Hybrid Positron Emission Tomography and Magnetic Resonance Imaging Guided Microsurgical Management of Glial Tumors: Case Series and Review of the Literature.

In this case series, we aimed to report our clinical experience with hybrid positron emission tomography (PET) and magnetic resonance imaging (MRI) navigation in the management of recurrent glial brain tumors. Consecutive recurrent neuroglial brain tumor patients who underwent PET/MRI at preoperative or intraoperative periods were included, whereas patients with non-glial intracranial tumors including metastasis, lymphoma and meningioma were excluded from the study. A total of eight patients (mean age 50.1 ± 11.0 years) with suspicion of recurrent glioma tumor were evaluated. Gross total tumor resection of the PET/MRI-positive area was achieved in seven patients, whereas one patient was diagnosed with radiation necrosis, and surgery was avoided. All patients survived at 1-year follow-up. Five (71.4%) of the recurrent patients remained free of recurrence for the entire follow-up period. Two patients with glioblastoma had tumor recurrence at the postoperative sixth and eighth months. According to our results, hybrid PET/MRI provides reliable and accurate information to distinguish recurrent glial tumor from radiation necrosis. With the help of this differential diagnosis, hybrid imaging may provide the gross total resection of recurrent tumors without harming eloquent brain areas.

Isocitrate Dehydrogenase Inhibitors in Glioma: From Bench to Bedside.

Isocitrate dehydrogenase (IDH) mutant gliomas are a primary malignancy of the central nervous system (CNS) malignancies, most commonly affecting adults under the age of 55. Standard of care therapy for IDH-mutant gliomas involves maximal safe resection, radiotherapy, and chemotherapy. However, despite good initial responses to multimodality treatment, recurrence is virtually universal. IDH-mutant gliomas represent a life-limiting prognosis. For this reason, there is a great need for novel treatments that can prolong survival. Uniquely for IDH-mutant gliomas, the IDH mutation is the direct driver of oncogenesis through its oncometabolite 2-hydroxygluterate. Inhibition of this mutated IDH with a corresponding reduction in 2-hydroxygluterate offers an attractive treatment target. Researchers have tested several IDH inhibitors in glioma through preclinical and early clinical trials. A phase III clinical trial of an IDH1 and IDH2 inhibitor vorasidenib yielded promising results among patients with low-grade IDH-mutant gliomas who had undergone initial surgery and no radiation or chemotherapy. However, many questions remain regarding optimal use of IDH inhibitors in clinical practice. In this review, we discuss the importance of IDH mutations in oncogenesis of adult-type diffuse gliomas and current evidence supporting the use of IDH inhibitors as therapeutic agents for glioma treatment. We also examine unresolved questions and propose potential directions for future research.

Navigating the Diagnosis and Treatment of Astroblastoma: A Pediatric Case Report.

Astroblastoma, a rare glial tumor of the central nervous system, presents diagnostic and therapeutic challenges due to its low incidence and variable clinical presentations. In this case study, we present the case of an 11-year-old boy with high-grade astroblastoma, highlighting the complexities in diagnosis and treatment. The clinical presentation initially involved right-sided motor weakness, which, after undergoing a brain MRI, revealed a large solid cystic mass in the left parietal lobe. Histopathological examination after undergoing surgery confirmed an astroblastoma with high-grade features, characterized by increased cellularity and high mitotic activity. Immunostaining patterns supported the glial origin of the tumor. Gross total resection remains the primary approach for its treatment, but adjuvant therapies for high-grade astroblastomas are still evolving, offering potential life-changing possibilities for the future. Due to its rarity, collecting sufficient data to develop an effective treatment protocol for this uncommon tumor is very challenging. This case underscores the importance of combined efforts and ongoing research to effectively navigate the diagnosis and treatment of astroblastoma.

MYCN immunohistochemistry as surrogate marker for MYCN-amplified spinal ependymomas.

MYCN (master regulator of cell cycle entry and proliferative metabolism) gene amplification defines a molecular subgroup of spinal cord ependymomas that show high-grade morphology and aggressive behavior. Demonstration of MYCN amplification by DNA methylation or fluorescence-in situ hybridization (FISH) is required for diagnosis. We aimed to (i) assess prevalence and clinicopathological features of MYCN-amplified spinal ependymomas and (ii) evaluate utility of immunohistochemistry (IHC) for MYCN protein as a surrogate for molecular testing. A combined retrospective-prospective study spanning 8 years was designed during which all spinal cord ependymomas with adequate tissue were subjected to MYCN FISH and MYCN IHC. Among 77 spinal cord ependymomas included, MYCN amplification was identified in 4 samples from 3 patients (3/74, 4%) including two (1st and 2nd recurrences) from the same patient. All patients were adults (median age at diagnosis of 32 years) including two females and one male. The index tumors were located in thoracic (n = 2) and lumbar (n = 1) spinal cord. One of the female patients had neurofibromatosis type 2 (NF2). All four tumors showed anaplastic histology. Diffuse expression of MYCN protein was seen in all four MYCN-amplified samples but in none of the non-amplified cases, thus showing 100% concordance with FISH results. On follow-up, the NF2 patient developed widespread spinal dissemination while another developed recurrence proximal to the site of previous excision. To conclude, MYCN-amplified spinal ependymomas are rare tumors, accounting for ~ 4% of spinal cord ependymomas. Within the limitation of small sample size, MYCN IHC showed excellent concordance with MYCN gene amplification.

Hemorrhagic presentation of previously silent brain tumors / Presentación hemorrágica de tumores cerebrales anteriormente silenciosos

Introduction and objectives Acute presentation with intracranial hemorrhage owing to a previously silent brain tumor (BT) is rare. Although any BT can bleed, the frequency and type of bleeding varies across tumor types. Materials and methods We aimed to retrospectively review our experience with 55 patients with BTs presenting with ICH. Results Signs of increased intracranial pressure were the most common symptoms. The temporal lobe was the most common lesion site (n=22). Hemorrhages were mainly confined to the tumor margins (HCTs) (n=34). Extensive intraparenchymal hemorrhages (EIHs) were mainly associated with moderately/severely decreased levels of consciousness (LOCs) (n=15/16). High-grade glioma (HGGT) (n=25) was the leading pathological diagnosis followed by metastasis (MBT) (n=16/55). The hemorrhage type was associated with the pathological diagnosis of the tumor. Patients with HGGT (n=19/25) and MBT (n=9/16) mainly presented with HCTs, whereas low-grade gliomas (LGGT) primarily caused EIHs (n=6/7). Conclusions Hemorrhagic presentation is a rare occurrence in BTs. Among all, MBT and HGGT are responsible for majority of the cases. Importantly, despite their relatively benign characteristics, LGGTs mainly result in extensive parenchymal destruction once they bleed. Maximum surgical resection of hemorrhagic BTs and decompression of the affected brain regions followed by histological confirmation of the diagnosis should be the main goals of treatment in cases with hemorrhagic BTs (AU)

Introducción y objetivos La presentación aguda con hemorragia intracraneal debida a un tumor cerebral (BT) anteriormente silencioso es rara. A pesar de que cualquier BT puede sangrar, la frecuencia y el tipo de sangrado varían según el tipo de tumor. Materiales y métodos Nuestro objetivo fue reexaminar retrospectivamente nuestra experiencia con 55 pacientes con los BT que presentaban HIC. Resultados Los síntomas más comunes fueron signos de aumento de la presión intracraneal. El lóbulo temporal fue el sitio de lesión más común (n=22). Las hemorragias se limitaron especialmente a los márgenes tumorales (HCT) (n=34). Las hemorragias intraparenquimatosas extensas (HIE) se asociaron mayormente con niveles de conciencia moderada/severamente disminuidos (LOC) (n=15/16). El glioma de alto grado (HGGT) (n=25) fue el principal diagnóstico patológico después de la metástasis (MBT) (n=16/55). El tipo de hemorragia se asoció con el diagnóstico patológico del tumor. Los pacientes con HGGT (n=19/25) y MBT (n=9/16) presentaron mayormente con HCT, mientras que los gliomas de bajo grado (LGGT) causaron principalmente HIE (n=6/7). Conclusiones La presentación hemorrágica es una ocurrencia rara en los BT. Entre todos, MBT y HGGT son responsables de la mayoría de los casos. Más importante aún, pese a sus características relativamente benignas, los LGGT resultan mayormente una destrucción extensa del parénquima una vez que sangran. La resección quirúrgica máxima de BT hemorrágicos y la descompresión de las regiones cerebrales afectadas con la confirmación histológica del diagnóstico deben ser los objetivos principales del tratamiento en casos con BT hemorrágicos (AU)

Surgical Treatment of a Supratentorial Extraventricular Ependymoma: A Case Report.

Supratentorial extraventricular ependymomas (STEE) are very rare primary tumors of the central nervous system (CNS). A 19-year-old man complained of headache, hemiparesis and seizures and was admitted to our hospital. Magnetic resonance imaging (MRI) revealed a right frontal intra-axial lesion. The patient underwent surgical treatment, and the tumor was resected successfully. A diagnosis of World Health Organization (WHO) grade 3 STEE was based on microscopic examination and immunohistochemical analysis. The patient was discharged without a neurological deficit.

The effects of radiotherapy on arterial diameters in patients with high-grade glial tumors who have undergone adjuvant radiotherapy.

Background and Aims: Our purpose was to evaluate the M2 branch of the middle cerebral artery (MCA) in high-grade glial tumor patients who undergo adjuvant radiotherapy (RT). For this purpose, the diameter of the M2 branch was measured and evaluated by means of contrast-enhanced magnetic resonance imaging (CE-MRI) before and after RT. Post-radiotherapeutical measurements were made 1, 3, 5, and 7 months after the procedure; and vascular diameter alterations were evaluated. Materials and Methods: CE-MRI examinations were performed on the 32 patients enrolled in the study, who had undergone radiotherapy of the temporoparietal region. MRI examinations were performed prior to RT (RT0) and 1 (RT1), 3 (RT2), 5 (RT3), and 7 (RT4) months after RT. The M2 branch of the MCA was evaluated on MRI images, and the vessel diameter was measured in millimeters (mm), and then comparisons were made. Results: Statistically significant results were obtained during RT0-RT1, RT0-RT2, RT0-RT3, RT0-RT4, RT1-RT2, RT2-RT4, and RT3-RT4, and comparisons of the diameters of the M2 branch of the right MCA were performed (P < 0.05). When the same measurements and comparisons were made for the M2 branch of the left MCA, statistically significant results were found for the RT1-RT2, RT1-RT3, and RT1-RT4 comparisons (P < 0.05). Conclusion: Our study showed that the MCA M2 branch diminished in size following RT. This was demonstrated by means of CE-MRI controls performed up to 7 months after the completion of the RT procedures.

The Current State of Adult Glial Tumor Patients' Care in Kazakhstan: Challenges in Diagnosis and Patterns in Survival Outcomes.

BACKGROUND: The study aimed to analyze the 5-year survival of adult patients with glial tumors and to define characteristics that are associated with the disease outcomes in Kazakhstan. METHODS: Medical records of patients that were surgically treated at the National Center for Neurosurgery during the 5-year period from 2016 to 2020 were collected retrospectively. Patients with a histologically confirmed diagnosis of diffuse astrocytic or oligodendroglial tumor type were included and their survival was assessed with life tables, Kaplan-Meier plot, and Cox regression using STATA 16 statistical software. RESULTS: Almost half of the patients had glioblastoma. The 5-year survival rate of the whole sample was 45.93%. Among Grade 4 patients, 15.6% survived the 5-year mark. Differences in survival between grades 1-3 were not significant. Grade 1 patients demonstrated worse survival rates compared to Grade 2 patients (69% vs. 74%). Worse survival rates were observed among patients of Russian ethnicity and in rural residents. CONCLUSIONS: The study described the unusual patterns in survival rates of glial tumor patients in Kazakhstan, pointing to the need for reassessment of diagnostic accuracy and resulting treatment of glial patients in Kazakhstan, and the need to introduce molecular and genetic parameters in tumor type classification. Moreover, the observed difference in survival of different ethnic groups and residents of rural and urban areas should be further investigated and addressed by healthcare professionals.

Hemorrhagic presentation of previously silent brain tumors.

INTRODUCTION AND OBJECTIVES: Acute presentation with intracranial hemorrhage owing to a previously silent brain tumor (BT) is rare. Although any BT can bleed, the frequency and type of bleeding varies across tumor types. MATERIALS AND METHODS: We aimed to retrospectively review our experience with 55 patients with BTs presenting with ICH. RESULTS: Signs of increased intracranial pressure were the most common symptoms. The temporal lobe was the most common lesion site (n=22). Hemorrhages were mainly confined to the tumor margins (HCTs) (n=34). Extensive intraparenchymal hemorrhages (EIHs) were mainly associated with moderately/severely decreased levels of consciousness (LOCs) (n=15/16). High-grade glioma (HGGT) (n=25) was the leading pathological diagnosis followed by metastasis (MBT) (n=16/55). The hemorrhage type was associated with the pathological diagnosis of the tumor. Patients with HGGT (n=19/25) and MBT (n=9/16) mainly presented with HCTs, whereas low-grade gliomas (LGGT) primarily caused EIHs (n=6/7). CONCLUSIONS: Hemorrhagic presentation is a rare occurrence in BTs. Among all, MBT and HGGT are responsible for majority of the cases. Importantly, despite their relatively benign characteristics, LGGTs mainly result in extensive parenchymal destruction once they bleed. Maximum surgical resection of hemorrhagic BTs and decompression of the affected brain regions followed by histological confirmation of the diagnosis should be the main goals of treatment in cases with hemorrhagic BTs.

Diffuse Leptomeningeal Glioneuronal Tumor: A Rare Case Report with Review of Literature.

Diffuse leptomeningeal glioneuronal tumor (DLGNT) is a rare tumor that was defined as a separate entity in the 2016 World Health Organization classification of brain tumors. It is most common in the pediatric age group. The diagnosis of this tumor can be made preoperatively by its characteristic imaging findings of diffuse intracranial and intraspinal nodular leptomeningeal thickening and enhancement associated with small cyst-like nonenhancing lesions in the brain and spinal cord. We report a case of DLGNT in a 7-year-old male presenting with hydrocephalus. The patient was treated successfully by cerebrospinal fluid (CSF) diversion followed by biopsy of the lesion from the cerebellum. Histopathology and immunohistochemistry confirmed the diagnosis of DLGNT. Our case would hopefully increase the awareness regarding this rare tumor and facilitate an early diagnosis and management of the affected patients with atypical radiological features.

Epilepsy treatment in neuro-oncology: A rationale for drug choice in common clinical scenarios.

Epilepsy represents a challenge in the management of patients with brain tumors. Epileptic seizures are one of the most frequent comorbidities in neuro-oncology and may be the debut symptom of a brain tumor or a complication during its evolution. Epileptogenic mechanisms of brain tumors are not yet fully elucidated, although new factors related to the underlying pathophysiological process with possible treatment implications have been described. In recent years, the development of new anti-seizure medications (ASM), with better pharmacokinetic profiles and fewer side effects, has become a paradigm shift in many clinical scenarios in neuro-oncology, being able, for instance, to adapt epilepsy treatment to specific features of each patient. This is crucial in several situations, such as patients with cognitive/psychiatric comorbidity, pregnancy, or advanced age, among others. In this narrative review, we provide a rationale for decision-making in ASM choice for neuro-oncologic patients, highlighting the strengths and weaknesses of each drug. In addition, according to current literature evidence, we try to answer some of the most frequent questions that arise in daily clinical practice in patients with epilepsy related to brain tumors, such as, which patients are the best candidates for ASM and when to start it, what is the best treatment option for each patient, and what are the major pitfalls to be aware of during follow-up.

Hybrid [18F]-F-DOPA PET/MRI Interpretation Criteria and Scores for Glioma Follow-up After Radiotherapy.

OBJECTIVE: 18F­fluoro-L­3,4­dihydroxyphenylalanine positron emission tomography (F­DOPA PET) is used in glioma follow-up after radiotherapy to discriminate treatment-related changes (TRC) from tumor progression (TP). We compared the performances of a combined PET and MRI analysis with F­DOPA current standard of interpretation. METHODS: We included 76 consecutive patients showing at least one gadolinium-enhanced lesion on the T1­w MRI sequence (T1G). Two nuclear medicine physicians blindly analyzed PET/MRI images. In addition to the conventional PET analysis, they looked for F­DOPA uptake(s) outside T1G-enhanced areas (T1G/PET), in the white matter (WM/PET), for T1G-enhanced lesion(s) without sufficiently concordant F­DOPA uptake (T1G+/PET), and F­DOPA uptake(s) away from hemorrhagic changes as shown with a susceptibility weighted imaging sequence (SWI/PET). We measured lesions' F­DOPA uptake ratio using healthy brain background (TBR) and striatum (T/S) as references, and lesions' perfusion with arterial spin labelling cerebral blood flow maps (rCBF). Scores were determined by logistic regression. RESULTS: 53 and 23 patients were diagnosed with TP and TRC, respectively. The accuracies were 74% for T/S, 76% for TBR, and 84% for rCBF, with best cut-off values of 1.3, 3.7 and 1.25, respectively. For hybrid variables, best accuracies were obtained with conventional analysis (82%), T1G+/PET (82%) and SWI/PET (81%). T1G+/PET, SWI/PET and rCBF ≥ 1.25 were selected to construct a 3-point score. It outperformed conventional analysis and rCBF with an AUC of 0.94 and an accuracy of 87%. CONCLUSIONS: Our scoring approach combining F­DOPA PET and MRI provided better accuracy than conventional PET analyses for distinguishing TP from TRC in our patients after radiation therapy.

Frequent FGFR1 hotspot alterations in driver-unknown low-grade glioma and mixed neuronal-glial tumors.

PURPOSE: Low-grade gliomas (LGG) and mixed neuronal-glial tumors (MNGT) show frequent MAPK pathway alterations. Oncogenic fibroblast growth factor receptor 1 (FGFR1) tyrosinase kinase domain has been reported in brain tumors of various histologies. We sought to determine the frequency of FGFR1 hotspot mutations N546 and K656 in driver-unknown LGG/MNGT and examined FGFR1 immunohistochemistry as a potential tool to detect those alterations. METHODS: We analyzed 476 LGG/MNGT tumors for KIAA-1549-BRAF fusion, IDH1/2, TERT promotor, NF1, H3F3A and the remaining cases for FGFR1 mutation frequency and correlated FGFR1 immunohistochemistry in 106 cases. RESULTS: 368 of 476 LGG/MNGT tumors contained non-FGFR1 alterations. We identified 9 FGFR1 p.N546K and 4 FGFR1 p.K656E mutations among the 108 remaining driver-unknown samples. Five tumors were classified as dysembryoplastic neuroepithelial tumor (DNT), 4 as pilocytic astrocytoma (PA) and 3 as rosette-forming glioneuronal tumor (RGNT). FGFR1 mutations were associated with oligodendroglia-like cells, but not with age or tumor location. FGFR1 immunohistochemical expression was observed in 92 cases. FGFR1 immunoreactivity score was higher in PA and DNT compared to diffuse astrocytoma, but no correlation between FGFR1 mutation in tumors and FGFR1 expression level was observed. CONCLUSION: FGFR1 hotspot mutations are the fifth most prevailing alteration in LGG/MNGT. Performing FGFR1 sequencing analysis in driver-unknown low-grade brain tumors could yield up to 12% FGFR1 N546/K656 mutant cases.

Berberine Photo-Activation Potentiates Cytotoxicity in Human Astrocytoma Cells through Apoptosis Induction.

Photodynamic therapy (PDT) has recently attracted interest as an innovative and adjuvant treatment for different cancers including malignant gliomas. Among these, Glioblastoma (GBM) is the most prevalent neoplasm in the central nervous system. Despite conventional therapeutic approaches that include surgical removal, radiation, and chemotherapy, GBM is characterized by an extremely poor prognosis and a high rate of recurrence. PDT is a physical process that induces tumor cell death through the genesis and accumulation of reactive oxygen species (ROS) produced by light energy interaction with a photosensitizing agent. In this contribution, we explored the potentiality of the plant alkaloid berberine (BBR) as a photosensitizing and cytotoxic agent coupled with a PDT scheme using a blue light source in human established astrocytoma cell lines. Our data mainly indicated for the combined BBR-PDT scheme a potent activation of the apoptosis pathway, through a massive ROS production, a great extent of mitochondria depolarization, and the sub-sequent activation of caspases. Altogether, these results demonstrated that BBR is an efficient photosensitizer agent and that its association with PDT may be a potential anticancer strategy for high malignant gliomas.

Analyses of DNA Methylation Profiling in the Diagnosis of Intramedullary Astrocytomas.

Intramedullary astrocytomas (IMAs) consist of a heterogeneous group of rare central nervous system (CNS) tumors associated with variable outcomes. A DNA methylation-based classification approach has recently emerged as a powerful tool to further classify CNS tumors. However, no DNA methylation-related studies specifically addressing to IMAs have been performed yet. In the present study, we analyzed 16 IMA samples subjected to morphological and molecular analyses, including DNA methylation profiling. Among the 16 samples, only 3 cases were classified in a reference methylation class (MC) with the recommended calibrated score (≥0.9). The remaining cases were either considered "no-match" cases (calibrated score <0.3, n = 7) or were classified with low calibrated scores (ranging from 0.32 to 0.53, n = 6), including inconsistent classification. To obtain a more comprehensive tool for pathologists, we used different unsupervised analyses of DNA methylation profiles, including our data and those from the Heidelberg reference cohort. Even though our cohort included only 16 cases, hypotheses regarding IMA-specific classification were underlined; a potential specific MC of PA_SPINE was identified and high-grade IMAs, probably consisting of H3K27M wild-type IMAs, were mainly associated with ANA_PA MC. These hypotheses strongly suggest that a specific classification for IMAs has to be investigated.

Papillary glioneuronal tumor growing slowly for 26 years: illustrative case.

BACKGROUND: Papillary glioneuronal tumors (PGNTs) are classified as a type of World Health Organization grade I mixed neuronal-glial tumor. Most PGNTs involve cystic formations with mural nodules and solid components in the cerebral hemispheres, and PGNTs occur mainly in young adults. The long-term prognosis of PGNTs remains unclear. OBSERVATIONS: A 38-year-old male had been diagnosed with an arachnoid cyst associated with epilepsy in a local hospital. The initial magnetic resonance imaging (MRI) study showed the tumor as a heterogeneously enhanced nodule in the left postcentral gyrus. Subsequent MRI studies showed slow growth of the tumor for 26 years. He underwent gross total resection to control his epilepsy. The histopathological findings revealed pseudopapillary structures involving hyalinized blood vessels with a single or pseudostratified layer of cuboidal glial cells with round nuclei and scant cytoplasm. At the periphery of the lesion, Rosenthal fibers and acidophilic granule bodies were observed in the gliotic brain tissue. Immunohistochemically, some interpapillary cells were positive for NeuN. On the basis of these findings, the tumor was diagnosed as a PGNT. LESSONS: This PGNT showed slow growth for 26 years. When recognizing a slowly growing tumor in the cerebral hemispheres of relatively young people that is associated with epileptic seizures, PGNT should be considered as a differential diagnosis.

68Ga PSMA PET/MR in the differentiation of low and high grade gliomas: Is 68Ga PSMA PET/MRI useful to detect brain gliomas?

BACKGROUND: Magnetic resonance imaging (MRI) is the most important imaging modality in the diagnosis and follow-up of glial brain tumors. OBJECTIVE: The aim of our study is to determine the correlation between tumor grade, determined with postoperative pathological examination, and standard uptake value (SUV), a semi-quantitative parameter, in patients who underwent imaging 68Ga-PSMA with using PET/MR. MATERIAL-METHOD: Thirty-five out of 38 patients' images whose pathology was consistent with glial tumor, 42 lesions from separate anatomic localizations or with higher activity uptake than the rest of the tumor were evaluated. SUV values measured on PET images and grade relationship were evaluated based on each lesion while mitosis, Ki-67 were evaluated for each patient. RESULTS: Grade, Ki-67, mitosis, necrosis and SUVmax/mean/peak were found statistically significant with moderate/high correlation. The parameter with the highest correlation coefficient was mitosis. (For SUVmax r = 0.64, p = 0). When Grade II and III were considered as the first group and IV as the second group, the cutoff values were found to be 2.3 for SUVmax, 0.21 for SUVmean and 0.63 for SUVpeak. In the diagnosis of HGG, PET's sensitivity is higher than MRI but no statistically difference was found between specificities. CONCLUSION: 68Ga PSMA PET imaging is found to be particularly useful in differentiating Grade IV glial tumors from other grades. This finding is thought to be important in the differentiation the relapse with postoperative tissue changes, which is an important problem in the follow-up.

Clinical, radiological and molecular characterization of intramedullary astrocytomas.

Intramedullary astrocytomas (IMAs) are rare tumors, and few studies specific to the molecular alterations of IMAs have been performed. Recently, KIAA1549-BRAF fusions and the H3F3A p.K27M mutation have been described in low-grade (LG) and high-grade (HG) IMAs, respectively. In the present study, we collected clinico-radiological data and performed targeted next-generation sequencing for 61 IMAs (26 grade I pilocytic, 17 grade II diffuse, 3 LG, 3 grade III and 12 grade IV) to identify KIAA1549-BRAF fusions and mutations in 33 genes commonly implicated in gliomas and the 1p/19q regions. One hundred seventeen brain astrocytomas were analyzed for comparison. While we did not observe a difference in clinico-radiological features between LG and HG IMAs, we observed significantly different overall survival (OS) and event-free survival (EFS). Multivariate analysis showed that the tumor grade was associated with better OS while EFS was strongly impacted by tumor grade and surgery, with higher rates of disease progression in cases in which only biopsy could be performed. For LG IMAs, EFS was only impacted by surgery and not by grade. The most common mutations found in IMAs involved TP53, H3F3A p.K27M and ATRX. As in the brain, grade I pilocytic IMAs frequently harbored KIAA1549-BRAF fusions but with different fusion types. Non-canonical IDH mutations were observed in only 2 grade II diffuse IMAs. No EGFR or TERT promoter alterations were found in IDH wild-type grade II diffuse IMAs. These latter tumors seem to have a good prognosis, and only 2 cases underwent anaplastic evolution. All of the HG IMAs presented at least one molecular alteration, with the most frequent one being the H3F3A p.K27M mutation. The H3F3A p.K27M mutation showed significant associations with OS and EFS after multivariate analysis. This study emphasizes that IMAs have distinct clinico-radiological, natural evolution and molecular landscapes from brain astrocytomas.

Symptomatic cerebral vasospasm in the setting of carmustine wafer placement for glioblastoma: A case presentation and review of literature.

BACKGROUND: Gliadel placement in glioblastoma resection, particularly with concurrent chemoradiation, has demonstrated an improvement in survival. There have been several reported adverse effects, some of which lend to significantly increased morbidity and mortality. With only two other cases described in literature, cerebral vasospasm secondary to carmustine-impregnated wafers is an extremely rare side effect. CASE DESCRIPTION: We report the case of a 51-year-old female who presented with the left lower limb paresis 8 days after high-grade glioma resection provoked by carmustine wafer placement. CONCLUSION: We urge surgeons to reconsider placement of carmustine wafers in nations where the surgical resection cavity includes exposed large cerebral vasculature. We also propose the early identification of this devastating complication in the postoperative period by maintaining a high clinical suspicion and prompt utilization of computed tomography and digital subtraction angiography in the management and treatment of these patients accordingly.

Caprylic (Octanoic) Acid as a Potential Fatty Acid Chemotherapeutic for Glioblastoma.

High grade glial tumors (HGGs) including anaplastic astrocytoma (WHO Grade-III) and glioblastoma multiforme (GBM, WHO Grade-IV) are among the most malignant cancers known to man. Due to their defective mitochondria, HGG cells consume glucose via glycolysis even in the presence of oxygen. Overall survival is worse in HGG patients that are hyperglycemic. Unlike normal neural cells, HGG cells cannot efficiently metabolize ketone bodies for energy. Thus, a metabolic treatment based on therapeutic ketosis (reduced glucose with elevated ketone bodies) was proposed to treat GBM and was supoported from preclinical studies. Caprylic (octanoic) acid, a monocarboxylated saturated fatty acid, is among the best producers of ketone bodies and induces necrosis of experimental tumors at high dose. Caprylic acid is enriched in coconut and in goat's milk. It is also a posttranslational modifier of the ghrelin hormone and is produced in trace amounts in human tissues. Caprylic acid is a straight-chain isomer of the antiepileptic valproic acid, which is used in treatment of HGG-associated seizures and which may increase survival in GBM patients according to epidemiological observations. Among the valproic acids analogs tested, caprylic acid is the most potent molecule to block C6 astrocytoma cell growth in vitro and accumulates selectively within glial cells as shown by Positron Emission Tomography in vivo. Caprylic acid blocks glycolysis both in healthy liver and in malignant liver cells, which is more prominent in the latter and also lowers blood glucose. Noteworthy, caprylic acid exerts neuroprotective- and mitochondria-protective effects in several models of neurodegenerative diseases. Boost injections of caprylic acid at non-toxic levels during classical ketogenic metabolic therapy may fortify antitumor actions and reduce systemic toxicity by differential programming of mitochondrial and other metabolic pathways.