-metalloprotease 9 secretion by tumor cells metastasizing into the CNS and d) anti-tumor activity of microglia in CNS metastasis of breast cancer. Finally, in contrast to previous years, several very promising neurooncological treatment studies have been conducted, focusing on specific targets such as H3K27M or IDH1/2 mutations for which a proper neuropathological assessment is key. The continuous translation of potential new treatment targets using faster and precise diagnostic procedures will further pave the way for better individualized clinical care of neurooncological patients.

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]

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

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]

The review begins with an overview of the fundamental principles/physics underlying light, fluorescence, and other light-matter interactions in biological tissues. It then focuses on 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence spectroscopy methods used in neurosurgery (e.g., intensity, time-resolved) and in so doing, describe their specific features (e.g., hardware requirements, main processing methods) as well as their strengths and limitations. Finally, we review current clinical applications and future directions of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence spectroscopy in neurosurgery. [ABSTRACT FROM AUTHOR]

• General anaesthesia techniques in cancer surgery may influence operative outcomes. • Total intravenous anaesthesia (TIVA) is associated with reduction in operative time in glioblastoma surgery as compared with inhalational anaesthesia (IA). • We found no difference in overall survival between patients with glioblastoma receiving TIVA versus IA. Total intravenous anaesthesia (TIVA) is emerging as a preferred neuroanaesthetic agent compared with inhalational anaesthetic (IA) agents. We asked if TIVA with propofol and remifentanil was associated with shorter operative times compared to IA using sevoflurane in brain tumour surgery under GA. We performed a retrospective analysis of all patients undergoing surgery for glioblastoma (GBM). We assessed choice of GA agent (TIVA or IA) with total time patient was under GA (anaesthetic time), operative time and time taken to recover fully from GA (recovery time). Over a two year period 263 patients underwent surgery under GA for their GBM including 188 craniotomy operations, 63 burr hole biopsy procedures and 12 open biopsy procedures. Of these, 79 operations took place under TIVA and 184 operations under IA. TIVA was associated with significantly reduced mean operative time including time taken to wake up in theatre (104 min with TIVA, 129 min with IA; p = 0.02). TIVA was also associated with trends toward shorter mean recovery time (118 min, versus 135 min with IA; p = 0.08) and shorter mean anaesthetic time (163 min, versus 181 min with IA; p = 0.07). There was no difference between TIVA and IA groups as regards duration of inpatient stay, readmission rates, complications or survival. TIVA with propofol and remifentanil may reduce anaesthetic, operative and recovery times in patients undergoing surgery for their GBM. These findings may be attributable to favourable effects on intracranial pressure and cerebral perfusion, as well as rapid recovery from GA. In addition to clinical advantages, there may be financial and logistical benefits. [ABSTRACT FROM AUTHOR]

Composite pleomorphic xanthoastrocytoma-ganglioglioma (PXA-GG) is an extremely rare central nervous system neoplasm with 2 distinct but intermingled components. Whether this tumor represents a "collision tumor" of separate neoplasms or a monoclonal neoplasm with divergent evolution is poorly understood. Clinicopathologic studies and capture-based next generation sequencing were performed on extracted DNA from all available PXA-GG at 2 medical centers. Five PXA-GG were diagnosed in 1 male and 4 female patients ranging from 13 to 25 years in age. Four arose within the cerebral hemispheres; 1 presented in the cerebellar vermis. DNA was sufficient for analysis in 4 PXA components and 3 GG components. Four paired PXA and GG components harbored BRAF p.V600E hotspot mutations. The 4 sequenced PXA components demonstrated CDKN2A homozygous deletion by sequencing with loss of p16 (protein product of CDKN2A) expression by immunohistochemistry, which was intact in all assessed GG components. The PXA components also demonstrated more frequent copy number alterations relative to paired GG components. In one PXA-GG, shared chromosomal copy number alterations were identified in both components. Our findings support divergent evolution of the PXA and GG components from a common BRAF p.V600E-mutant precursor lesion, with additional acquisition of CDKN2A homozygous deletion in the PXA component as is typically seen in conventional PXA.

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]

• Novel technical application in brain metastasis surgery. • First report on intraoperative radiotherapy in cerebellar metastasis. • Technical details with illustrative cases on intraoperative radiotherapy. In order to improve surgical outcome and accelerate the adjuvant oncologic therapy, intraoperative Radiotherapy (IORT) has become a treatment option in oncologic surgery for various diseases including glioma and brain metastasis (BM). BMs are often located in the cranial posterior fossa (PF) requiring specific surgical considerations due to its complex anatomy. Up until now, data on IORT for BMs is limited and detailed description in the use of IORT for lesions in the PF is lacking. Our aim is to provide more insight into this emerging treatment strategy. We performed a retrospective analysis of patients receiving surgery for BMs and undergoing IORT at our institution. Each patient was discussed at the interdisciplinary tumor board decision before the intervention. Patient characteristics, functional status (Karnofsky Performance Score, KPS) before and after surgery, disease (recursive partitioning analysis, lesion size) and operative parameters were analyzed. Adverse events (AE) were recorded up until 30 days after the intervention and rated according to the Clavien Dindo Rating scale. Nine patients (5 female) were included. None underwent prior radiotherapy (RT). Mean age was 66 ± 11 years. Preoperative median KPS was 80%. Mean BM diameter was 3.2 ± 0.9 cm. There was no statistically significant deterioration of the functional status after the intervention. Two patients experienced AEs with both of them needing revision surgery. Surgery for BMs with IORT in the PF seems safe and feasible. Further studies are needed to evaluate the influence of IORT on long-term outcome after BM surgery. [ABSTRACT FROM AUTHOR]

BackgroundBrain metastases (BM) are a common and challenging issue, with their incidence on the rise due to advancements in systemic therapies and increased patient survival. Most patients present with single BM, some of them without any further extracranial metastasis (i.e., solitary BM). The significance of postoperative intracranial tumor volume in the treatment of singular and solitary BM is still debated.ObjectiveThis study aimed to determine the impact of resection and postoperative tumor burden on overall survival (OS) in patients with single BM.MethodsPatients with surgically treated single BM between 04/2007-01/2020 were retrospectively included. Residual tumor burden (RTB) was determined by manual segmentation of early postoperative brain MRI (72 h). Survival analyses were performed using Kaplan-Meier estimates for univariate analysis and Cox regression proportional hazards model for multivariate analysis, using preoperative Karnofsky performance status scale (KPSS), age, sex, RTB, incomplete resection and singular/solitary BM as covariates.Results340 patients were included, median age 64 years (54-71). 119 patients (35%) had solitary BM, 221 (65%) singular BM. Complete resection (RTB=0) was achieved in 73%, median preoperative tumor burden was 11.2 cm3 (5-25), and RTB 0 cm3 (0-0.2). Median OS of patients with singular BM was 13 months (4-33) vs 20 months (5-92) for solitary BM; p=0.062. Multivariate analysis revealed singular BM as independent risk factor for poorer OS: HR 1.840 (1.202-2.817), p=0.005. Complete vs. incomplete resection showed no significant OS difference (13 vs. 13 months, p=0.737). When focusing on solitary BM, complete resection led to a longer OS than incomplete resection (21 vs. 8 months), without statistical significance(p=0.250). Achieving RTB=0 resulted in higher OS for patients with solitary BM compared to singular BM (21 vs. 12 months, p=0.027). Patients who received postoperative radiotherapy (RT) had significantly longer OS compared to those without it (14 vs. 4 months, p

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.

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

Multiple myeloma (MM) is a malignant immunoproliferative disease involving plasma cells, leading to their malignant proliferation and the production of monoclonal paraproteins. Intracranial tumor spread in MM is very rare. This is a unique and infrequent localization, which makes it difficult to diagnose the disease. We report a rare case of treatment of a patient with MM intracranial spread, whose disease was presumably in remission and recurred as an intracranial plasmacytoma with a clinical picture of acute cerebrovascular accident. Surgical intervention was performed to remove the tumor, a histopathological analysis of the removed tissue was carried out. Even with early diagnosis, the prognosis remains bleak, with median survival rates of 3 to 6 months. However, aggressive multimodal treatment can prolong life by months.

Supratentorial glioblastoma is a common primary intracranial tumor in adults. High-grade glioma in cerebellopontine angle (CPA) is rare. We describe a case of adult-type diffuse high-grade glioma of CPA in a 49-year-old female that was managed surgically at our institute. Glioblastoma is an infiltrating type of glioma (WHO grade 4). MRI helped in characterizing the lesion; however, diagnosis was confirmed on histopathology. This report aims at the imaging pattern of primary adult-type diffuse high-grade glioma (WHO grade 4) at cerebellopontine angle.

The review begins with an overview of the fundamental principles/physics underlying light, fluorescence, and other light-matter interactions in biological tissues. It then focuses on 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence spectroscopy methods used in neurosurgery (e.g., intensity, time-resolved) and in so doing, describe their specific features (e.g., hardware requirements, main processing methods) as well as their strengths and limitations. Finally, we review current clinical applications and future directions of 5-ALA-induced protoporphyrin IX (PpIX) fluorescence spectroscopy in neurosurgery.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare delayed complication of cranial radiotherapy, that may present decades after brain irradiation. Here we present a case of 41-year old patient with a history of grade 3 oligodendroglioma, epilepsy and migraine, 26 years after brain radiation therapy, who was admitted with right hemicranial headache, nausea, left homonymous hemianopsia, weakness of the left arm and left-sided hemihypesthesia. After considering alternate diagnoses, we ultimately diagnosed SMART syndrome. Despite its rare occurrence and unknown pathophysiology, there are more case reports of SMART syndrome reported due to advancements in oncology treatment and increasing patients’ survival rates. Therefore, diagnosis of SMART syndrome should always be considered in patients with a history of cranial radiation presenting with focal neurologic deficits and migraine, especially with a change in pattern of their usual migraine attack. [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]

Stroke-like migraine attacks after radiation therapy (SMART) syndrome is a rare delayed complication of cranial radiotherapy, that may present decades after brain irradiation. Here we present a case of 41-year old patient with a history of grade 3 oligodendroglioma, epilepsy and migraine, 26 years after brain radiation therapy, who was admitted with right hemicranial headache, nausea, left homonymous hemianopsia, weakness of the left arm and left-sided hemihypesthesia. After considering alternate diagnoses, we ultimately diagnosed SMART syndrome. Despite its rare occurrence and unknown pathophysiology, there are more case reports of SMART syndrome reported due to advancements in oncology treatment and increasing patients’ survival rates. Therefore, diagnosis of SMART syndrome should always be considered in patients with a history of cranial radiation presenting with focal neurologic deficits and migraine, especially with a change in pattern of their usual migraine attack.

Purpose of Review: The article gives an overview of the current knowledge in the management of tumor related epilepsy, including systematic reviews and consensus statements as well as recent insight into a potentially more individualized treatment approach. Recent Findings: Tumor molecular markers as IDH1 mutation and MGMT methylation status may provide future treatment targets. Seizure control should be included as a metric in assessing efficacy of tumor treatment. Summary: Prophylactic treatment is recommended in all brain tumor patients after the first seizure. Epilepsy has a profound effect on the quality of life in this patient group. The clinician should tailor the choice of seizure prophylactic treatment to the individual patient, with the goal of limiting adverse effects, avoiding interactions and obtaining a high degree of seizure freedom. Status epilepticus is associated with inferior survival and must be treated promptly. A multidisciplinary team should treat patients with brain tumors and epilepsy. [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]

This brief statement describes some recent achievements of neuropathological research, with the focus on Alzheimer’s and other age-related diseases, neurodegenerative disorders (tauopathies, synucleinopathies), multimorbidity of the aged brain, multiple sclerosis (MS), and other neuroinflammatory disorders, including central nervous system involvement by coronavirus disease 2019 (COVID-19), as well as new developments in neurovascular diseases, neurooncology, and myopathies. Although neuropathology, using modern technologies, such as cryo-electron microscopy, proteomic and experimental methods, has helped to increase diagnostic accuracy and provided insight into the pathogenesis of many neurological disorders, future studies in co-operation with clinical and other neurosciences should overcome the challenges of disease-influencing therapeutic approaches.

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]

Paediatric high-grade gliomas, including glioblastoma and anaplastic astrocytoma, make up 8%-12% of paediatric central nervous system tumours 1 and have poor prognosis, with 2-year survival less than 30% 2 and overall survival less than 10%. The only known prognostic factors in this population include extent of resection and tumour histological grade. We present the case of a 9-year-old boy with disseminated anaplastic astrocytoma treated with subtotal resection, craniospinal radiation and temozolomide, with 8-year survival despite metastatic disease at presentation and subtotal resection. Next generation cancer gene panel sequencing revealed an usual pattern of 12 amplifications and four mutations not previously described.

We present the case of a 13-year-old boy with a very unusual periventricular atypical central neurocytoma with unique molecular features treated with subtotal surgical resection and photon intensity-modulated radiotherapy. Histological features were most consistent with atypical central neurocytoma. However, next-generation sequencing analysis revealed a novel EWSR1-ATF1 gene fusion (EWSR1-ATF1) as well as a MUTYH mutation. The EWSR1-ATF1 raised the possibility of Ewing sarcoma or angiomatoid fibrous histiocytoma, however, FLI-1 immunohistochemistry was negative. MUTYH mutations have been reported in diffuse midline paediatric glioma. The role of EWSR1-ATF1 and MUTYH mutations in central nervous system tumours is not well established. We present the first case of EWSR1-ATF1 and MUTYH mutation in a rare paediatric atypical central neurocytoma. Further studies are indicated to elucidate the consequences of these gene alterations in the context of paediatric central nervous system tumours as well as to investigate the potential role for targeted therapies.

Abstract 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.

In our recent research, we have effectively demonstrated the feasibility of classifying magnetic resonance images (MRI) of glial tumors into four histological types utilizing standardized volume of interest (VOI), radiomics and machine learning. This research aims to determine the reproducibility of our approach when the locations of VOI are changed. We were able to demonstrate high reproducibility of ML results when the same feature selection methodology was employed across different VOIs. However, the reproducibility of radiomic features and their sets among various VOIs was not ensured for the sample size (n = 85) studied. The limited reproducibility of radiomic features should be taken into account when evaluating radiomics studies in glial tumors. [ABSTRACT FROM AUTHOR]

Metastatic spinal melanoma is a rare and aggressive disease process with poor prognosis. We review the literature on metastatic spinal melanoma, focusing on its epidemiology, management, and treatment outcomes. Demographics of metastatic spinal melanoma are similar to those for cutaneous melanoma, and cutaneous primary tumors tend to be most common. Decompressive surgical intervention and radiotherapy have traditionally been considered mainstays of treatment, and stereotactic radiosurgery has emerged as a promising approach in the operative management of metastatic spinal melanoma. While survival outcomes for metastatic spinal melanoma remain poor, they have improved in recent years with the advent of immune checkpoint inhibition, used in conjunction with surgery and radiotherapy. New treatment options remain under investigation, especially for patients with disease refractory to immunotherapy. We additionally explore several of these promising future directions. Nevertheless, further investigation of treatment outcomes, ideally incorporating high-quality prospective data from randomized controlled trials, is needed to identify optimal management of metastatic spinal melanoma.

Background: EWSR1::PATZ1 fusion tumors are exceedingly rare in the central nervous system with only 14 prior cases documented. PATZ1 fusion neuroepithelial tumors are beginning to be recognized as a distinct molecular class of neoplasms that most often occur in children and young adults. These tumors are polyphenotypic, show diverse morphologic features, may be low- or high-grade, and tend to have an intermediate prognosis. Case presentation: Herein, we present an unusual case of a high-grade neuroepithelial tumor in a young man with an EWSR1::PATZ1 fusion. This case is unique because the tumor appears to have undergone high-grade transformation from a persistent low-grade glioma, which has yet to be reported. Furthermore, this case is the first to document concurrent RB1 loss, SMAD4 loss, and TP53 inactivation in this tumor type, which correlates with high-grade transformation. Fortunately, this patient is alive 2.5 years after treatment and 18.5 years after initial presentation, which provides a unique window into how these tumors clinically behave over a long follow-up period. Finally, we discuss the altered molecular pathways that are a result of the EWSR1::PATZ1 fusion and discuss potential therapeutic targets. Conclusion: Awareness of the emerging entity of PATZ1 fusion neuroepithelial tumors is important not only for accurate diagnostic and prognostic purposes but also for predicting response to therapy. [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]

Opinion statement: Chimeric antigen receptor (CAR) T-cells are now a well-established treatment for hematologic malignancies. Their use in clinical practice has expanded quite rapidly and hospitals have developed CAR T-cell protocols to evaluate patients for associated toxicities, and particularly for neurotoxicity. There are many variables that influence the risk for developing this complication, many of which are not fully understood. The severity can be related to a particular product. Clinical vigilance is critical to facilitate early recognition of neurotoxicity, hence the importance of pre-CAR T-cell neurological evaluation of each patient. While details of such an evaluation may slightly differ between institutions, generally a comprehensive neurological evaluation including assessment of cognitive abilities along with magnetic resonance imaging (MRI) of the brain is a gold standard. Management of neurotoxicity requires a well-orchestrated team approach with specialists from oncology, neurology, oftentimes neurosurgery and neuro-intensive care. Diagnostic work-up frequently includes detailed neurologic evaluation with comparison to the baseline assessment, imaging of the brain, electroencephalogram, and lumbar puncture. While steroids are uniformly used for treatment, many patients also receive tocilizumab for an underlying and frequently concomitant cytokine release syndrome (CRS) in addition to symptom-driven supportive care. Novel CAR T-cell constructs and other agents allowing for potentially lower risk of toxicity are being explored. While neurotoxicity is predominantly an early, and reversible, event, a growing body of literature suggests that late neurotoxicity with variable clinical presentation can also occur. [ABSTRACT FROM AUTHOR]

Glioblastoma (GB) and brain metastasis (BM) are the most frequent types of brain tumors in adults. Their therapeutic management is quite different and a quick and reliable initial characterization has a significant impact on clinical outcomes. However, the differentiation of GB and BM remains a major challenge in today's clinical neurooncology due to their very similar appearance in conventional magnetic resonance imaging (MRI). Novel metabolic neuroimaging has proven useful for improving diagnostic performance but requires artificial intelligence for implementation in clinical routines. Here; we investigated whether the combination of radiomic features from MR-based oxygen metabolism ("oxygen metabolic radiomics") and deep convolutional neural networks (CNNs) can support reliably pre-therapeutic differentiation of GB and BM in a clinical setting. A self-developed one-dimensional CNN combined with radiomic features from the cerebral metabolic rate of oxygen (CMRO2) was clearly superior to human reading in all parameters for classification performance. The radiomic features for tissue oxygen saturation (mitoPO2; i.e., tissue hypoxia) also showed better diagnostic performance compared to the radiologists. Interestingly, both the mean and median values for quantitative CMRO2 and mitoPO2 values did not differ significantly between GB and BM. This demonstrates that the combination of radiomic features and DL algorithms is more efficient for class differentiation than the comparison of mean or median values. Oxygen metabolic radiomics and deep neural networks provide insights into brain tumor phenotype that may have important diagnostic implications and helpful in clinical routine diagnosis. [ABSTRACT FROM AUTHOR]

Glial‐lineage malignancies (gliomas) recurrently mutate and/or delete the master regulators of apoptosis p53 and/or p16/CDKN2A, undermining apoptosis‐intending (cytotoxic) treatments. By contrast to disrupted p53/p16, glioma cells are live‐wired with the master transcription factor circuits that specify and drive glial lineage fates: these transcription factors activate early‐glial and replication programs as expected, but fail in their other usual function of forcing onward glial lineage‐maturation—late‐glial genes have constitutively "closed" chromatin requiring chromatin‐remodeling for activation—glioma‐genesis disrupts several epigenetic components needed to perform this work, and simultaneously amplifies repressing epigenetic machinery instead. Pharmacologic inhibition of repressing epigenetic enzymes thus allows activation of late‐glial genes and terminates glioma self‐replication (self‐replication = replication without lineage‐maturation), independent of p53/p16/apoptosis. Lineage‐specifying master transcription factors therefore contrast with p53/p16 in being enriched in self‐replicating glioma cells, reveal a cause‐effect relationship between aberrant epigenetic repression of late‐lineage programs and malignant self‐replication, and point to specific epigenetic targets for noncytotoxic glioma‐therapy. [ABSTRACT FROM AUTHOR]

Recurrences of benign peripheral nerves sheaths tumours (BPNST) after total resection were described in 2.6–11.0% of patients. The significance of the histological features of recurrent BPNST is still insufficiently studied.Aim. To compare the pathomorphological features of recurrent and non-recurrent BPNST (schwannomas and neurofibromas).Materials and methods. A retrospective assessment was made of 101 patients with BPNST with a degree of anaplasia corresponding not more than Grade I. Recurrence of BPNST developed in 13 (12.9%) cases. The study included patients with histological archive: the study group (n = 7) included patients with one or more relapses of BPNST, the control group included patients (n = 5) without relapses after surgery for 5 or more years. The main clinical characteristics were studied and histological examination was performed.Results. There were no differences between the groups in baseline characteristics (the type of tumour (schwannoma, neurofibroma), distribution by sex, age, localization, clinical symptoms). The relapse rate among patients with neurofibromas was 8 in 3 patients vs. 6 in 5 patients with schwannomas. In all cases of recurrent schwannomas and in one of neurofibroma, the histological pattern was predominantly monophasic with rhythmic structures like Verocay bodies with underlined pattern and nuclear hyperchromasia, in contrast to the control group, represented by tumours with a mixed type of structure with uniform alternation of various histological patterns (p < 0,05). Endothelial proliferation and lymphocytic infiltration in the stroma and perivascular area were more common in the relapse group (p < 0.05). Pathomorphological signs of anaplasia: cell-nuclear polymorphism, nuclear hyperchromasia, endothelial proliferation, mitosis, as well as minor signs of anaplasia: solidization, muirization of the fascicular pattern of a tumour and apoptotic bodies were found with the same frequency in both groups. With relapse, the capsule was lost, thinned, intermittent, and sometimes invaded the surrounding tissues.Conclusion. Tumours with the initial signs of anaplasia, such as endothelial proliferation, tendency to hypercellularity, and histological pattern with prominent Verocay bodies dominate among recurrent BPNST.

BackgroundEWSR1::PATZ1 fusion tumors are exceedingly rare in the central nervous system with only 14 prior cases documented. PATZ1 fusion neuroepithelial tumors are beginning to be recognized as a distinct molecular class of neoplasms that most often occur in children and young adults. These tumors are polyphenotypic, show diverse morphologic features, may be low- or high-grade, and tend to have an intermediate prognosis.Case presentationHerein, we present an unusual case of a high-grade neuroepithelial tumor in a young man with an EWSR1::PATZ1 fusion. This case is unique because the tumor appears to have undergone high-grade transformation from a persistent low-grade glioma, which has yet to be reported. Furthermore, this case is the first to document concurrent RB1 loss, SMAD4 loss, and TP53 inactivation in this tumor type, which correlates with high-grade transformation. Fortunately, this patient is alive 2.5 years after treatment and 18.5 years after initial presentation, which provides a unique window into how these tumors clinically behave over a long follow-up period. Finally, we discuss the altered molecular pathways that are a result of the EWSR1::PATZ1 fusion and discuss potential therapeutic targets.ConclusionAwareness of the emerging entity of PATZ1 fusion neuroepithelial tumors is important not only for accurate diagnostic and prognostic purposes but also for predicting response to therapy.