Glioma is the most common primary brain tumor, characterized by a consistently high patient mortality rate and a dismal prognosis affecting both survival and quality of life. Substantial evidence underscores the vital role of the immune system in eradicating tumors effectively and preventing metastasis, underscoring the importance of cancer immunotherapy which could potentially address the challenges in glioma therapy. Although glioma immunotherapies have shown promise in preclinical and early-phase clinical trials, they face specific limitations and challenges that have hindered their success in further phase III trials. Resistance to therapy has been a major challenge across many experimental approaches, and as of now, no immunotherapies have been approved. In addition, there are several other limitations facing glioma immunotherapy in clinical trials, such as high intra- and inter-tumoral heterogeneity, an inherently immunosuppressive microenvironment, the unique tissue-specific interactions between the central nervous system and the peripheral immune system, the existence of the blood-brain barrier, which is a physical barrier to drug delivery, and the immunosuppressive effects of standard therapy. Therefore, in this review, we delve into several challenges that need to be addressed to achieve boosted immunotherapy against gliomas. First, we discuss the hurdles posed by the glioma microenvironment, particularly its primary cellular inhabitants, in particular tumor-associated microglia and macrophages (TAMs), and myeloid cells, which represent a significant barrier to effective immunotherapy. Here we emphasize the impact of inducing immunogenic cell death (ICD) on the migration of Th17 cells into the tumor microenvironment, converting it into an immunologically “hot” environment and enhancing the effectiveness of ongoing immunotherapy. Next, we address the challenge associated with the accurate identification and characterization of the primary immune profiles of gliomas, and their implications for patient prognosis, which can facilitate the selection of personalized treatment regimens and predict the patient’s response to immunotherapy. Finally, we explore a prospective approach to developing highly personalized vaccination strategies against gliomas, based on the search for patient-specific neoantigens. All the pertinent challenges discussed in this review will serve as a compass for future developments in immunotherapeutic strategies against gliomas, paving the way for upcoming preclinical and clinical research endeavors.

Glioma: bridging the tumor microenvironment, patient immune profiles and novel personalized immunotherapy

Review of the clinicopathologic and genetic features of early ependymal tumor with MN1-BEND2 fusion (EET MN1-BEND2), classical astroblastomas, and recently described related pediatric CNS tumors. I also briefly review general mechanisms of gene expression silencing by DNA methylation and chromatin remodeling, and genomic DNA methylation profiling as a powerful new tool for CNS tumor classification.Literature review and illustration of tumor histopathologic features and prenatal gene expression timelines.Astroblastoma, originally descried by Bailey and Cushing in 1926, has been an enigmatic tumor. Whether they are of ependymal or astrocytic derivation was argued for decades. Recent genetic evidence supports existence of both ependymal and astrocytic astroblastoma-like tumors. Studies have shown that tumors exhibiting astroblastoma-like histology can be classified into discrete entities based on their genomic DNA methylation profiles, gene expression, and in some cases, the presence of unique gene fusions. One such tumor, EET MN1-BEND2 occurs mostly in female children, and has an overall very good prognosis with surgical management. It contains a gene fusion comprised of portions of the MN1 gene at chromosomal location 22q12.1 and the BEND2 gene at Xp22.13. Other emerging pediatric CNS tumor entities demonstrating ependymal or astroblastoma-like histological features also harbor gene fusions involving chromosome X, 11q22 and 22q12 breakpoint regions.Genomic DNA profiling has facilitated discovery of several new CNS tumor entities, however, traditional methods, such as immunohistochemistry, DNA or RNA sequencing, and cytogenetic studies, including fluorescence in situ hybridization, remain necessary for their accurate biological classification and diagnosis. 

/pdf/early-ependymal-tumor-with-mn1-bend2-fusion-a-mostly-2pqrrjxt.pdf

Early ependymal tumor with MN1-BEND2 fusion: a mostly cerebral tumor of female children with a good prognosis that is distinct from classical astroblastoma

The uncommon MN1-altered primary central nervous system (CNS) tumors were recently added to the World Health Organization 2021 classification under the name Astroblastoma, MN1-altered. Another term used to describe them, “High-grade neuroepithelial tumor with MN1 alteration” (HGNET-MN1), makes reference to their distinct epigenetic profile but is currently not a recommended name. Thought to occur most commonly in children and predominantly in females, MN1-altered CNS tumors are associated with typical but not pathognomonic histological patterns and are characterized by a distinct DNA methylation profile and recurrent fusions implicating the MN1 (meningioma 1) gene. Diagnosis based on histological features alone is challenging: most cases with morphological features of astroblastoma (but not all) show these molecular features, whereas not all tumors with MN1 fusions show astroblastoma morphology. There is large variability in reported outcomes and detailed clinical and therapeutic information is frequently missing. Some patients experience multiple recurrences despite multimodality treatment, whereas others experience no recurrence after surgical resection alone, suggesting large clinical and biological heterogeneity despite unifying epigenetic features and recurrent fusions. In this report, we present the demographics, tumor characteristics, treatment, and outcome (including patient-reported outcomes) of three adults with MN1-altered primary CNS tumors diagnosed via genome-wide DNA methylation and RNA sequencing. All three patients were females and two of them were diagnosed as young adults. By reporting our neuropathological and clinical findings and comparing them with previously published cases we provide insight into the clinical heterogeneity of this tumor. Additionally, we propose a model for prospective, comprehensive, and systematic collection of clinical data in addition to neuropathological data, including standardized patient-reported outcomes.

/pdf/heterogeneous-clinicopathological-findings-and-patient-2awx3er6.pdf

Heterogeneous clinicopathological findings and patient-reported outcomes in adults with MN1-altered CNS tumors: A case report and systematic literature review

&lt;abstract&gt; &lt;p&gt;Trigeminal neuralgia is a debilitating condition characterized by severe facial pain. Carbamazepine has been widely used as a first-line treatment option for trigeminal neuralgia, but there is a need to evaluate its safety and efficacy based on existing evidence. This meta-analysis aims to systematically assess the available literature and provide a comprehensive evaluation of the safety and efficacy of carbamazepine in the treatment of trigeminal neuralgia. A thorough search of electronic databases yielded a total of 15 relevant studies that met the inclusion criteria. The pooled analysis of these studies revealed that carbamazepine demonstrated significant efficacy in reducing pain intensity and frequency in patients with trigeminal neuralgia. Moreover, the drug was generally well-tolerated, with the most common adverse events being mild and transient. Subgroup analyses based on different dosages and treatment durations further supported the overall findings. However, caution should be exercised in patients with certain comorbidities or specific populations, as some rare but severe adverse events were reported. In conclusion, this meta-analysis provides strong evidence supporting the safety and efficacy of carbamazepine as a valuable therapeutic option for the management of trigeminal neuralgia. These results can guide clinicians in making informed decisions regarding the use of carbamazepine and contribute to optimizing treatment strategies for patients with trigeminal neuralgia. Further research is warranted to explore long-term safety and efficacy outcomes, as well as to compare carbamazepine with alternative treatment modalities.&lt;/p&gt; &lt;/abstract&gt; 

Safety and efficacy of carbamazepine in the treatment of trigeminal neuralgia: A metanalysis in biomedicine

Introduction: Microvascular decompression (MVD) is an efficacious neurosurgical intervention for patients with medically intractable neurovascular compression syndromes. However, MVD may occasionally cause life-threatening or altering complications, particularly in patients unfit for surgical operations. Recent literature suggests a lack of association between chronological age and surgical outcomes for MVD. The Risk Analysis Index (RAI) is a validated frailty tool for surgical populations (both clinical and large database). The present study sought to evaluate the prognostic ability of frailty, as measured by RAI, to predict outcomes for patients undergoing MVD from a large multicenter surgical registry. Methods: The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database (2011–2020) was queried using diagnosis/procedure codes for patients undergoing MVD procedures for trigeminal neuralgia (n = 1,211), hemifacial spasm (n = 236), or glossopharyngeal neuralgia (n = 26). The relationship between preoperative frailty (measured by RAI and 5-factor modified frailty index [mFI-5]) for primary endpoint of adverse discharge outcome (AD) was analyzed. AD was defined as discharge to a facility which was not home, hospice, or death within 30 days. Discriminatory accuracy for prediction of AD was assessed by computation of C-statistics (with 95% confidence interval) from receiver operating characteristic (ROC) curve analysis. Results: Patients undergoing MVD (N = 1,473) were stratified by RAI frailty bins: 71% with RAI 0–20, 28% with RAI 21–30, and 1.2% with RAI 31+. Compared to RAI score 19 and below, RAI 20 and above had significantly higher rates of postoperative major complications (2.8% vs. 1.1%, p = 0.01), Clavien-Dindo grade IV complications (2.8% vs. 0.7%, p = 0.001), and AD (6.1% vs. 1.0%, p < 0.001). The rate of primary endpoint was 2.4% (N = 36) and was positively associated with increasing frailty tier: 1.5% in 0–20, 5.8% in 21–30, and 11.8% in 31+. RAI score demonstrated excellent discriminatory accuracy for primary endpoint in ROC analysis (C-statistic: 0.77, 95% CI: 0.74–0.79) and demonstrated superior discrimination compared to mFI-5 (C-statistic: 0.64, 95% CI: 0.61–0.66) (DeLong pairwise test, p = 0.003). Conclusions: This was the first study to link preoperative frailty to worse surgical outcomes after MVD surgery. RAI frailty score predicts AD after MVD with excellent discrimination and holds promise for preoperative counseling and risk stratification of surgical candidates. A risk assessment tool was developed and deployed with a user-friendly calculator: https://nsgyfrailtyoutcomeslab.shinyapps.io/microvascularDecompression.

Preoperative Frailty Predicts Worse Outcomes after Microvascular Decompression for Trigeminal Neuralgia, Hemifacial Spasm, and Glossopharyngeal Neuralgia: A Multicenter Analysis of 1,473 Patients from a Prospective Surgical Registry

Trigeminal Neuralgia: Diagnosis and Treatment.

Background: Astroblastoma is a rare primary brain tumor of unclear origin, often occurring in young patients less than 30-years-old. It typically arises supratentorially and is diagnosed based on histological features including vascular hyalinization and perivascular pseudorosettes. Recent molecular characterization of primary CNS high-grade neuroepithelial tumors with meningioma I alteration (HGNET-MN1) found that HGNET-MN1 and tumors with morphological signatures of astroblastoma clustered together. Further analysis revealed such astroblastomas have MN1 alteration and the 2021 WHO classification of tumors of the CNS now recognizes astroblastoma MN1-altered as a new entity. Case Description: Here, we present the case of a 36-year-old right-handed woman with recurrent low-grade astroblastoma in the cervicomedullary junction. The patient presented with worsening motor and sensory deficits of her upper extremities, pain, ataxia, visual disturbance, and nausea. Due to extensive recurrence and neurological symptoms, the patient underwent reoperation. Conclusion: We review a rare case of recurrent astroblastoma in the foramen magnum in light of new relevant literature about tumor biology and prognostic significance of the new classification of astroblastoma MN1-altered.

https://surgicalneurologyint.com/wp-content/uploads/2022/04/11544/SNI-13-139.pdf

Recurrent HGNET-MN1 altered (astroblastoma MN1-altered) of the foramen magnum: Case report and molecular classification

BACKGROUND: Vagus nerve stimulation (VNS) is a neuromodulatory procedure most extensively studied as an adjunct to medically refractory epilepsy. Despite widespread adoption and decades of clinical experience, clinical predictors of response to VNS remain unclear. OBJECTIVE: To evaluate a retrospective cohort of pediatric patients undergoing VNS at our institution to better understand who may benefit from VNS and identify factors which may predict response to VNS. METHODS: We conducted a retrospective cohort study examining pediatric patients undergoing VNS over nearly a 20-year span at a single institution. Presurgical evaluation, including demographics, clinical history, and diagnostic electroencephalogram, and imaging findings were examined. Primary outcomes included VNS response. RESULTS: Two hundred ninety-seven subjects were studied. The mean age at surgery was 10.1 (SD = 4.9, range = 0.8-25.3) years; length of follow-up was a mean of 4.6 years (SD = 3.5, median = 3.9 years, range 1 day-16.1 years). There was no association between demographic factors, epilepsy etiology, or genetic basis and VNS outcomes. There was an association between reduction in main seizure type with positive MRI finding. Of all MRI findings analyzed, brain atrophy was significantly associated with worse VNS outcomes, whereas dysplastic hippocampus and chronic periventricular leukomalacia findings were found to be associated with improved outcomes. Increased seizure semiology variability and seizure type were also associated with improved seizure outcomes. CONCLUSION: Predicting response to VNS remains difficult, leading to incompletely realized benefits and suboptimal resource utilization. Specific MRI findings and increased seizure semiology variability and type can help guide clinical decision making and patient counseling.

Pediatric Vagus Nerve Stimulation: Case Series Outcomes and Future Directions

A retrospective study was conducted in a tertiary care hospital in which the cytological diagnosis of palpable lesion of breast was compared with histopathological diagnosis to see the accuracy of cytology for both benign and neoplastic lumps in breast. A total number of 101 fine needle aspiration cytology was performed over a period of two years in cases of breast lump. The cytological and histological correlation was found in 51 cases (50%) out of 101cases. The commonest benign lesion was fibroadenoma, which was noted in age group of 15-35 years and the commonst malignant lesion was infiltrating ductal carcinoma, which was noted in the age group of 50-70 years. Thus the present study revealed that FNAC had Sensitivity of 50%, Specificity of 100%, Positive predictive value 100%, Negative predictive value 95.9% and the overall accuracy of the study was 96.1%.

To compare the diagnostic accuracy of FNAC with histopathology in benign and malignant breast lumps

Background: Liponeurocytomas are rare neurocytic neoplasms that most often arise in the posterior fossa and affect individuals in the third and fifth decades of life. Most reported cases of this unique tumor in the literature have described a favorable clinical prognosis without recurrence. However, increasing reports of recurrent cases prompted the World Health Organization, in 2016, to recategorize the tumor from Grade I to the less favorable Grade II classification. We conducted a systematic review to identify recurrent cases of this unique tumor and to summarize differences between the primary and recurrent cases of liponeurocytoma. Methods: A systematic review exploring recurrent liponeurocytoma cases was conducted by searching the PubMed, Google Scholar, and Scopus databases for articles in English. Abstracts from articles were read and selected for full-text review according to a priori criteria. Relevant full-text articles were analyzed for symptoms, imaging, location, histological, pathological, treatment, and recurrence-free time between the primary and recurrent cases. Results: Of 4392 articles, 15 articles accounting for 18 patients were included (level of evidence: IV) in the study. Recurrence-free time decreased from an average of 82 months between the primary tumor resection to first recurrence to 31.3 months between the first and second recurrence. Recurrent tumors demonstrated increased pleomorphic neural cells, necrosis, vascular proliferation, and MIB-1 index when compared to the primary tumor. Several cases also demonstrated decreased lipidizing components when compared to the primary tumor, further indicating increased dedifferentiation. The primary treatment for this tumor was surgical resection with occasional adjunctive radiotherapy. Conclusion: Recurrent cases of liponeurocytoma have features of increased malignant proliferation compared to the primary cases. The standard treatment for these primary and recurrent tumors is gross total resection. The role of adjunctive radiotherapy remains a matter of debate.

Recurrent liponeurocytoma: A case report and systematic review of the literature

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