Mammalian target of rapamycin inhibitors, temsirolimus and torin 1, attenuate stemness-associated properties and expression of mesenchymal markers promoted by phorbol-myristate-acetate and oncostatin-M in glioblastoma cells.

The phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling pathway is crucial for tumor survival, proliferation, and progression, making it an attractive target for therapeutic intervention. In glioblastoma, activated mammalian target of rapamycin promotes invasive phenotype and correlates with poor patient survival. A wide range of mammalian target of rapamycin inhibitors are currently being evaluated for cytotoxicity and anti-proliferative activity in various tumor types but are not explored sufficiently for controlling tumor invasion and recurrence. We recently reported that mammalian target of rapamycin inhibitors-rapamycin, temsirolimus, torin 1, and PP242-suppressed invasion and migration promoted by tumor necrosis factor-alpha and phorbol-myristate-acetate in glioblastoma cells. As aggressive invasion and migration of tumors are associated with mesenchymal and stem-like cell properties, this study aimed to examine the effect of mammalian target of rapamycin inhibitors on these features in glioblastoma cells. We demonstrate that temsirolimus and torin 1 effectively reduced the constitutive as well as phorbol-myristate-acetate/oncostatin-M-induced expression of mesenchymal markers (fibronectin, vimentin, and YKL40) and neural stem cell markers (Sox2, Oct4, nestin, and mushashi1). The inhibitors significantly abrogated the neurosphere-forming capacity induced by phorbol-myristate-acetate and oncostatin-M. Furthermore, we demonstrate that the drugs dephosphorylated signal transducer and activator transcription factor 3, a major regulator of mesenchymal and neural stem cell markers implicating the role of signal transducer and activator transcription factor 3 in the inhibitory action of these drugs. The findings demonstrate the potential of mammalian target of rapamycin inhibitors as "stemness-inhibiting drugs" and a promising therapeutic approach to target glioma stem cells.

HIV associated Burkitt's lymphoma.

Burkitt's lymphoma (BL) is a highly aggressive B-cell non-Hodgkin Lymphoma (NHL) associated with chromosomal translocations resulting in upregulation of the proto-oncogene C-MYC, which drives progression through the cell cycle NHL accounts for approximately one third of AIDS-related malignancies and the frequency of BL is 2.4-20% of HIV-associated NHL. The outcome of HIV-associated non-Hodgkin lymphoma (NHL) has improved substantially in the highly active antiretroviral therapy (HAART) era. However, HIV-Burkitt lymphoma (BL), which accounts for up to 20% of HIV-NHL, still has poor outcome with standard chemotherapy. We present here a 26 years old female who presented with congestive cardiac failure and sudden onset paraparesis and was finally diagnosed to have right atrial mass and had extradural lesion extending from L2 to S1 which turned out to be High grade NHL-Burkitt's Lymphoma.

Endoscopic Transnasal Navigation Guided Treatment of Clivus Abscess in Adult with Mucormycosis: A Rare Report.

Osteomyelitis and abscess of the clivus are rare conditions thought to arise from contiguous spread of infection from the paranasal sinuses. Clival osteomyelitis is a rare potentially life-threatening skull base infection which is generally challenging to diagnose and treat. It is typically seen in the pediatric population and is very rare in the adult population. The exact pathophysiology of osteomyelitis of the clivus is relatively uncertain. Here, we describe a case of a 32-year-old immunocompetent female with a primary complaint of headache, with no significant medical history of diabetes, hypertension or rhinosinusitis or SARS COV-2 for the past 18 months. This case report demonstrates an image-guided and endoscopic approach to surgical localization and treatment of abscesses in the clival area.

Pituitary Apoplexy Presenting with Isolated Third Nerve Palsy: A Rare Case Report.

A 46-year-old female came to neurosurgery outpatient department with sudden onset of drooping of RE upper eyelid and restriction of movements in adduction, depression and elevation in right eye. Patient was a known case of diabetes mellitus whose blood sugar levels were deranged. On examination, patient was diagnosed pituitary macroadenoma. Patient was treated for her uncontrolled diabetes mellitus following which she had underwent transsphenoidal pituitary macroadenoma removal. On treatment, patient's ptosis had subsided and restriction of movement has resolved.

A rare case of subependymal giant cell astrocytoma presenting with spontaneous intratumoral hemorrhage.

ABSTRACT: Subependymal giant cell astrocytomas (SEGAs) are low-grade gliomas usually arising in the periventricular regions near the foramen of Monro seen exclusively with tuberous sclerosis complex. Incidence of hemorrhage in SEGA is less than 1% with only 10 cases reported in English literature. We present a similar case of SEGA with spontaneous intratumoral hemorrhage in a 35-year-old male with cutaneous manifestations of tuberous sclerosis complex and acute onset headache with convulsion.

Orbital Cholesterol Granuloma : A Rare Case Report.

Cholesterol Granuloma is a rare lesion which occurs at locations like ear, peritoneum, lungs, breast etc. and formed due to interaction of Cholesterol and living tissue. But Cholesterol Granuloma occurring in the orbit is a very rare entity and so we authors present a case of Cholesterol Granuloma of the orbit.

Histopathological Spectrum of Gliomas and Its Immunohistochemical Correlation in a Tertiary Care Setup.

Introduction Central nervous system (CNS) tumors pose significant diagnostic challenges due to their varied morphological and differentiating characteristics. Modern advancements in immunohistochemistry (IHC) and molecular pathology have greatly enhanced prognostication, screening, and therapeutic management. Gliomas, a type of tumor originating from glial cells in the CNS, can develop from astrocytes, oligodendrocytes, or ependymal cells. According to the 2021 update, the classification of diffuse gliomas is primarily based on the presence or absence of isocitrate dehydrogenase (IDH1/2) mutations. IDH-wildtype gliomas (glioblastomas) have a significantly poorer prognosis compared to IDH-mutant gliomas (astrocytomas and oligodendrogliomas). Gliomas are highly infiltrative and resistant to treatment, making them largely incurable regardless of their grade and prognosis. Objective This study aimed to determine the histopathological diversity of gliomas and its correlation with protein expressions of IDH, ATRX gene (α-thalassemia/mental retardation syndrome X-linked), Ki-67, and p53 mutations (tumor suppressor gene-53), according to the 2021 World Health Organization (WHO) Classification of CNS Tumors, Fifth Edition. Methods This descriptive cross-sectional study was carried out in the Department of Pathology at a tertiary care center, focusing on various types of gliomas received over a two-year period. A total of 54 specimens of gliomas received from the Department of Neurosurgery were subjected to histopathological examination. Sections were stained using hematoxylin and eosin (H&E), and IHC was performed using four markers (IDH, ATRX, p53, Ki-67) in each case. Results were analyzed according to the 2021 WHO Classification of CNS Tumors, Fifth Edition. Results The majority of individuals were between the age group of 40 and 60 years, showing a male predominance (65%). The most common site was the frontal lobe. Glioblastoma constituted the largest proportion (46.2%) of the total cases, followed by astrocytoma (20.3%), oligodendroglioma (18.5%), pilocytic astrocytoma (7.4%), and ependymoma (7.4%). All 11 cases of astrocytoma exhibited IDH mutation and ATRX loss, with p53 positive in the majority of cases. Strong nuclear p53 immunohistochemical positivity in >10% of tumor nuclei correlates with TP53 mutations. Among 25 cases of glioblastoma, IDH was negative, ATRX was retained in all cases, and 11 cases were positive for p53 mutation. For oligodendroglioma, out of 10 cases, IDH mutation was positive, and ATRX was retained in all cases. p53 mutation was not seen in any case. All cases of pilocytic astrocytoma were negative for IDH and p53 mutations, with ATRX retained in all cases. In all cases of ependymoma, IDH and p53 mutations were negative, and ATRX was retained in all cases. Glioblastomas exhibited the highest Ki-67 expression. Conclusion The 2021 WHO Classification of CNS Tumors, Fifth Edition, was updated, building on previously established concepts and continuing to evolve. The final diagnosis of gliomas relies on a comprehensive combination of clinical evaluation, neuroimaging, pathological examination, and molecular analysis. Nonetheless, histopathological examination, along with IHC, remains the cornerstone of diagnosis.

Epidermoid Cyst of the Brainstem in 3-Year-Old Child: A Rare Case Report.

Epidermoid cysts are infrequent lesions occupying the intracranial space, comprising approximately 1-2% of all intracranial tumors. Brainstem epidermoids are exceptionally uncommon in children; up until now, only a few scattered case reports have been documented in the literature regarding this unique location. These cysts commonly arise from the inclusion of ectodermal elements during neural tube closure. Complete excision of these cysts is challenging due to their close proximity and adherence to the brainstem, which makes it difficult to achieve. As a result, recurrence of the cysts is not uncommon. We have reported a rare case of a 3-year-old with a 5-month history of progressive headache, imbalance while walking and progressive weakness in his right upper limb and lower limb along with difficulty in swallowing. On MRI Brain imaging study he had a pre-pontine epidermoid with intra-axial extension in the pons. The patient underwent retro-sigmoid/suboccipital craniotomy and microsurgical excision of the tumor, including the tumor capsule. After completing the surgery, the cavity was irrigated using a solution containing hydrocortisone and Ringer lactate to prevent the occurrence of aseptic meningitis. In the postoperative, the patient recovered without any complications, as all symptoms showed immediate improvement, and the lower cranial nerves returned to normal functioning.

Pilomyxoid Astrocytoma Presenting With Developmental Regression: A Case Report.

Pilomyxoid astrocytoma (PMA) is a subtype of pilocytic astrocytoma (PA). PMA tends to exhibit a more aggressive course compared to PA. We present a case of a two-year-old male with a PMA in the suprasellar region who presented with developmental regression, loss of previously attained milestones such as the ability to hold his neck, walk, and talk, along with hypotonia in all four limbs. Serum cortisol and thyroid-stimulating hormone (TSH) levels were measured to rule out endocrine disturbances and were within normal limits. Magnetic resonance imaging (MRI) of the brain showed a solid lesion in the suprasellar region, extending into the pituitary and interpeduncular fossae, compressing the pituitary gland, and effacing the third ventricle, causing cerebrospinal fluid (CSF) flow obstruction and lateral ventricle dilation. The tumor appears hypointense on T1 and hyperintense on T2, with fluid-attenuated inversion recovery (FLAIR), peripheral contrast enhancement, and no calcification, consistent with PMA. The CSF analysis was negative for malignant cells. Histopathological examination revealed monomorphous bipolar and spindle cells in an angiocentric pattern with a myxoid background, without rosenthal fibers, mitoses, or eosinophilic granular bodies, consistent with PMA but not seen in PA. Immunohistochemistry showed strong positivity for glial fibrillary acidic protein (GFAP) and S100, with a Ki-67 index of 3-4%, indicating a low-grade tumor. The preferred treatment is surgical resection, but due to the tumor's deep location and potential long-term neurological effects, the parents opted against surgery. A ventriculoperitoneal shunt was placed to alleviate CSF flow, following which the child showed mild improvement in symptoms. Treatment of nonresectable astrocytomas was controversial, but gross total surgical resection offers better disease control. Chemotherapy is for patients with recurrence or where total resection of the tumor is not possible, and radiotherapy, though the long-term disease control is good, has a variable visual outcome.

Immediate postoperative resolution of syrinx post-C1/C2 fixation in an operated case of foramen magnum decompression for Chiari malformation: Is Goel's procedure a rescue surgery or a gold standard?

Chiari malformation (CM) is a common neurological disorder with foramen magnum decompression (FMD) as a commonly accepted treatment. The authors present a case of CM-1 wherein there was no radiological instability preoperatively and FMD was done as a treatment, after which the patient improved transiently only to deteriorate further. Atlantoaxial fixation was done as a second-stage procedure, after which the patient improved clinically and radiologically. The knowledge of this case and surgical entity should be borne in mind before the formulation of a treatment plan. It is important that the solution is to identify and treat the underlying pathology rather than to decompress and directly manipulate the tonsils.

Single-level ossified ligamentum flavum causing a holocord syrinx: illustrative case.

BACKGROUND: Syringomyelia is a neurological disorder that is caused by abnormal cerebrospinal fluid flow or circulation. It is an incidental finding in most cases, predominantly presenting with sensory symptoms of insensitivity to pain and temperature. Spinal ossified ligamentum flavum (OLF) leading to syringomyelia is one of the rare causes. The authors report an unusual case of syringomyelia due to a thoracic OLF. OBSERVATIONS: A 54-year-old female presented with backache, difficulty walking, spasticity in the bilateral lower limbs, tingling sensation in the bilateral lower limbs, and paraparesis for 5 years. Her radiological investigations were suggestive of an OLF causing a syrinx. She underwent laminectomy, and her syrinx resolved on subsequent follow-up. LESSONS: A syrinx due to a single-level OLF is rare, and this uncommon cause should be kept in mind while formulating treatment plans.

Post Mucormycosis Frontal Bone Osteonecrosis: "A Road Less Traveled During the Pandemic".

BACKGROUND: Osteonecrosis in mucormycosis is a rare phenomenon and has been reported usually following trauma or in immunocompromised individuals. Osteonecrosis of skull as a complication of mucormycosis is a rare presentation, which makes the study ever so rare and interesting. METHODS: Within 6 months, a total of 114 patients presented with mucormycosis as COVID-19 sequel, 60 of whom underwent form of endoscopic sinus debridement. Six of these 60 patients presented with frontal bone osteonecrosis and were included in the study. All 6 patients presented within a time period of 2-4 months' post FESS. RESULTS: One of the 6 patients succumbed to her illness. Another patient presented with local recurrence after 3 months, for which she underwent resurgery and debridement. The other 4 patients showed gradual recovery and are without symptoms or radiologic progression at 6-month follow-up. CONCLUSIONS: Osteonecrosis in mucormycosis is a rare phenomenon, and the 2 entities have rarely been reported together. The disease usually limits itself to the frontal bone only, and pathogenesis for spread is due to a vicious cycle of infection and ischemia. Prompt diagnosis via imaging, aggressive surgical debridement with a good antifungal cover, good patient compliance, and regular follow-up form the mainstay of treatment.

Unusual Presentation of Osteoid Osteoma of the Cervical Spine with Dysphagia: A Case Report.

It is uncommon for bony cervical spine lesions to cause dysphagia. Middle-aged female presented in the outpatient clinic with complaints of dysphagia of insidious onset. Patient's medical history, clinical manifestation and imaging studies guided the diagnosis of spinal osteoid osteoma. The presentation and surgical management are discussed in this report. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03835-w.

Piecing Together a Puzzle of Exceptional Lesions: A Retrospective Study of a Potpourri of 160 Space-Occupying Lesions of the Central Nervous System.

Introduction Central nervous system (CNS) lesions are rare and histologically heterogenous, and carry serious potential for patient morbidity and mortality. A retrospective epidemiological review of CNS neoplasms is of great importance for future research because it can demonstrate the changes in the spectrum of CNS lesions of a population, unveil the possible associated risk factors, and indicate the potential therapeutic methods for various neoplastic and non-neoplastic lesions. Neurosurgeons have always shown an obsession with a good neuropathological diagnosis in intracranial and extracranial lesions. This obsession need not be overemphasized as it helps the clinician plan an adequate surgical/treatment strategy to optimize outcomes and minimize morbidity. Methods This study included a spectrum of 160 biopsies of patients with space-occupying lesions of the CNS during a period of two years (2019-2021). All the cases were studied and analyzed, and their histological typing/grading was done. The cases were graded and categorized according to the 2016 WHO Classification of CNS Tumors. Results Among 160 cases, the study showed a slight male preponderance of 100 (62.5%) cases. The maximum number of cases, 37 (23%) cases, was in the age group of 41-50 years. Clinically, the commonest complaints were headache and seizures. The most common location of tumor was supra-tentorial, comprising around 96 (60%) cases, of which 27 (28%) cases were located in the frontal lobe. There were four (2.5%) cases that had non-neoplastic lesions and the rest 156 (97.5%) cases had neoplastic lesions. Malignant lesions outnumbered the benign lesions, comprising of 82 (51.25%) cases. Among the neoplastic lesions, the highest cases were of astrocytoma, 48 (30.76%) cases, followed by meningioma, 42 (26.92%) cases. Also, 21 extremely rare and unusual cases were encountered. Conclusion The present study reflects the diversity of histopathological spectrum of CNS lesions in our center. In-depth studies from across various hospitals are required to have representative data on the incidence, epidemiological profile, and etiology of CNS lesions in India.

Contrecoup Extradural Hematoma: When Hematomas Do Not Follow Rules.

Extradural hematoma (EDH) is a fairly common entity in neurosurgical practice but EDHt at a contrecoup site and crossing a cranial suture is rare. The authors present a case of EDH due to contrecoup injury in whom sutural diastases was noted and hematoma was seen to be crossing the adjacent suture. This was accompanied with subdural hematoma (SDH) at the coup site. According to the best of our knowledge, it makes the case only the 13th such to be reported in adults. A 27-year-old male patient was brought by relatives with a history of fall from a height resulting in head trauma over the left posterior parietal region. The patient presented with headache at the site of impact. Computed tomography (CT) scan of the brain revealed an undisplaced fracture of parietal bone on the left side (coup site) along with a small concavo-convex hyperdense lesion suggestive of a SDH. Scan also revealed a large biconvex, hyperdense lesion in the right frontoparietal region (contrecoup site). The hematoma was seen to be evidently crossing the coronal suture. Sutural diastases of coronal suture was suspected and the same was noticed intraoperatively. Approximately 80cc of clot was removed and hemostasis was achieved through coagulation of the middle meningeal artery and via dural hitch sutures. Contrecoup EDH across the adjacent suture with sutural diastases is rare as it does not follow the set rules of hematomas. A high index of suspicion is central in arriving at a rapid diagnosis and an early surgery to achieve a favorable outcome. The authors recommend a CT scan along all three planes along with a three-dimensional reconstruction for ready diagnosis. Contrecoup EDH with sutural diastases is a distinct and potentially dangerous entity and neurosurgeons should be aware of the same.

Giant Cell Tumour Of The Occipital Bone In A 13-Year Old Male.

Giant Cell Tumours (GCT) are usually found at the extremities of the long bones and their presence in the skull being less than 1%. In the skull, sphenoidal bone and temporal bone are the commonest sites. There have been very few reports of GCTs of the occipital bone. Total excision surgery is the ideal treatment of choice. If surgery poses a problem, then adjuvant radiotherapy can be administered too. We present a case of 13-year-old male child who was diagnosed with GCT of the occipital bone. He was successfully operated and is symptom free 6 months post his surgery till now.

Neuro-Ophthalmic Manifestations of Intracranial Space Occupying Lesions in Adults.

Objectives: The purpose of this study is to evaluate the epidemiology, neuro-ophthalmic, and clinical characteristics of intracranial space occupying lesions (ICSOLs) in adult patients. Methods: All patients above 16 years presenting with brain tumors confirmed by magnetic resonance imaging and treated surgically in our institute were included in this study. Epidemiology of the patients along with neurological and ophthalmic manifestation was evaluated. Results: A total of 252 patients were included in the study ranging from 18 years to 79 years. Supratentorial location was more common than infratentorial location. The most common neurological symptom in our study was headache followed by seizures. Ophthalmic manifestations were present in (73.4%) of patients. The most common visual symptoms and signs were visual loss, strabismus, papilledema, and visual field defects. The most common histopathological diagnosis seen in our study was meningiomas followed by high-grade gliomas. Conclusion: Ocular signs and symptoms can be considered as a window to the brain through which ICSOLs can be detected. The most common neurological manifestation of ICSOL in our study was headache with or without true localizing signs and symptoms. More frequently, these patients present to an ophthalmologist before a neurosurgeon with related ocular manifestations. Hence, through our study, we emphasize the importance of a detailed ophthalmological examination in these patients which can aid in early diagnosis and prompt management of such lesions.

Cirsoid Aneurysm of Occipital Artery-Rare of the Rarest.

A case of 33 year old man diagnosed with a rare case of Cirsoid aneurysm of occipital artery was treated under general anaesthesia for surgical excision. An interdisciplinary approach of Neurosurgery and Oral and Maxillofacial team was made. Here we have discussed the clinical steps performed in the management of Cirsoid aneurysm of occipital artery. In-toto excision and thorough follow up has uneventfully lead to success in the outcome.

Prostate Apoptosis Response-4 (Par-4): A Novel Target in Pyronaridine-Induced Apoptosis in Glioblastoma (GBM) Cells.

Glioblastoma (GBM) is an aggressive form of brain tumor with a median survival of approximately 12 months. With no new drugs in the last few decades and limited success in clinics for known therapies, drug repurposing is an attractive choice for its treatment. Here, we examined the efficacy of pyronaridine (PYR), an anti-malarial drug in GBM cells. PYR induced anti-proliferative activity in GBM cells with IC50 ranging from 1.16 to 6.82 µM. Synergistic activity was observed when PYR was combined with Doxorubicin and Ritonavir. Mechanistically, PYR triggered mitochondrial membrane depolarization and enhanced the ROS levels causing caspase-3 mediated apoptosis. PYR significantly decreased markers associated with proliferation, EMT, hypoxia, and stemness and upregulated the expression of E-cadherin. Interestingly, PYR induced the expression of intracellular as well as secretory Par-4, a tumor suppressor in GBM cells, which was confirmed using siRNA. Notably, Par-4 levels in plasma samples of GBM patients were significantly lower than normal healthy volunteers. Thus, our study demonstrates for the first time that PYR can be repurposed against GBM with a novel mechanism of action involving Par-4. Herewith, we discuss the role of upregulated Par-4 in a highly interconnected signaling network thereby advocating its importance as a therapeutic target.

Neuroophthalmic Manifestations of Intracranial Tumours in Children.

BACKGROUND: All children between 0 and 16 years presenting with brain tumours confirmed by Magnetic Resonance Imaging (MRI) and treated surgically in our institute were included in this study. OBJECTIVE: The aim of this study is to evaluate the neuroophthalmic and clinical characteristics of intracranial space occupying lesions in children. METHODS: Neuroophthalmic manifestations along with location of the tumour by contrast-enhanced MRI, type of surgical intervention, and postoperative histopathological diagnosis were evaluated. RESULTS: In pediatric brain tumours, male preponderance was seen and supratentorial location was more common in general, while in older children, infratentorial tumours were more common than supratentorial tumours. Headache, vomiting, and cerebellar signs were the commonest neurological features. Diminution of vision, diplopia, and strabismus were the commonest ophthalmic symptoms. Papilledema, ophthalmoparesis, and nystagmus were the most frequent ophthalmological signs. Neurological manifestations of seizures, altered sensorium and motor deficits were more frequently seen in supratentorial tumours, while cranial nerve involvement and ataxia were seen in infratentorial tumours. Ophthalmological manifestations including diplopia, strabismus, ophthalmoparesis, and nystagmus were more frequently seen in infratentorial tumours. Astrocytoma was the most frequent histopathological diagnosis followed by medulloblastoma. CONCLUSION: Diagnosis of pediatric intracranial tumours is complex and requires a multidisciplinary approach for prompt management. An ophthalmologist should have a high index of suspicion for brain tumours especially in patients presenting with common ocular symptoms like diminution of vision, diplopia, and strabismus without any neurological symptoms.