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.

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.

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.

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.

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.

Does Tc-99m ECD ictal brain SPECT have incremental value in localization of epileptogenic zone and predicting postoperative seizure freedom in cases with discordant video electroencephalogram and MRI findings?

OBJECTIVE: Localization of epileptogenic focus in drug-refractory epilepsy using Tc-99m ethylene cystine dimer (ECD) brain single photon emission computed tomography (SPECT) is less studied in patients with discordant findings on video electroencephalogram (VEEG) and MRI. The study was done to evaluate brain SPECT for epileptogenic focus localization and postoperative seizure freedom. METHODS: Epilepsy patients with discordant VEEG and MRI findings underwent brain SPECT at ictal and interictal phases. Various groups unilateral/bilateral mesial temporal sclerosis (MTS), solitary and multifocal lesional, nonlesional epilepsy were studied for localization of epileptogenic focus and postoperative seizure freedom (>2 years) using Engels classification. Reasons for nonoperability was evaluated in nonoperated group. RESULTS: SPECT could localize epileptogenic focus in 49/67 (73.13%) and guided surgery in 19/33 (57.57%) patients in operated group. SPECT was useful in 12 (46.12%) of unilateral (2)/bilateral (10) MTS. Postoperative seizure freedom of Engels Class I and II in 22 (66.67%), III in six (18.2%) and IV in one patient based on SPECT findings (P = 0.0086). Overall sensitivity and specificity were 79.3% and 85.7%, respectively. SPECT could localize epileptogenic focus in 23/34 (67.64%) patients in nonoperated group; 10 (29.41%) patients refused for surgery and no epileptogenic focus was localized in the rest of 14 (41.2%). CONCLUSION: Ictal SPECT showed incremental value and was found necessary for epileptogenic focus localization and subsequent surgery in unilateral/bilateral MTS in this study. Seizure freedom in patients undergoing epilepsy surgery based on ictal SPECT assistance was comparable to the surgical group not requiring ictal SPECT.

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.

Sitting Position for Posterior Fossa Tumor in Infants: A Technical Report.

Surgery for posterior fossa tumors in sitting position is performed in very few neurosurgical centers all over the world. It carries the potential risk of air embolism with consequent related morbidity. However, posterior fossa surgery in the sitting position is still performed in neurosurgical centers with considerable expertise including neurosurgeons and neuroanesthesiologists. In older children and young adults, the sitting position is given with the appropriate modifications in the operating surgical table and the head fixation system. In infants, due to the small size of the baby and delicate physiology, the sitting position using standard protocol is challenging. A custom designed chair and its suitability for sitting position in infants is described. The chair assembly is secured to the operating surgical table. It is meant to align the infant in sitting position in an appropriate manner. The relevant surgical details including the advantages and limitations are discussed.

A Treatise on Pediatric Meningiomas: Single-center Retrospective Cohort Experience and Review of Literature.

BACKGROUND: Pediatric meningiomas are infrequently encountered in clinical practice. In comparison to adults, they have a distinct pathophysiology and clinical presentation. They are benign but locally aggressive tumors. Radical excision often culminates in good outcome. AIM: The aim of this study was to study the demographic profile, clinico-radiological features, pathophysiology, and surgical outcome of childhood meningiomas. MATERIALS AND METHODS: The case records of patients <18 years of age operated for meningiomas in our institute from 1985 to 2015 were retrieved. The demographic profile, clinical and radiological features, surgical approach, extension of resection, and surgical outcome were recorded and subsequently analyzed. RESULTS: Among 37 patients, 20 were males and 17 were females. The mean age was 13 years. Predisposing etiologies such as neurofibromatosis and radiation exposure were identified in 20% of the study population. There were 31 intracranial and 6 spinal meningiomas. Headache associated with vomiting was the most common presenting complaint. Majority were supratentorial tumors. A safe maximal excision was attempted in each case. Recurrence was noted in five patients. Average follow-up was approximately 24 months. Two patients succumbed to the illness. Approximately, 30% of patients were rendered morbid. CONCLUSION: Although rare, pediatric meningiomas are biologically different from their adult counterparts. They have a male predominance, common in intraventricular region and cystic in nature. Radical excision is associated with good prognosis. Although benign, they are aggressive in nature and have a tendency to recur. The response to adjuvant therapy is modest. Further molecular research and genetic studies are necessary to understand the biology of pediatric meningiomas, which will help in the identification of targeted molecular therapy.

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.

Attenuation of Tumor Suppressive Function of FBXO16 Ubiquitin Ligase Activates Wnt Signaling In Glioblastoma.

Glioblastoma (GBM) is one of the most aggressive and lethal types of brain tumor. Despite the advancements in conventional or targeted therapies, median survival of GBM patients is less than 12 months. Amongst various signaling pathways aberrantly activated in glioma, active Wnt/ß-catenin signaling pathway is one of the crucial oncogenic players. ß-catenin, an important mediator of Wnt signaling pathway, gets phosphorylated by GSK3ß complex. Phosphorylated ß-catenin is specifically recognized by ß-Trcp1, a F-box/WD40-repeat protein and with the help of Skp1 it plays a central role in recruiting phosphorylated ß-catenin for degradation. In GBM, expression of ß-TrCP1 and its affinity for ß catenin is reported to be very low. Hence, we investigated whether any other members of the E3 ubiquitin ligase family could be involved in degradation of nuclear ß-catenin. We here report that FBXO16, a component of SCF E3 ubiquitin ligase complex, is an interacting protein partner for ß-catenin and mediates its degradation. Next, we show that FBXO16 functions as a tumor suppressor in GBM. Under normal growth conditions, FBXO16 proteasomally degrades ß-catenin in a GSK-3ß independent manner. Specifically, the C-terminal region of FBXO16 targets the nuclear ß-catenin for degradation and inhibits TCF4/LEF1 dependent Wnt signaling pathway. The nuclear fraction of ß-catenin undergoes K-48 linked poly-ubiquitination in presence of FBXO16. In summary, we show that due to low expression of FBXO16, the ß-catenin is not targeted in glioma cells leading to its nuclear accumulation resulting in active Wnt signaling. Activated Wnt signaling potentiates the glioma cells toward a highly proliferative and malignant state.

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.

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.