Bifurcation dissecting aneurysm: tips and tricks to differentiate from saccular aneurysm.

Bifurcations are a common site for saccular aneurysms, but rarely can be a site for dissecting aneurysms. Identification of these aneurysms is extremely important because the management plan depends on it. We describe a rare case of a ruptured dissecting aneurysm at the right ICA bifurcation in a pre-teen child which posed a diagnostic dilemma but ultimately was successfully managed with flow diversion.

COVID-19 associated multisystemic mucormycosis from India: a multicentric retrospective study on clinical profile, predisposing factors, cumulative mortality and factors affecting outcome.

PURPOSE: The clinical course of COVID-19 has been complicated by secondary infections, including bacterial and fungal infections. The rapid rise in the incidence of invasive mucormycosis in these patients is very much concerning. COVID-19-associated mucormycosis was detected in huge numbers during the second wave of the COVID-19 pandemic in India, with several predisposing factors indicated in its pathogenesis. This study aimed to evaluate the epidemiology, predisposing factor, cumulative mortality and factors affecting outcomes among the coronavirus disease COVID-19-associated mucormycosis (CAM). METHODS: A multicenter retrospective study across three tertiary health care centers in Southern part of India was conducted during April-June 2021. RESULTS: Among the 217 cases of CAM, mucormycosis affecting the nasal sinuses was the commonest, affecting 95 (44%) of the patients, orbital extension seen in 84 (38%), pulmonary (n = 25, 12%), gastrointestinal (n = 6, 3%), isolated cerebral (n = 2) and disseminated mucormycosis (n = 2). Diabetes mellitus, high-dose systemic steroids were the most common underlying disease among CAM patients. The mucormycosis-associated case-fatality at 6 weeks was 14%, cerebral or GI or disseminated mucormycosis had 9 times higher risk of death compared to other locations. Extensive surgical debridement along with sequential antifungal drug treatment improved the survival in mucormycosis patients. CONCLUSION: Judicious and appropriate management of the predisposing factor and factors affecting mortality associated with CAM with multi-disciplinary approach and timely surgical and medical management can be much helpful in achieving a successful outcome.

Reporting a Case of Cervical Vertebral Body Primary Malignant Melanoma-A Rare Entity.

Melanomas of vertebral body are usually metastatic lesions. Isolated vertebral body melanomas are rare may be due to unknown primary. Only threesuch cases havebeen reported in literature. We are reporting a 30-year-old female presented with progressive quadriparesis and bladder involvement. On evaluation, an extradural lesion at the C4-5 level with the destruction of C4 vertebral body and anterior in the prevertebral space seen with areas of blooming. The patient underwent surgery and biopsy was suggestive of melanoma. On further evaluation, we could find any other lesion in the body. The lesion can be either metastatic with unknown primary or primarily arising from vertebrae. Primary vertebral body melanomas are rare, surgical decompressions followed by immunotherapy may prolong the survival in this patients.

Utility and pitfalls of high field 3 tesla intraoperative MRI in neurosurgery: A single centre experience of 100 cases.

OBJECTIVE: In India, few centers are using 1.5 Tesla intraoperative MRI systems. We are using a 3 Tesla iMRI system. We share our initial experience of 3T iMRI in neurosurgical procedures with evaluation of its utility and pitfalls. METHODS: A prospective observational study conducted between August 2017 to July 2018 at Yashoda Hospital, Secunderabad. All patients undergoing iMRI guided resection of intracranial SOL were included. RESULTS: First 100 patients with various intracranial SOLs were included. The mean time required in shifting and image acquisition was 85.6 minutes in first 20 cases which was reduced to 37.4 minutes in next the next cases. Primary GTR was achieved in 44% cases, and residues were detected in 56%, secondary GTR was achieved in 37% cases, and surgery was discontinued in 19%. Maximum residues were detected in intraaxial sols and pituitary macroadenomas. No major iMRI associated complications were seen, minor issues involving transportation and minor contact burns were seen in 4 cases, insignificant anesthetic procedure related complications in 19 cases. CONCLUSION: As per our experience iMRI is an excellent tool to guide and improve the extent of safe resection by 37% in brain tumor surgeries. Good image quality, less time for image acquisition was observed advantages of 3T system. iMRI success depends on multidepartment coordinated teamwork and multiple iterations of the process to smoothen the workflow.

Intraoperative Transcranial Embolization following Decompressive Craniectomy for a Dural Arteriovenous Fistula Presenting with Acutely Raised Intracranial Pressure.

We report the clinical details, imaging findings, and management of a 58-year-old female who presented with rapidly deteriorating neurological function and acute raise in intracranial pressure secondary to posterior fossa dural arteriovenous fistula (DAVF). In this report, we present the emergency management of the DAVF with single-stage combined surgical decompressive craniotomy and direct transcranial embolization.

ISNO consensus guidelines for practical adaptation of the WHO 2016 classification of adult diffuse gliomas.

INTRODUCTION: Recent advances in the molecular biology of adult diffuse gliomas have brought about a paradigm shift in their diagnostic criteria, as witnessed in the World Health Organization (WHO) 2016 guidelines for central nervous system tumors. It is now mandatory to perform several molecular tests to reach a definitive integrated diagnosis in most of the cases. This comes with additional cost and higher turnaround time, which is not always affordable in developing countries like India. In addition, the non-uniform distribution of advanced research and diagnostic testing centers adds to the difficulty. METHODS: The Indian Society of Neuro-oncology (ISNO) multidisciplinary expert panel consisting of neuropathologists, neurosurgeons, and radiation/medical oncologists convened to prepare the national consensus guidelines for approach to diagnosis of adult diffuse gliomas. RESULTS: Algorithms for arriving at an integrated diagnosis of adult diffuse gliomas predominantly using immunohistochemistry and with minimum possible additional molecular testing were agreed upon, thus addressing the problems of cost, accessibility, and turnaround time. Mandatory and optional tests were proposed for each case scenario. CONCLUSION: This document represents the consensus of the various neuro-oncology disciplines involved in diagnosis and management of patients with adult diffuse gliomas. The article reflects a practical adaptation of the WHO recommendations to suit a resource constrained setup.

Rete mirabile of posterior inferior cerebellar artery: A rare cause of subarachnoid hemorrhage.

Rete mirabile is a congenital aberrant arterial collateral network resulting from abnormal embryonic activity during native vessel formation. Even though frequently observed in mammals, this entity is rare in humans except when there is hypoplasia, aplasia or narrowing of native vessels. Rete mirabile is reported involving internal carotid and vertebral arteries. Rete mirabile of the posterior inferior cerebellar artery (PICA) is not described in the literature. We report the clinical presentation, imaging findings and management of PICA rete mirabile formation with subarachnoid hemorrhage.

Targeted endovascular treatment of haemorrhagic posterior fossa proliferative angiopathy.

Cerebral proliferative angiopathy (CPA) is a rare vascular abnormality and separate from "classical" brain arteriovenous malformations. Haemorrhage due to proliferative angiopathy is rarely reported. We describe the clinical features, imaging findings and targeted endovascular management for a 12-year-old boy having proliferative angiopathy of the posterior fossa presenting with haemorrhage. Targeted endovascular embolisation in CPA is not previously described in the literature. The optimal treatment options for haemorrhagic CPA are debatable, and we wish to highlight the role of targeted treatment for culprit focal lesion demonstrable on imaging.

Critical neurological structure sparing radiosurgery of vestibular schwannoma: dosimetric comparison of different techniques and dose prescription methods.

AIM: To investigate potential sparing of critical neurological structures (CNSs) during radiosurgery of vestibular schwannoma (VS) employing different techniques and dose prescription methods. MATERIALS AND METHODS: Fused CT and MRI datasets of eight patients with unilateral VS representing a wide range of target volume (0.48 to 12.08 cc; mean = 3.56 cc), shape and proximity to CNSs such as cochlea, trigeminal nerve and brainstem were re-planned employing static conformal field (SCF), dynamic conformal arc (DCA) and intensity modulated radiosurgery (IMRS) techniques. For every patient, five plans were created for a fixed margin dose of 12 Gy prescribed at 80% in three plans (SCF_80%, DCA_80%, and IMRS_80%) and 50% in another two plans (SCF_50% and DCA_50%). All plans were compared using standard dosimetric indices. RESULTS: Primary goal of every plan to cover ≥99% of target volume with 12 Gy was fulfilled for all patients with minimum significant dose to target (D99) ≥11.99 Gy. Best conformity index (CI Paddick = 0.62 ± 0.12) was observed in SCF_80% and DCA_80% plans whereas; sharpest dose gradient index of 3.40 ± 0.40 was resulted from DCA_50%. All five plans resulted similar maximum dose to brainstem (11.04 ± 2.23 to 11.53 ± 1.10 Gy), cochlea (9.02 ± 1.79 to 10.15 ± 1.26 Gy) and trigeminal nerve (11.55 ± 1.38 to 12.19 ± 2.12 Gy). Among 80% prescription plans, IMRS_80% reduces mean and D5 (P < 0.05) to all CNSs. Prescription of dose at 50% isodose sharpened the dose gradient and significantly (P < 0.05) reduced mean dose and D5 to all CNSs at the cost of target conformity (P = 0.01). Mean dose to cochlea and trigeminal nerve were least at 4.53 ± 0.86 and 6.95 ± 2.02 Gy from SCF_50% and highest at 6.65 ± 0.70 and 8.40 ± 2.11 Gy from DCA_80% plans respectively. CONCLUSION: This dosimetric data provides a guideline for choosing optimum treatment option and scope of inter institutional dosimetric comparison for further improvement in radiosurgery of Vestibular Schwannoma (VS).

A fourteen gene GBM prognostic signature identifies association of immune response pathway and mesenchymal subtype with high risk group.

BACKGROUND: Recent research on glioblastoma (GBM) has focused on deducing gene signatures predicting prognosis. The present study evaluated the mRNA expression of selected genes and correlated with outcome to arrive at a prognostic gene signature. METHODS: Patients with GBM (n = 123) were prospectively recruited, treated with a uniform protocol and followed up. Expression of 175 genes in GBM tissue was determined using qRT-PCR. A supervised principal component analysis followed by derivation of gene signature was performed. Independent validation of the signature was done using TCGA data. Gene Ontology and KEGG pathway analysis was carried out among patients from TCGA cohort. RESULTS: A 14 gene signature was identified that predicted outcome in GBM. A weighted gene (WG) score was found to be an independent predictor of survival in multivariate analysis in the present cohort (HR = 2.507; B = 0.919; p<0.001) and in TCGA cohort. Risk stratification by standardized WG score classified patients into low and high risk predicting survival both in our cohort (p = <0.001) and TCGA cohort (p = 0.001). Pathway analysis using the most differentially regulated genes (n = 76) between the low and high risk groups revealed association of activated inflammatory/immune response pathways and mesenchymal subtype in the high risk group. CONCLUSION: We have identified a 14 gene expression signature that can predict survival in GBM patients. A network analysis revealed activation of inflammatory response pathway specifically in high risk group. These findings may have implications in understanding of gliomagenesis, development of targeted therapies and selection of high risk cancer patients for alternate adjuvant therapies.

Necrotizing fasciitis.

Necrotizing fasciitis (NF) is among the most challenging surgical infections faced by a surgeon. The difficulty in managing this entity is due to a combination of difficulty in diagnosis, and also of early as well as late management. For the patient, such a diagnosis means prolonged hospital stay, painful dressings, an extended recovery, and in some unfortunate cases even loss of limb or life. Necrotizing fasciitis is a fairly common condition in surgical practice in the Indian context resulting in a fairly large body of clinical experience. This article reviews literature on MEDLINE with the key words "necrotizing," "fasciitis," and "necrotizing infections" from 1970, as well as from articles cross referenced therein. The authors attempt to draw comparisons to their own experience in managing this condition to give an Indian perspective to the condition.

Glioblastoma-specific protein interaction network identifies PP1A and CSK21 as connecting molecules between cell cycle-associated genes.

Glioblastoma (GBM; grade IV astrocytoma) is a very aggressive form of brain cancer with a poor survival and few qualified predictive markers. This study integrates experimentally validated genes that showed specific upregulation in GBM along with their protein-protein interaction information. A system level analysis was used to construct GBM-specific network. Computation of topological parameters of networks showed scale-free pattern and hierarchical organization. From the large network involving 1,447 proteins, we synthesized subnetworks and annotated them with highly enriched biological processes. A careful dissection of the functional modules, important nodes, and their connections identified two novel intermediary molecules CSK21 and protein phosphatase 1 alpha (PP1A) connecting the two subnetworks CDC2-PTEN-TOP2A-CAV1-P53 and CDC2-CAV1-RB-P53-PTEN, respectively. Real-time quantitative reverse transcription-PCR analysis revealed CSK21 to be moderately upregulated and PP1A to be overexpressed by 20-fold in GBM tumor samples. Immunohistochemical staining revealed nuclear expression of PP1A only in GBM samples. Thus, CSK21 and PP1A, whose functions are intimately associated with cell cycle regulation, might play key role in gliomagenesis.

Identification of potential serum biomarkers of glioblastoma: serum osteopontin levels correlate with poor prognosis.

BACKGROUND: The aim of this study is to identify serum biomarkers with classification and prognosis utility for astrocytoma, in particular glioblastoma (GBM). METHODS: Our previous glioma microarray database was mined to identify genes that encode secreted or membrane-localized proteins. Subsequent analysis was done using significant analysis of microarrays, followed by reverse transcription-quantitative PCR (RT-qPCR) and immunohistochemical validation in tumor tissues, ELISA and Western blot validation in sera, and correlation with survival of GBM patients. RESULTS: Significant analysis of microarrays identified 31 upregulated and 3 downregulated genes specifically in GBMs. RT-qPCR validation on an independent set of samples confirmed the GBM-specific differential expression of several genes, including three upregulated (CALU, CXCL9, and TIMP1) and two downregulated (GPX3 and TIMP3) novel genes. With respect to osteopontin (OPN), we show the GBM-specific upregulation by RT-qPCR and immunohistochemical staining of tumor tissues. Elevated serum OPN levels in GBM patients were also shown by ELISA and Western blot. GBM patients with high serum OPN levels had poorer survival than those with low serum OPN levels (median survival 9 versus 22 months respectively; P = 0.0001). Further, we also show high serum TIMP1 levels in GBM patients compared with grade II/III patients by ELISA and downregulation of serum GPX3 and TIMP3 proteins in GBMs compared with normal control by Western blot analysis. CONCLUSIONS: Several novel potential serum biomarkers of GBM are identified and validated. High serum OPN level is found as a poor prognostic indicator in GBMs. IMPACT: Identified serum biomarkers may have potential utility in astrocytoma classification and GBM prognosis.

Grade-specific expression of insulin-like growth factor-binding proteins-2, -3, and -5 in astrocytomas: IGFBP-3 emerges as a strong predictor of survival in patients with newly diagnosed glioblastoma.

BACKGROUND: Insulin-like growth factor (IGF)-binding protein (IGFBP) isoforms have been implicated in the pathogenesis of human neoplasms including glioma. In view of this, we evaluated the expression of IGFBP isoforms (IGFBP-2, -3, and -5) during malignant progression of astrocytoma and their prognostic significance in glioblastoma. METHODS: The expression of IGFBP isoforms was analyzed in diffusely infiltrating astrocytomas by real-time quantitative PCR (n = 203) and immunohistochemistry (n = 256). Statistical methods were used to assess their grade-specific expression pattern and mRNA-protein intercorrelation. Survival analyses were done on a uniformly treated, prospective cohort of adult patients with newly diagnosed glioblastoma (n = 136) by using Cox regression models. RESULTS: The mean transcript levels of IGFBP-2 and -3 were significantly higher in glioblastomas (GBM) relative to anaplastic astrocytoma (AA), diffuse astrocytoma (DA), and controls whereas IGFBP-5 mRNA was higher in GBM relative to AA and controls (P < 0.05). By immunohistochemistry, the mean labeling index of all isoforms was significantly higher in GBM compared with AA, DA, and control (P < 0.05). A strong positive correlation was observed between their respective mRNA and protein expressions (P < 0.01). Multivariate analysis revealed IGFBP-3 expression (hazard ratio, 1.021; P = 0.030) and patient age (hazard ratio, 1.027; P = 0.007) to be associated with shorter survival in glioblastoma. CONCLUSIONS: This study shows the associations of IGFBP-2, -3, and -5 expression with increasing grades of malignancy in astrocytomas. IGFBP-3 is identified as a novel prognostic glioblastoma biomarker. The strong correlation between their mRNA and protein expression patterns suggests their role in the pathogenesis of these tumors. IMPACT: IGFBP isoforms have emerged as biomarkers with diagnostic and prognostic utility in astrocytomas.

Recurrence in medulloblastoma - influence of clinical, histological and immunohistochemical factors.

INTRODUCTION: The therapy for medulloblastomas has gone through several changes over the years. Research has shown that patients with medulloblastoma cannot be satisfactorily stratified into risk groups based on clinical and therapeutic factors alone. AIM: To study the clinical, histological features and expression of immunohistochemical markers in medulloblastoma, and to correlate these features with recurrence rates. MATERIALS AND METHODS: Sixty-three cases of medulloblastomas operated at our institute from 1996-2003 were selected and retrospectively analyzed for therapy received, histological features and immunohistochemical expression of GFAP, synaptophysin, erb B2, p53, Bcl-2 and Trk-C along with assessment of MIB-1 labeling index(LI). RESULTS: The mean age of the 63 cases at presentation was 11.6 yrs. Near/Gross- total resection was achieved in 74.6% (47/63) of the cases. CONCLUSION: We propose a clinical-histological-immunohistochemical' model for medulloblastoma where extent of resection, administration of chemotherapy, presence of gross anaplasia and c-erb B2 overexpression status are the most important predictors of recurrence rates.

Outcome of ventriculoperitoneal shunt placement in Grade IV tubercular meningitis with hydrocephalus: a retrospective analysis in 95 patients. Clinical article.

OBJECT: Hydrocephalus is the most common complication of tubercular meningitis (TBM). Relieving hydrocephalus by ventriculoperitoneal (VP) shunt placement has been considered beneficial in patients in Palur Grade II or III. The role of VP shunt placement in those of Grade IV is controversial and the general tendency is to avoid its use. Some authors have suggested that patients in Grade IV should receive a shunt only if their condition improves with a trial placement of an external ventricular drain (EVD). In the present study, the authors assessed the outcome of VP shunt placement in patients in Grade IV TBM with hydrocephalus to examine the factors predicting outcome and to determine whether a trial with an EVD is absolutely necessary prior to shunt placement. METHODS: Ninety-five consecutive cases of TBM with hydrocephalus in which the patients underwent VP shunt placement were retrospectively analyzed, and direct VP shunts were placed whenever possible. An EVD was placed first only in the presence of deranged blood parameters. Outcomes were assessed both in the short and long term. RESULTS: The mean patient age was 17.5 years (range 1-55 years). Fifty-two patients underwent direct VP shunt placement, and the remaining 43 received EVDs first. Overall, 33 and 45% of patients had favorable short- and long-term outcomes, respectively. Age older than 3 years and duration of altered sensorium < or = 3 days were predictive of a favorable short-term outcome. Glasgow Coma Scale score at presentation was predictive of long-term outcome. Of the patients who did not improve with placement of an EVD prior to VP shunt insertion, 24 and 18% had favorable short- and long-term outcomes, respectively; this was not significantly different from the outcome in the patients who underwent direct VP shunt placement. CONCLUSIONS: Direct VP shunt placement is an effective option in patients with Grade IV TBM with hydrocephalus. Age and duration of altered sensorium are predictive of short-term outcome, while Glasgow Coma Scale score at presentation predicts long-term outcome. Ventriculoperitoneal shunts should be considered even in patients who do not improve with an EVD.

Fatal intratumoral hemorrhage in posterior fossa tumors following ventriculoperitoneal shunt.

We report on two patients with rare major intratumoral hemorrhage following ventriculoperitoneal shunt in posterior fossa tumors. A 28-year-old woman with a midline posterior fossa lesion, whose imaging features suggested a fourth ventricular ependymoma with obstructive hydrocephalus, was subjected to a right ventriculoperitoneal shunt. Her consciousness deteriorated, and she experienced massive intratumoral hemorrhage and later died. An eight-year-old girl presented with raised intracranial pressure and ataxia caused by vermian astrocytoma with obstructive hydrocephalus. She also developed a massive tumor bleed following a ventriculoperitoneal shunt and was subjected to emergency decompression of the tumor with the bleeding. She remained vegetative at discharge and died 18 months later. Intratumoral hemorrhage is a rare but important cause of morbidity and mortality in patients with posterior fossa tumors who undergo ventriculoperitoneal shunt.