Characterizing the Linkage of Systemic Hypoxia and Angiogenesis in High-Grade Glioma to Define the Changes in Tumor Microenvironment for Predicting Prognosis.

High-grade gliomas (HGG) comprising WHO grades 3 and 4 have a poor overall survival (OS) that has not improved in the past decade. Herein, markers representing four components of the tumor microenvironment (TME) were identified to define their linked expression in TME and predict the prognosis in HGG, namely, interleukin6 (IL6, inflammation), inducible nitric oxide synthase(iNOS), heat shock protein-70 (HSP70, hypoxia), vascular endothelial growth receptor (VEGF), and endothelin1 (ET1) (angiogenesis) and matrix metalloprotease-14 (MMP14) and intercellular adhesion molecule1 (ICAM1, extracellular matrix). To establish a non-invasive panel of biomarkers for precise prognostication in HGG. Eighty-six therapy-naive HGG patients with 45 controls were analyzed for the defined panel. Systemic expression of extracellular/secretory biomarkers was screened dot-immune assay (DIA), quantified by ELISA, and validated by immunocytochemistry (ICC). Expression of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 was found to be positively associated with grade. Quantification of circulating levels of the markers by ELISA and ICC presented a similar result. The biomarkers were observed to negatively correlate with OS (p < 0.0001). Cox-regression analysis yielded all biomarkers as good prognostic indicators and independent of confounders. On applying combination statistics, the biomarker panel achieved higher sensitivity than single markers to define survival. The intra-association of all seven biomarkers was significant, hinting of a cross-talk between the TME components and a hypoxia driven systemic inflammation upregulating the expression of other components. This is a first ever experimental study of a marker panel that can distinguish between histopathological grades and also delineate differential survival using liquid biopsy, suggesting that markers of hypoxia can be a cornerstone for personalized therapy. The panel of biomarkers of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 holds promise for prognostication in HGG.

Glioblastoma Multiforme miRNA based Comprehensive Study to Validate Phytochemicals for Effective Treatment against Deadly Tumour through In Silico Evaluation.

BACKGROUND: Glioblastoma Multiforme (GBM) is a prevalent and deadly type of primary astrocytoma, constituting over 60% of adult brain tumors, and has a poor prognosis, with a high relapse rate within 7 months of diagnosis. Despite surgical, radiotherapy, and chemotherapy treatments, GBM remains challenging due to resistance. MicroRNA (miRNAs) control gene expression at transcriptional and post-transcriptional levels by targeting their messenger RNA (mRNA), and also contribute to the development of various neoplasms, including GBM. METHODS: The present study focuses on exploring the miRNAs-based pathogenesis of GBM and evaluating most potential plant-based therapeutic agents with in silico analysis. Gene chips were retrieved from the Gene Expression Omnibus (GEO) database, followed by the Robust- RankAggereg algorithm to determine the Differentially Expressed miRNAs (DEMs). The predicted targets were intersected with the GBM-associated genes, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the overlapping genes was performed. At the same time, five phytochemicals were selected for the Connectivity map (CMap), and the most efficient ones were those that had undergone molecular docking analysis to obtain the potential therapeutic agents. RESULTS: The hsa-miR-10b, hsa-miR-21, and hsa-miR-15b were obtained, and eight genes were found to be associated with glioma pathways; VSIG4, PROCR, PLAT, and ITGB2 were upregulated while, CAMK2B, PDE1A, GABRA1, and KCNJ6 were downregulated. The drugs Resveratrol and Quercetin were identified as the most prominent drugs. CONCLUSION: These miRNAs-based drugs can be used as a curative agent for the treatment of GBM. However, in vivo, experimental data, and clinical trials are necessary to provide an alternative to conventional GBM cancer chemotherapy.

Revisiting Post-Laminectomy Kyphosis and Challenges in Its Management: A Case Report.

The posterior ligamentous complex plays a pivotal role in spinal stability during complex movements, especially at the cervical vertebral level. Its disruption leads to the development of post-laminectomy kyphosis. The present case emphasizes the challenges in managing post-laminectomy kyphosis, restoring spinal alignment, and the importance of the posterior tension band as a spine stabilizer. A 19-year-old male underwent C2-C5 laminectomy for cervical C3 neurofibroma at an outside hospital. The patient remained stable for five months and then developed cervical kyphosis, leading to myelopathy. Clinical examination revealed significant neurological deficits, including spasticity, clonus, loss of hand dexterity, and sensory abnormalities. Imaging revealed C3 retrolisthesis with severe cervical kyphosis, cord compression, and myelomalacia. The management involved cervical traction with gradual increments in the weight and correction of the cervical sagittal balance. Principles of kyphotic deformity correction were applied, and C2 pedicle with C3-C5 lateral mass fixation was performed. The patient's modified Japanese Orthopaedic Association score improved from 10 to 16 at six months' follow-up. Post-laminectomy, the disruption of the posterior ligamentous complex increases the range of motion, particularly in the cervical spine, leading to instability and kyphosis. Surgical interventions such as laminoplasty, laminotomy, and laminectomy with posterior cervical fusion aim to mitigate the risk of kyphosis, with techniques such as bone-to-bone ligament-preserving laminoplasty and ultrasonic bone scalpel showing promise in further reducing the risk of kyphosis. The key determinant for the prevention of kyphosis is the integrity of the posterior ligamentous complex. The management of cervical kyphosis includes appropriate pre-operative planning, which includes the evaluation of cervical and spinopelvic parameters. For a posterior spinal approach, one may choose to consider laminotomy, laminoplasty, or laminectomy along with posterior cervical fusion.

The spectrum of microvascular patterns in adult diffuse glioma and their correlation with tumor grade.

BACKGROUND: Primary brain tumors constitute the leading cause of cancer-related mortality. Among them, adult diffuse gliomas are the most common type, affecting the cerebral hemispheres and displaying a diffuse infiltrative pattern of growth in the surrounding neuropil that accounts for about 80% of all primary intracranial tumors. The hallmark feature of gliomas is blood vessel proliferation, which plays an important role in tumor growth, tumor biological behavior, and disease outcome. High-grade gliomas exhibit increased vascularity, the worst prognosis, and lower survival rates. Several angiogenic receptors and factors are upregulated in glioblastomas and stimulate angiogenesis signaling pathways by means of activating oncogenes and/or down-regulating tumor-suppressor genes. Existing literature has emphasized that different microvascular patterns (MVPs) are displayed in different subtypes of adult diffuse gliomas. METHODS: We examined the distribution and biological characteristics of different MVPs in 50 patients with adult diffuse gliomas. Haematoxylin and eosin staining results, along with periodic acid-Schiff and CD34 dual-stained sections, were examined to assess the vascular patterns and correlate with different grades of diffuse glioma. RESULTS: The present observational study on adult diffuse glioma evaluated tumor grade and MVPs. Microvascular sprouting was the most common pattern, while a bizarre pattern (type 2) was associated with the presence of a high-grade glioma. Vascular mimicry was observed in 6% of cases, all of which were grade 4 gliomas. CONCLUSIONS: This study supplements the role of neo-angiogenesis and aberrant vasculature patterns in the grading and progression of adult diffuse gliomas, which can be future targets for planning treatment strategies.

Endoscopy-Assisted Microneurosurgery for Sella and Optic Foramen Invading Anterior Cranial Fossa Base Meningiomas.

BACKGROUND: Anterior skull base meningioma produces symptoms as a result of mass effect and neurovascular compression. The bony anatomy of the anterior skull base is complex and houses the critical cranial nerves and vessels. Traditional microscopic approaches remove these tumors effectively but require extensive brain retraction and bone drilling. Endoscope assistance offers the advantages of a smaller incision, less brain retraction, and bone drilling. The most significant advantage of endoscope-assisted microneurosurgery for lesions invading the sella and optic foramen is the complete resection of the sellar and foraminal components frequently responsible for recurrence. OBJECTIVE: In this report, we describe the technique of endoscope-assisted microneurosurgical resection of anterior skull base meningiomas invading the sella and foramen. METHODS: We present 10 cases and 3 case examples of endoscope-assisted microneurosurgery for meningiomas invading the sella and optic foramen. This report presents the operating room setup and surgical details to resect sellar and foraminal tumors. The surgical procedure is presented as a video. RESULTS: Endoscope-assisted microneurosurgery yielded excellent clinical and radiologic results and no recurrence at the last follow-up of meningiomas invading the sella and optic foramen. The present article discusses the challenges faced with endoscope-assisted microneurosurgery, techniques, and challenges in the procedure. CONCLUSIONS: Endoscope assistance enables complete tumor excision under vision with less retraction and bone drilling in anterior cranial fossa meningioma, invading the chiasmatic sulcus, optic foramen, and sella. The mixed use of microscope and endoscope makes it safer and saves time and is like bringing out the best of both worlds.

Non-dysraphic extramedullary intradural spinal lipoma with neurocutaneous melanocytosis.

INTRODUCTION: Intradural spinal lipomas are very rare and constitute less than 1% of all spinal tumors. Such tumors are usually associated with spinal dysraphism and occur mostly in the lumbosacral or cervical region. Intradural spinal lipomas tends to be intramedullary or subpial. Meningeal melanocytoma is further rarer cases that comprise less than 0.1% of cases. These usually occur in the fifth or fifth decade and chances of malignant transformation are high. CASE REPORT: Here, we report an extremely rare case (first to the best of our knowledge) of a 9 years female child who presented to us with rapid progressing paraparesis. She was operated and found to have an intradural purely extramedullary spinal lipoma without spinal dysraphism. Moreover, she had melanin pigment deposits all over her meninges which is further rare. On presentation, the patient was bedridden but after surgery, the patient improved and could walk without support. CONCLUSIONS: To the best of our knowledge, this is the first case of spinal cord lipoma in dorsal location along with melanin pigments in the meninges. We discuss the pathogenesis, presentation and management of intradural extramedullary spinal lipomas.

Systematic scoping review of papilledema in vestibular schwannoma without hydrocephalus.

BACKGROUND: Vestibular schwannoma is a common pathology encountered by neurosurgeons worldwide. Often vestibular schwannoma presents with obstructive hydrocephalus. Papilledema is present in 8% of the patients with vestibular schwannoma, primarily due to obstructive hydrocephalus. Hyperproteinorrhachia is believed to be responsible for papilledema in the absence of hydrocephalus in vestibular schwannoma. However, there is a paucity of literature on the mechanism of papilledema in vestibular schwannoma patients with hydrocephalus. OBJECTIVE: The aim of this study was to conduct a scoping review of scientific literature on papilledema in vestibular schwannoma patients without hydrocephalus. METHODS: Design: This was a systematic scoping review and critical appraisal. Literature Search from PubMed was done following PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) and Joanna Briggs Institute guidelines for conducting and reporting scoping reviews. RESULTS: A total of seven studies, including eight patients, were identified for inclusion in the review. The studies were heterogeneous in terms of reporting for various variables. All the included studies were case reports, with the earliest publication in 1954 and the latest publication in 2020. The mean age of the patients in the included studies was 35 years, with a minimum age of 20 years and maximum age of 64 years. Approximately 62.5% were females, and 37.5% were males in the included study. Only three studies have studied cerebrospinal fluid (CSF) proteins levels in these patients. CONCLUSIONS: There is paucity in literature and a lack of evidence to conclusively state hyperproteinorrhachia as an antecedent to the development of papilledema in vestibular schwannoma patients without hydrocephalus. Younger age and female gender are risk factors for developing papilledema in the absence of hydrocephalus in vestibular schwannoma patients. Brainstem compression due to the large size of vestibular schwannoma can still have a patent aqueduct of Sylvius and no obstruction to CSF flow. The development of papilledema in vestibular schwannoma is a complex interplay of multiple factors that must be studied comprehensively for complete understanding.

Clinical and Radiological Characteristics for Recurrence of Chronic Subdural Hematoma: A Systematic Review and Meta-Analysis.

Chronic subdural hematoma (cSDH) is one of the most studied clinical entities in the neurosurgical literature. Management of cSDH is complicated by its propensity to recurrence. Various factors for the development of recurrence of cSDH have been described in various clinical, epidemiological, and observational studies, yet the evidence available is limited. A systematic review and meta-analysis as per PRISMA guidelines to identify clinical and radiological factors which can predict the development of recurrence in cSDH. A total of 14 studies were included for the systematic review and meta-analysis after a comprehensive search of the online databases. Eight studies were of high methodological quality. Age, use of anticoagulants, obesity, seizure, and liver disease were found to be statistically significant clinical risk factors for the development of recurrence in cSDH. Among the radiological parameters, the internal structure of the hematoma and the width of the hematoma was found to be significant risk factor predicting the development of recurrence. Age >75 years, use of anticoagulation therapy, liver disease, and obesity were significant risk factors for cSDH recurrence. Pneumocephalus, internal architecture of hematoma, bilateral cSDH, the width of hematoma, and the presence of bilateral cSDH are important radiological parameters of the development of recurrent cSDH

Obesity as a predictor of outcome following traumatic brain injury: A systematic review and meta-analysis.

INTRODUCTION: Obesity adversely affects the outcome in trauma patients. However, the impact of obesity on the severity of traumatic brain injury (TBI) and outcomes is not well known. This study aimed to explore the impact of obesity/body mass index on the severity and outcomes following TBI. METHODS: A systematic review of the literature was conducted using PRISMA guidelines to answer three questions: Q1: Is obesity/increased BMI associated with less risk of head injury? Q2: Whether obesity is associated with less severity of head injury? Q3: What is the impact of obesity/BMI on outcomes following head injury? A comprehensive search using keywords and MeSH terms was conducted in PUBMED, Cochrane database, Google Scholar, SCOPUS, WEB of Science Core Collection, and ScIELO index (Last day of search 06.06.2021). We used the Newcastle-Ottawa assessment scale (NOS) to evaluate the quality of studies and the Cochrane ROBANS tool to evaluate the risk of bias. Data extraction was done using piloted forms, and meta-analysis was done using the Mantel-Haenszel method. RESULTS: A total of 1088 citations were obtained with the search strategy. Eighteen studies matched inclusion and exclusion criteria and were included in the systematic review. The median quality of studies was 7/9 in NOS. There were fewer occurrences of head injury in obese individuals with an odd's ratio of 0.80% and 95% CI (0.69-0.93) with p = 0.004. More patients with BMI ≥ 30 had GCS ≤ 8 than patients with BMI < 30 with OR 1.08 (95%CI: 1.02-1.14). Obese patients had a more severe head injury (as per AIS) (58.9% vs 44.2%) and OR 1.83 (95%CI: 1.72-1.94), I2 = 87% and p < 0.00001. Length of ICU stay was more in obese individuals with a standard mean difference of 0.29 (95% CI: 0.03-0.55), I2 = 87%, p = 0.03. Similarly, obese individuals had a more extended hospital stay. There was no difference in mortality or ventilator days between obese and non-obese TBI patients. CONCLUSIONS: Obesity was associated with lower incidence and higher severity of head injury. However, there was no conclusive evidence that obesity confers protection from sustaining a head injury. Though the length of hospital and ICU stay were longer in obese individuals, the impact of obesity on mortality was not significant. There was no conclusive evidence for association of obesity with long term functional outcome or mortality following TBI.

Analysis of dynamic changes in optic nerve sheath diameter (ONSD) with ultrasound in post-craniotomy patients: Trends and correlation with computed tomography ONSD and Glasgow coma scale in post-operative period.

Objectives: Intracranial pressure (ICP) monitoring in patients with intracranial tumors undergoing craniotomy is usually done in perioperative period in intensive care unit. Invasive measurement of ICP, though considered as the gold standard, has its own limitations such as availability of expertise, equipment, and associated complications. Period of raised ICP in post-operative period may impact patient outcomes. Post-craniotomy computed tomography (CT) assessment is done routinely and may need to be repeated if indicated during post-operative stay. Utility of sonographic serial optic nerve sheath diameter (ONSD) assessment in post-operative monitoring of patients who have undergone elective craniotomy was explored in this study. The primary objective of the study was to measure the dynamic change in ONSD as compared to baseline pre-operative measurement in the first 3 postoperative days after elective craniotomy. The secondary objective of the study was to evaluate correlation between ONSD value with Glasgow Coma Scale (GCS) and post-operative CT findings. Materials and Methods: In this prospective, observational, and cohort study, we studied adult patients undergoing craniotomy for intracranial tumors. GCS assessment and sonographic measurement of ONSD were done preoperatively, immediate post-operative period, and 12, 24, and 48 h after surgery. CT scan to detect raised ICP was done at 24 h post-operative. Correlation of ONSD with GCS at respective period and correlation of CT scan finding with respective ONSD assessment were evaluated. Results: A total of 57 patients underwent elective craniotomy for intracranial tumors. Significant difference was observed in ONSD value depending on time of measurement perioperatively (χ2 = 78.9, P = 0.00). There was initial increase in the first 12 h followed by decrease in ONSD in the next 48 h. Negative correlation was observed between baseline ONSD and 12 h GCS (ρ = -0.345, P = 0.013). There was significant change in GCS scores based on the status of ONSD (raised or normal) at 12 h after surgery (P = 0.014). Significant correlation between USG ONSD and CT ONSD was observed (ρ = 0.928, P = 0.000). Optimal cutoff value of ONSD to detect raised ICP with reference to CT signs was 4.8 mm with 80% sensitivity and 95% specificity. Conclusion: ONSD undergoes dynamic changes, correlates with CT scan, and has good diagnostic accuracy to detect raised ICP post-craniotomy for intracranial tumors. It may serve as a useful tool in monitoring in resource-limited setup.

A Rare, yet Classic Case of Colloid Cyst of Third Ventricle.

Colloid cyst of third ventricle is a rare, benign, congenital lesion that usually presents with headache, and associated with altered cognition, nausea, vomiting, gait ataxia, and blurred vision. A large cyst/growing cyst can cause obstructive hydrocephalus leading to acute rapid neurological deterioration and sudden death. Here we report a classic clinical presentation and histopathological features of colloid cyst of third ventricle with specific emphasis on the importance of rapid diagnosis and management to avoid potentially fatal complications of this otherwise benign lesion. Newer modalities like neuroendoscopy or stereotactic aspiration of cyst are now the preferred choices of management. Awareness of this entity for early diagnosis and management with minimally invasive procedures such as neuroendoscopy or stereotactic aspiration of cyst is crucial for better prognosis and patient care.

Analysis of Giant Intraventricular and Extraventricular Epidermoids, Defining Risk Factors for Recurrence, an Institutional Experience.

BACKGROUND: Multicompartmental intraventricular epidermoids behave differently from multicompartmental extraventricular lesions and localized lesions during its management. Few studies are available which have analyzed risk factors separately in these groups of cases for recurrence of these lesions and time to recur. MATERIALS AND METHODS: In this retrospective observational study, 72 cases of intracranial epidermoid were treated over a span of 7 years. Cases were categorized into three groups. Group 1 comprised 15% (11/72) of cases with intraventricular multicompartmental, Group 2 with 22% (16/72) extraventricular giant tumors with multicompartmental involvement and size >4.5 cm, and Group 3 comprised 63% (45/72) of patients with lesions <4.5 cm and localized. Data pertaining to demography, clinical and radiological features, surgery performed, postoperative complication, histology, and follow-up were obtained from medical records available in the institute. RESULTS: The average duration to treat was 1.86 ± 0.52 (standard deviation [SD]) years, with headache as a major complaint in all the groups. Combined endoscope-assisted microsurgery was performed in 38.8% (28/72), microsurgery in 54.1% (39/72), and endoscopic excision in 6.9% (5/72) of cases. Tumor calcification was found in 23.6% (17/72) and preoperative capsular enhancement was seen in 19.4% (14/72) which persisted in 79% (11/14) of cases postoperatively on subsequent follow-up suggesting recurrence. On stepwise logistic regression analysis, preoperative capsular enhancement was a strong predictor of recurrence of tumor (P = 0.001). The average follow-up was 46 ± 14.92 (SD) months in Group 1, 52.34 ± 11.45 (SD) months in Group 2, and 63.36 ± 18.42 (SD) months in Group 3. CONCLUSION: Although the intracranial epidermoid is known to recur after long interval, tumor with specific characteristics can recur in short span of 5-6 years. Tumor characteristics such as preoperative capsular enhancement, multicompartmental distribution in vertebrobasilar territory, large size, and presence of calcification are strong predictors for recurrence. Performing endoscope-assisted microsurgery can decrease the postoperative morbidities but does not reduce the recurrence risk.

Endoscopic-Assisted Microsurgery for Vestibular Schwannomas: Operative Nuances.

Vestibular schwannoma surgery is a challenging operative procedure. Intricate anatomy of vital neurovascular structures demands a meticulous planning and execution. The cerebellopontine angle is an unforgiving area of skull bases surgery which can have grave implications on patient outcome even after a successful tumor removal. As more and more tumors are being detected at early stage, functional preservation of seventh and eighth nerve complex is increasingly being demanded. The key to any minimally invasive approach is to minimize the collateral damage while ensuring complete tumor removal. Binocular microscopy is the workhorse for illumination and dissection via retrosigmoid approach. However, as instrumentation has improved, endoscopic dissections are increasingly being performed. The following video presents the step-by-step nuances for an endoscope-assisted microsurgery for small vestibular schwannomas with stress on endoscopic drilling of the meatal wall to deliver out intracanacular tumor while preserving the labrynthine structures.

COVID-19 pandemic and safety of taxi services: Looking beyond primary care.

The COVID-19 pandemic is a lifetime experience of 'Living within a pandemic' for the vast majority world over. Public health principles based on equity should be at the core of world's response to it. Service professionals such as taxi/cab drivers are no exception. It is a challenge for them to establish mechanisms for making taxi services safer with regards to SARS COV2 spread, and thereby regain the confidence of stakeholders in this necessary public service. This requires a comprehensive planning taking into account the socio-economic stresses, psychosomatic health and other determinants, and yet being able to adapt and innovate for safer services. These considerations and decisions have to be based on available as well as emerging research evidence about this infection both in the lab and in the community. Targeted safety interventions that translate and apply research findings hold promise. While the course of the pandemic remains uncertain, life must find a 'new normal' and people need to get back to the business of regular living. The purpose of this review is to study the various risks to the stakeholders in taxi/cab services, and draft strategies for mitigating these risks from a theoretical and practical perspective.