Surgery for Central Nervous System Tuberculosis in Children.

Tuberculosis (TB) is the second most common cause of death due to a single infectious agent worldwide after COVID-19. Central nervous system tuberculosis is widely prevalent in the world, especially in the developing countries and continues to be a socioeconomic problem. It is highly devastating form of tuberculosis leading to unacceptable levels of morbidity and mortality despite appropriate antitubercular therapy. The clinical symptoms are varied and nonspecific. They can be easily overlooked. Tuberculous meningitis is the most common presentation and its sequelae viz. vasculitis, infarction and hydrocephalus can be devastating. The ensuing cognitive, intellectual, and endocrinological outcome can be a significant source of morbidity and mortality, especially in resource constrained countries. Early diagnosis and treatment of tuberculous meningitis and institution of treatment is helpful in limiting the course of disease process. The diagnosis of CNS tuberculosis remains a formidable diagnostic challenge. The microbiological methods alone cannot be relied upon. CSF diversion procedures need to be performed at the appropriate time in order to achieve good outcomes. Tuberculous pachymeningitis and arachnoiditis are morbid sequelae of tuberculous meningitis. Tuberculomas present as mass lesions in the craniospinal axis. Tuberculous abscess can mimic pyogenic abscess and requires high index of suspicion. Calvarial tuberculosis is seen in children and responds well to antituberculous chemotherapy. Tuberculosis of the spinal cord is seen similar to intracranial tuberculosis in pathogenesis but with its own unique clinical manifestations and management. Multidrug-resistant tuberculosis is a formidable problem, and alternate chemotherapy should be promptly instituted. The pathogenesis, clinical features, diagnosis, and management of central nervous system tuberculosis in children are summarized. Heightened clinical suspicion is paramount to ensure prompt investigation. Early diagnosis and treatment are essential to a gratifying outcome and prevent complications.

NSG-70, a new glioblastoma cell line with mixed proneural-mesenchymal features, associates NOTCH1-WNT5A signaling with stem cell maintenance and angiogenesis.

BACKGROUND: Glioblastoma initiation and progression is believed to be driven by Glioma stem cells (GSCs). Activation of NOTCH1 and WNT, and more recently, non-canonical WNT5A signaling, has been demonstrated to regulate self-renewal and differentiation of the GSCs crucially. High expression levels of NOTCH1 and WNT in GBM tumors contribute to the sustenance of GSCs and mediate characteristic phenotypic plasticity, which is reflected by the different subtypes and tremendous intra-tumor heterogeneity. However, the coregulation of NOTCH1 and WNT5A is not well understood. Here, we studied the role of these molecules in regulating the characteristics of different GSC subtypes. METHODS: We established a novel GSC-enriched cell model, referred to as NSG-70, from a patient with recurrent GBM. NSG-70 cells harbor a unique cytogenetic feature, viz. isochromosome 9q. At the same time, its expression profiles indicate that it is a mixed lineage comprising proneural and mesenchymal subtypes. We examined the relevance of NOTCH1 and WNT5A signaling and their coordinated action in GBM using these cells and other patient-derived models representing different GSC subtypes. RESULTS: Our data revealed that the downregulation of NOTCH1 resulted in the suppression of stem cell and mesenchymal markers and significantly reduced the levels of WNT5A. NOTCH1 knockdown also led to a notable reduction in the vasculogenic mimicry of GSCs. Interestingly, knockdown of WNT5A exhibited similar effects and drove quiescent GSC towards proliferation. In a complementary manner, ectopic expression of WNT5A or rhWNT5A treatment rescued the effects of NOTCH1 knockdown. CONCLUSION: The resistance of GSCs towards conventional therapies in part due to subtype interconversion demands therapies targeting specific GSC subtype. Our study suggests the need for a combinatorial approach that could effectively target the NOTCH1-WNT5A signaling axis toward eliminating GSCs.

Utility of CISS imaging in the management of tethered cord syndrome.

OBJECTIVE: To compare the utility of constructive interference in steady-state (CISS) sequence over T2-weighted (T2W) sequence in the accurate delineation of the tethering element on magnetic resonance (MR) imaging in patients of tethered cord syndrome (TCS) and correlation with intraoperative findings. METHODS: MR findings of fifty-six consecutive patients with operative findings of TCS were studied. The intraoperative findings of all patients were studied and compared with the preoperative imaging findings on T2W imaging and CISS images. RESULTS: CISS images provided more information than T2W imaging. The overall sensitivity of CISS in MR evaluation of patients with TCS was higher (99.17%) as compared with the T2W sequence (71.48%) especially in the detection of precise position/extent of tethered cord, assessment of filum terminale thickening, detection of a fibrous spur in cases of split cord malformation, detection of dorsal dermal sinus, and evaluation of its precise extent and ramifications. The area under the ROC curve was higher with CISS (0.99) than with T2W sequence (0.85) which reflects its good predictive value as a screening test. This information was useful to the operating surgeon. CONCLUSION: CISS sequence for imaging TCS can help enhance the overall surgical outcome of the patients ensuring completeness of the surgery. CISS should be routinely performed in the work-up of patients with tethered cord syndrome.

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.

Tuberculosis of the central nervous system in children.

BACKGROUND: Central nervous system tuberculosis (CNS TB) in children is still a socioeconomic problem in developing countries. It has varied manifestations, symptoms are nonspecific, diagnosis can be challenging, and treatment may be difficult. It is often missed or overlooked. Among the various pathological entities, tuberculous meningitis is the most common and devastating manifestation. The resultant vasculitis, infarction, and hydrocephalus can be life-threatening. It can have grave cognitive, intellectual, and endocrine sequelae if not treated in time resulting in handicap, especially in resource constraint countries. Early diagnosis and treatment of tuberculous meningitis is the single most important factor determining outcome. Tuberculous hydrocephalus needs to be recognized early, and cerebrospinal fluid diversion procedure needs to be performed in adequate time to prevent morbidity or mortality in some cases. Tuberculous pachymeningitis and arachnoiditis are rare in children. Tuberculous abscess can mimic pyogenic abscess and requires high index of suspicion. Calvarial tuberculosis is seen in children and responds well to antituberculous chemotherapy. Drug-resistant tuberculosis is a formidable problem, and alternate chemotherapy should be promptly instituted. AIM: The pathogenesis, clinical features, diagnosis, and management of central nervous system tuberculosis in children are summarized. CONCLUSION: Heightened clinical suspicion, early diagnosis, appropriate antituberculous treatment, and surgery in relevant situation are essential for a gratifying outcome and preventing complications.

Subdural empyema in children.

BACKGROUND: Subdural empyema denotes the collection of purulent material in the subdural spaceand is commonly seen in infants and older children. In infants, the most common cause is bacterialmeningitis. In older children, sinusitis and otitis media are usually the source for subdural empyema. Theclinical symptomatology is varied and has a wide range including prolonged or recurrent fever, seizures,meningeal irritation, and raised intracranial pressure. It can mimic as well as complicate meningitis and aheightened clinical awareness is therefore paramount. AIMS AND OBJECTIVES: The clinical profile, etiopathogenesis, imaging features and management of subdural empyema in children is discussed and the relevant literature is reviewed. CONCLUSION: Subdural empyema is a neurosurgical emergency and rapid recognition and treatment canavoid life-threatening complications. In most cases, surgical decompression through burr hole or craniotomyis warranted. Near complete evacuation of the purulent material and appropriate long-term intravenous antibiotics are necessary for a gratifying outcome.

Management of brain abscesses: where are we now?

INTRODUCTION: Brain abscesses affect all age groups and are not peculiar to a particular country, race, or geographical location. It is a disease that, in the past, carried a high morbidity and mortality. With improvements in medical technology and expertise, outcomes have improved tremendously. The causative organisms vary vastly and have evolved with time. Treatment of brain abscesses is primarily with antimicrobial therapy but surgery plays a vital role in achieving better outcomes. CONTENT: In this article, we review the literature to find out how the epidemiology of this disease has changed through the years and re-visit the basic pathological process of abscess evolution and highlight the new research in the biochemical pathways that initiate and regulate this process. We also highlight how magnetic resonance imaging and its various modalities have improved diagnostic accuracy. Finally, we discuss the pros and cons of traditional open surgery versus newer minimally invasive methods.

Brain abscess: Heuristics, principles, pathobiology, practice.

Brain abscess is an uncommon but a compelling reality in neurosurgical practice. Its focal, local, and systemic manifestations conceal its infective and obsessive nature. There are many a lesson that a brain abscess, as a bio-phenomenon, offers to the medical fraternity in general and the neurosurgeons, in particular. From Skt. puyati = to stink, comes the word "pus," meaning something foul, putrid, or rotten. From ab = away, and cedre = to go, comes the term "abscess" which is but nature's ingenious way of creating a fluid-filled cavity that will eventually rupture to an exterior to get rid of the non-self contents and proceed to healing. A brain abscess is special in the sense that it is, in general, more solid than fluid for reasons the human body and brain know best.

Cavernoma of the septum pellucidum in the region of foramen of Monro.

A rare case of cavernoma in the region of the septum pellucidum is reported. A 35-year-old female patient presented with chronic headaches. Her neurological exam was normal. Her magnetic resonance (MR) imaging showed a lesion within the inferior aspect of the septum pellucidum extending into the anterior third ventricular region, blocking the foramen of Monro, resulting in moderate supratentorial asymmetrical hydrocephalus. A central neurocytoma or subependymoma was suspected on imaging. Complete excision of the septum pellucidum cavernoma was performed using microneurosurgical techniques through an interhemispheric transcallosal route. The patient had an excellent outcome and is cured. Although rare, septum pellucidum cavernomas should be considered in the differential diagnosis of anterior third ventricular lesions in the region of foramen of Monro. The unusual location, atypical radiological features, differential diagnosis as well as surgical nuances in the management of a cavernoma in the septum pellucidum and anterior third ventricular region are discussed in the light of current literature.

Wnt3a mediated activation of Wnt/ß-catenin signaling promotes tumor progression in glioblastoma.

Presence of a distinct population of cells that drives tumor progression supports the hierarchical model of tumor development in Glioblastoma (GBM) and substantiates the cancer stem cell hypothesis. Amongst the various developmental signaling pathways that are aberrantly activated, we here show that activated Wnt/ß-catenin signaling pathway plays a critical role in malignant transformation and tumor progression in gliomas. We demonstrate that Wnt ligands - Wnt1 and Wnt3a are expressed in a graded manner in these tumors as well as over-expressed in glioma stem cell-lines. A selective inhibition of Wnt signaling pathway by selective knock-down of its ligands Wnt1 and Wnt3a in glioma-derived stem-like cells led to decreased cell proliferation, cell migration and chemo-resistance. Furthermore, Wnt silencing in glioma cells reduced the capacity to form intra-cranial tumors in vivo. Taken together, our study indicates Wnt/ß-catenin signaling pathway as an essential driver of glioma tumorigenesis, recognizing role of Wnt3a as an oncogene and thereby offering novel therapeutic strategies for management of these tumors.

Anchoring the Temporalis Muscle with an Intact Fascial Layer Along the Superior Temporal Line in Pterional Craniotomy: A Technical Note.

BACKGROUND: Manipulation of the temporalis muscle during pterional and frontotemporal approaches poses major cosmetic and functional issues postoperatively. The temporalis muscle has usually been secured in its normal position using implants or by leaving a thin rim of muscle and fascia attached along the superior temporal line. In the present report, we have described a pure tissue-based method of anchoring the intact temporalis muscle precisely along the superior temporal line. METHODS: A total of 30 consecutive cases of pterional or frontotemporal craniotomy were performed by single surgeon (SKR). A subfascial dissection technique was used to expose the transition zone of the frontal pericranium with the temporalis fascia. These were then separated by sharp dissection along the superior temporal line at which the muscle is attached. The temporalis muscle and fascia were repositioned during closure, precisely at their original anatomical location by passing multiple anchoring sutures along the free edge of the muscle and fascia lying along the superior temporal line. RESULTS: Temporalis muscle reattachment was achieved in all 30 cases with good cosmesis and functional outcome without temporalis muscle-related complications at 6 months of follow-up. CONCLUSIONS: The approximation of sutures running through the free edge of the temporalis muscle with intact fascia along the superior temporal line from anteriorly to posteriorly restored the muscle and fascial layer to its original position. Avoidance of the formation of any potential dead space during surgical exposure will prevent periorbital edema and/or subgaleal collection postoperatively. The described inexpensive technique avoids implant-related complications, with good functional and aesthetic outcomes. A comparative study is needed to establish the superiority of this procedure over other techniques.

Epigenetic regulation of DNA methyltransferases: DNMT1 and DNMT3B in gliomas.

The role of epigenetics and significance of aberrant gene regulation in etiology of cancer is a well-established phenomenon. The hallmark of cancer epigenetics is aberrant DNA methylation consisting of global hypomethylation and regional hypermethylation of tumor suppressor genes (TSGs) by DNA methyltransferases (DNMTs). In mammals, DNA methylation is catalyzed by DNMTs encoded by DNMT1, DNMT3A, and DNMT3B. Interestingly, little is known about variation in the methylation status of epigenetic regulators themselves in gliomas. Here, we report significant overexpression of DNMT1 and DNMT3B. A study of the methylation status and histone modifications at the promoter region of DNA methyltransferase I (DNMT1) gene revealed an unmethylated DNA promoter, similar to that detected in normal brain tissues. However, a differential histone code with distinct euchromatin marks--AcH3, AcH4, and H3k4me2--was specifically detected in tumors, unlike in normal brain tissues, which were found predominantly enriched with heterochromatin marks such as H3K9me2 and H3K27me3. In contrast, a differential methylation pattern of DNMT3B gene promoter occurred in glioma tumors, wherein it was found hypomethylated. Transcriptional silencing by CpG island methylation is a prevalent mechanism for inactivation of TSGs. Inhibiting DNMTs by 5-azacytidine (DNMT inhibitor) treatment led to significant inhibition of expression of DNMT1 and DNMT3B and enhanced expression of TSGs such as PTEN and p21 analyzed in this study. Our studies have identified effects of increased presence of DNMTs on inhibition of tumor suppressors that are epigenetically silenced in gliomas, thereby leading to aberrant regulation of cell cycle progression and failure to maintain genomic stability.

Open Neural Tube Defects in COVID-19 Pandemic: An Analysis of 26 Neonatal Patients in a Tertiary Care Center.

Coronavirus disease-2019 (COVID-19) pandemic has severely affected and disrupted medical practice all over the world since December 2019 till date. This has affected the pediatric surgical practice in general and neurosurgical practice in particular. An analysis of 26 neonatal patients with open neural tube defects who underwent surgery in the neurosurgery department at the King Edward VII Memorial Hospital (KEM), Mumbai during the period of March 2020 till December 2020 is presented. The cumulative experience and challenges encountered in the comprehensive management of these cohort of patients in the difficult period of the pandemic is discussed in accordance with relevant literature on the subject.

Split Cord Malformation Type 1 (Bony Spur) Excision Using Microrongeur.

Split cord malformation is well documented and reported in various case series and reports in the literature. The excision of bony spur in type 1 split cord malformation is challenging due to the intricate pathologic anatomy. The standard method advocated is to excise the bony spur with the help of a high-speed microdrill and a forward cutting punch. We describe a novel method of using fine-tipped slender microrongeur, which can negotiate the narrow confines harboring the bony spur and protect the adjacent hemicords. The surgical nuances are detailed and discussed.