Targeting Intracranial Tumours with a Combination of RNA and Chemotherapy.

Glioblastoma multiforme (GBM) is a fast-growing and aggressive brain tumour, which remains largely resistant to treatment; the prognosis for patients is poor, with a median survival time of about 12-18 months, post diagnosis. In an effort to bring more efficacious treatments to patients, we targeted the down regulation of ITCH, an E3 ligase that is overexpressed in a variety of cancers, and which inhibits P73, a tumour suppressor gene. 6-O-glycolchitosan (GC) was used to deliver siRNA ITCH (GC60-siRNA-ITCH) and gemcitabine via the nose to brain route in CD-1 nude mice which had previously been implanted intracranially with U87-MG-luc2 cells. Prior to this in vivo study, an in vitro study established the synergistic effect of siRNA-ITCH in combination with a chemotherapy drug-gemcitabine. A downregulation of ITCH, an upregulation of p73 and enhanced apoptosis were observed in vitro in U87-MG cells, using qPCR, Western blot analysis, confocal laser scanning microscopy, flow cytometry and cytotoxicity assays. When GC60-siRNA-ITCH was combined with gemcitabine, there was a resultant decrease in cell proliferation in vitro. In CD1 mice, the administration of siRNA-ITCH (7 doses of 0.081 mg/kg) alone did not significantly affect animal survival (increasing mean survival from 29 to 33 days when compared to untreated animals), whereas intranasal gemcitabine had a significant effect on survival (increasing survival from 29 to 45 days when compared to untreated animals, p < 0.01). The most significant effect was seen with combination therapy (GC60-siRNA-ITCH plus gemcitabine), where survival increased by 89%, increasing from 29 to 54 days (p < 0.01). Our data demonstrate that siRNA chemosensitises brain tumours to gemcitabine and that the nose-to-brain delivery route may be a viable route for the treatment of intracranial tumours.

Vestibular schwannoma coexisting with dermoid cyst: A case report.

Multiple primary intracranial tumors, or the presence of two or more primary intracranial tumors, are a rare clinical occurrence. The current study presents the case of a 28-year-old patient with concurrent left vestibular schwannoma, left cerebellar hemisphere dermoid cyst and craniovertebral junction malformation, specifically basilar invagination and Klippel-Feil syndrome. The patient exhibited symptoms of torticollis and recurrent headaches, with no apparent hearing loss. A far lateral approach was selected for surgical resection to address these complex conditions and achieve gross total resection in a single-stage surgery while preserving both facial and auditory nerve function. Successful gross total resection was achieved and the function of both nerves was effectively preserved. Of note, the coexistence of vestibular schwannoma and dermoid cyst in the same patient has not been documented in the existing literature. The present study provided a comprehensive account of the presentation and progression of this uncommon medical scenario. Furthermore, a surgical principle for the management of multiple primary intracranial tumors was proposed.

Visual Loss As Primary Manifestation of Olfactory Groove Meningioma.

Differential diagnosis of vision loss in a space-occupying lesion can be exhaustive. Olfactory groove meningioma (OGM) is a rare, benign, slow-growing tumour originating from the anterior cranial base. OGM is one of the differential diagnoses of intracranial tumours. We report a case of an OGM compressing the optic nerve and frontal lobe causing bilateral vision loss for six months. Multidisciplinary management by ophthalmologists, neurosurgeons, radiologists, and pathologists led to the diagnosis and tumour resection of OGM in the patient. Possible mechanisms of vision loss, imaging features, and treatment are discussed in this report.

Ependimoma de fosa posterior en una embarazada: diagnóstico diferencial de una hiperémesis. Reporte de caso / Posterior fossa ependymoma in a pregnant woman: differential diagnosis of hyperemesis. Case report

Resumen ANTECEDENTES: Los tumores intracraneales se diagnostican con una frecuencia muy baja durante el embarazo. Entre los síntomas iniciales destacan: cefalea, náuseas y vómitos frecuentes que, a su vez, son característicos del embarazo, de ahí la necesidad de establecer un diagnóstico diferencial correcto. CASO CLÍNICO: Paciente primigesta, de 25 años, 11+4 semanas de embarazo, con un cuadro de vómitos, cefalea, vértigo e inestabilidad, de inicio subagudo en los últimos dos meses. Antecedentes de interés: cefalea de características tensionales en comparación con migraña crónica no estudiada previamente. Durante la exploración se advirtió enlentecimiento en el lenguaje, nistagmo evocado por la mirada de manera bilateral y dolor periocular izquierdo, junto con vómitos incoercibles que no cedían, pese a la dieta absoluta y administración pautada de metoclopramida y pantoprazol. La resonancia magnética nuclear cerebral con contraste mostró una masa tumoral centrada en el cuarto ventrículo. Con base en lo anterior se procedió a la craniectomía suboccipital con exéresis subtotal del tumor y diagnóstico anatomopatológico de ependimoma de fosa posterior grupo A. Se propuso, y la paciente aceptó, la interrupción del embarazo con el propósito de completar el tratamiento coadyuvante con radioterapia. La intervención quirúrgica le dejó importantes secuelas neurológicas que ameritaron un proceso de rehabilitación. CONCLUSIONES: El momento del diagnóstico es decisivo para indicar el tratamiento de las tumoraciones intracraneales, sobre todo si son de naturaleza maligna, puesto que habrá que establecer un equilibrio entre la salud de la madre y la viabilidad de la gestación. En tanto se trata de pacientes con una afección compleja, su atención médica debe ser multidisciplinaria para disminuir los riesgos para la madre y el feto.

Abstract BACKGROUND: Intracranial tumours are diagnosed very rarely during pregnancy. The initial symptoms include headache, nausea and frequent vomiting, which are characteristic of pregnancy, so a correct differential diagnosis is necessary. CLINICAL CASE: Primigravida patient, 25 years old, 11+4 weeks pregnant, with a history of vomiting, headache, dizziness and instability of subacute onset in the last two months. History of interest: tension-type headache compared with chronic migraine, not previously studied. On examination, slowed speech, bilateral gaze-evoked nystagmus and left periocular pain were noted, together with incoercive vomiting that did not resolve despite a strict diet and prescribed metoclopramide and pantoprazole. A contrast-enhanced MRI of the brain showed a tumour mass centred in the fourth ventricle. Based on the above, a suboccipital craniectomy was performed with subtotal excision of the tumour and anatomopathological diagnosis of group A posterior fossa ependymoma. The interruption of pregnancy was proposed and accepted by the patient to complete the adjuvant treatment with radiotherapy. The surgical intervention left her with significant neurological sequelae that merited rehabilitation. CONCLUSIONS: The time of diagnosis is crucial in the management of intracranial tumours, especially if they are malignant, as a balance must be struck between the health of the mother and the viability of the pregnancy. As these are patients with a complex condition, their medical care must be multidisciplinary in order to reduce the risks to the mother and foetus.

An Unusual Presentation of Spontaneous Rupture of Dermoid Cyst.

Intracranial dermoid cysts are exceptionally rare tumors. Interestingly, this condition has a low mortality rate but a high morbidity rate due to its numerous complications. We report a case of a 62-year-old man who presented with a headache and was found to have a ruptured dermoid cyst, complicated with the dissemination of lipid droplets within the subarachnoid space.

Radiotherapy of benign intracranial tumours.

We present the updated recommendations of the French Society for Radiation Oncology on benign intracranial tumours. Most of them are meningiomas, vestibular schwannomas, pituitary adenomas, craniopharyngiomas, and glomus tumours. Some grow very slowly, and can be observed without specific treatment, especially if they are asymptomatic. Symptomatic or growing tumours are treated by surgery, which is the reference treatment. When surgery is not possible, due to the location of the lesion, or general conditions, radiotherapy can be applied, as it is if there is a postoperative growing residual tumour, or a local relapse. Indications have to be discussed at a multidisciplinary panel, with precise evaluation of the benefit and risks of the treatments. The techniques to be used are the most modern ones, as multimodal imaging and image-guided radiation therapy. Stereotactic treatments, using fractionated or single doses depending on the size or the location of the tumours, are commonly realized, to avoid as much a possible the occurrence of late side effects.

What is the current clinico-radiological diagnostic accuracy for intracranial tumours?

OBJECTIVE: To determine the diagnostic accuracy of routine clinico-radiological workup for a population-based selection of intracranial tumours. METHODS: In this prospective cohort study, we included consecutive adult patients who underwent a primary surgical intervention for a suspected intracranial tumour between 2015 and 2019 at a single-neurosurgical centre. The treating team estimated the expected diagnosis prior to surgery using predefined groups. The expected diagnosis was compared to final histopathology and the accuracy of preoperative clinico-radiological diagnosis (sensitivity, specificity, positive and negative predictive values) was calculated. RESULTS: 392 patients were included in the data analysis, of whom 319 underwent a primary surgical resection and 73 were operated with a diagnostic biopsy only. The diagnostic accuracy varied between different tumour types. The overall sensitivity, specificity and diagnostic mismatch rate of clinico-radiological diagnosis was 85.8%, 97.7% and 4.0%, respectively. For gliomas (including differentiation between low-grade and high-grade gliomas), the same diagnostic accuracy measures were found to be 82.2%, 97.2% and 5.6%, respectively. The most common diagnostic mismatch was between low-grade gliomas, high-grade gliomas and metastases. Accuracy of 90.2% was achieved for differentiation between diffuse low-grade gliomas and high-grade gliomas. CONCLUSIONS: The current accuracy of a preoperative clinico-radiological diagnosis of brain tumours is high. Future non-invasive diagnostic methods need to outperform our results in order to add much value in a routine clinical setting in unselected patients.

Norman Dott (1897-1973) and medical illustration: the importance of art to neurosurgery.

Anatomical information and pathologies have been conveyed through the medium of medical illustrations for centuries. In the formative years of British neurosurgery, Professor Norman Dott (1897-1973) utilised medical illustrations as a means of documenting neurosurgical advances and conveying pathological-anatomical correlation. He commissioned a vast number of medical illustrations over the course of his career, ultimately producing a diverse collection of items, most of which is cared for by Lothian Health Services Archive (LHSA), Edinburgh, Scotland. In this study, the original material from Dott's personal collection was audited. Of 172 stand-alone drawings, 84 were categorised and analysed. The findings are a reflection of Dott's expertise as an academic and a surgeon. Spanning the years 1925-1968, a wide range of pathologies and procedures are depicted including intracranial aneurysms and their ligation, an area in which Dott was renowned for pioneering surgical advances. The collection stands as a testament to Dott's emphasis upon medical illustration to communicate the intricacies and complexities of his field, providing valuable insight into clinical and surgical practice in neurosurgery when the specialty was in its juvenescence. In order to illuminate the connections between biography and specialism that generated an extraordinary visual archive, this study considers the early life and work of Norman Dott and the influence of Harvey Cushing on Dott's prioritisation of visual documentation of surgical practice. It explores the impact of German-American medical artist Max Brödel on the UK, and especially on the artists employed by Dott, before presenting a short review of the medical illustrations they created.

Pattern of intracranial tumours in a tertiary hospital in Ghana.

OBJECTIVE: This study seeks to describe the pattern of intracranial tumours in Korle Bu Teaching Hospital (KBTH) based on patient demographics, clinical presentation, spatial distribution of tumour and histological findings. METHOD: The study design is retrospective and descriptive. Data was obtained from the clinical records of patients with intracranial tumours treated in our neurosurgery unit between January 2010 to December 2015, and histology reports obtained from the histopathology unit. Patients with intracranial tumours without definitive histological diagnosis were excluded. RESULTS: Of the 102 histologically diagnosed brain tumours, out of 335 brain tumour cases seen in the period under review, 58 (56.9%) were females and 44 (43.1%) were males (p = 0.031). Gliomas were the commonest intracranial tumours - 39(38.2%) followed by Meningiomas 37(36.2%) and Pituitary Adenoma - 9(8.8%). Astrocytoma was the commonest type of Glioma comprising 30(77%) of the 39 cases. Meningotheliomatous meningioma was the commonest type of meningioma with 11 (29.7%) of 37 cases. Of the 39 Gliomas 17(43.6%) were males and 22(56.4%) were females, while for the Meningioma 17(46%) were males and 20(54%) were females. The commonest symptom was headache (64%) and the commonest tumour location was supratentorial (77.5%). The crude incidence rate of intracranial tumours in this study was 1.34 per 100,000 populations per year. CONCLUSION: Gliomas are the commonest intracranial tumours seen in our series. Overall, females were more commonly affected than males in most brain tumours in this series, including both gliomas and meningiomas. FUNDING: Not declared.

Mature teratoma of the pineal region in the paediatric age group: A case report and review of the literature

@#Introduction: Intracranial teratomas account for 0.5% of all intracranial tumours and 2-4% of intracranial tumours in children. However, in terms of tumours of the pineal area, the exact incidence is not ascertained. Although, it is noted that 50-60% of central nervous system (CNS) germ cell tumours are found in the pineal gland. The degree of difficulty in the sampling of lesions in the pineal gland during biopsy emphasizes the importance of correlating the imaging studies, histopathologic findings, and serum and cerebrospinal fluid (CSF) tumour markers. Case Report: This case report is that of a 9-year-old male who presented with frontal headache of eight days, with associated photophobia, nausea and vomiting, and diplopia. Biopsy with intraoperative navigation was done and the specimen was referred for histopathologic evaluation. The biopsy showed findings consistent with a mature teratoma with no histologic findings of an immature component or secondary somatic malignancy. Comparison of the pre-operative and post-operative multiaxial cranial CT scan showed findings that was consistent with a residual lesion. This was correlated with the pre-operative serum tumour markers which showed alpha-fetoprotein of 22.5 ng/mL and beta-HCG of 1.0 mIU/mL(IU/L), and the post-operative tumour markers of the cerebrospinal fluid that showed alpha-fetoprotein of 3.28 ng/mL and beta-HCG of 18.9 mIU/mL (IU/L). Conclusion: A review of the literature and comparison with current case in relation to the histopathologic, serum and CSF findings, and imaging studies was done to better understand the mechanism of this lesion.

Treatment Outcome in Patients with Primary Central Nervous System Germ Cell Tumour: Clinical Experience from a Regional Cancer Centre in North India.

BACKGROUND: Primary intracranial germ cell tumour is a rare entity and constitutes 2-3% of all paediatric brain tumours in Western countries. We herein intend to report the clinical features and treatment outcome of patients with primary central nervous system germ cell tumour treated at our institute. METHODS: Clinical data were collected by retrospective chart review from 2006 to 2012. Histopathology slides were reviewed and relevant immunohistochemistry stains were done. Overall survival (OS) and progression-free survival (PFS) were analysed by the Kaplan-Meier product-limit method. RESULTS: Twenty patients met the study criterion (male:female = 7:3). Median age at presentation was 13 years. Tumour location was pineal in 10 patients, suprasellar in 6, thalamic in 2, basal ganglion in 1, and spinal in 1. Leptomeningeal spread was noted in 1 patient at presentation. Surgical resection was gross-total in 7 patients (35%), near-total in 2 (10%), subtotal in 4 (20%), and limited to biopsy in 6 (30%). The tumours were germinomatous, non-germinomatous, and of mixed germ cell subtype in 17 patients (85%), 2 patients (10%), and 1 patient (5%), respectively. Systemic chemotherapy (median of 4 cycles) was given to 19 patients (95%). The common regimens used were a combination of bleomycin, etoposide and cisplatin (BEP) in 14 patients (70%) and etoposide and cisplatin (EP) in 5 patients (25%). Radiation therapy (40-50 Gy in conventional fractionation; median of 42 Gy) was delivered to 17 patients (85%): local radiation in 6 and whole ventricular, whole brain, and craniospinal irradiation followed by a boost in 5, 3, and 3 patients, respectively. After a median follow-up of 44.52 months, 17 patients (85%) were in complete response and 3 (15%) had progressive disease. Death and disease recurrence were noted in 6 patients (30%) and 1 patient, respectively. Median OS and PFS were not reached. The actuarial rates of OS at 3 and 5 years were 75.8 and 68.9%, respectively. The actuarial rates of PFS at both 3 and 5 years were 81.6%. CONCLUSION: Multimodality treatment consisting of limited resection followed by platinum-based systemic chemotherapy and radiotherapy (40-50 Gy) is a reasonable treatment strategy in patients of primary central nervous system germ cell tumour in a developing nation.

Esthesioneuroblastomas: Reservations and Recommendations.

Neuroectodermal tumour has a wide range of biological activity that ranges from an indolent course to local recurrence and rapid widespread metastasis. We describe, herewith, 2 patients with Esthesioneuroblastomas (ENB) who had varied atypical clinical presentation. The first case presented with Intracranial Pressure (ICP) headache and acute visual deterioration with radiology revealing an extra axial lesion with extension into the nasal cavity while the second case presented with nasal congestion and progressive headache of long duration. We review the unusual characteristics that may uncommonly occur in ENBs and elaborate regarding which of these must be considered when evaluating patients with this malignancy.

Histopathological and Immunohistochemical Evaluation of Meningiomas with Reference to Proliferative Markers p53 and Ki-67.

INTRODUCTION: Meningiomas are slow growing primary central nervous system (CNS) tumours attached to the duramater, which arise from the meningothelial cells of the arachnoid. Grading of meningioma based on histological findings assisted with supplementary immunohistochemical studies, predicts the prognosis of meningioma with good precision. AIM: To evaluate proliferative markers and correlate with various histological subtypes and grade. MATERIALS AND METHODS: A total of 224 meningiomas, diagnosed between January1995 and October 2011were graded according to WHO 2007 criteria. Immunostaining for p53 and Ki-67 markers were performed on 100 cases. RESULTS: There was female predominance. There were 194 Grade I, 24 Grade II and 6 Grade III meningiomas. Brain invasion noted in 18(8%) meningiomas predominantly in grade III followed by grade II. Recurrence was seen in 7 (3.1%) cases, most common in psammomatous followed by angiomatous meningioma. Immunostaining showed p53 positivity in 72.5% of grade I, 83.3% of grade II and all the cases of grade III tumours. Ki-67 Labelling Index (LI) consistently increased from grade I to grade III tumours. CONCLUSION: p53 and Ki-67 LI correlated well with increasing histological grade and biological behaviour of meningioma.

Human cytomegalovirus and primary intracranial tumours: frequency of tumour infection and lack of correlation with systemic immune anti-viral responses.

AIMS: Human cytomegalovirus (HCMV) is a ubiquitous beta human herpesvirus able to influence infected cell survival and proliferation and to modulate the host immune response. As there is accumulating evidence that HCMV is detected in primary intracranial astrocytic tumours, in this study we looked for the presence of HCMV in intracranial tumours and tried to correlate this eventual presence with the anti-HCMV systemic immunoreactivity and with the detection of HCMV in peripheral blood. METHODS: In this study, we analysed 43 glioblastomas (GBM), 14 oligodendrogliomas (OL) and 20 meningiomas (MG) by immunofluorescence (IF) targeting HCMV immediate early antigen (IE1) and by nested PCR (nPCR) amplifying HCMV glycoprotein B (gB). RESULTS: Detection of IE1 by IF showed the presence of HCMV in 70% of GBM, 57% of OL and 85% of MG, in contrast to gB nPCR, which detected HCMV in only 50% of GBM, 38% of OL and 46% of MG. Unexpectedly, HCMV DNA and antigens were detected within GBM, OL and MG of patients that exhibit negative viral serology. More surprisingly, PCR on the peripheral blood did not detect HCMV in patients with a HCMV-positive tumour. CONCLUSIONS: Our results are in agreement with previous observations demonstrating HCMV in glial tumours and highlight the presence of HCMV in meningiomas. We also showed that anti-HCMV specific systemic immunoreactivity and detection of HCMV in peripheral blood are not predictive of HCMV presence in primary intracranial tumours.

Computerised Tomography Features in Gliomas.

106 cases of intracranial tumours were evaluated, out of which 42 cases (39.6%) were histologically confirmed as gliomas. Computerised tomography (CT) imaging characteristics of glioma were studied with respect to morphology and contrast enhancement to find a possible correlation between CT appearance and the grade of malignancy. It was found that there is a range of patterns both before and after intravenous contrast, which allows an assessment of grading of the tumour with a fair degree of reliability.