Shashwat Tripathi

Glioblastoma (GBM) is most common and aggressive primary brain tumor in adults, for which standard of care hasn’t changed in twenty years. GBM tumor associated macrophages (TAMCs), consisting of infiltrating myeloid cells from the periphery and resident microglia cells, are pro-tumorigenic, promoting tumor growth. Fructose is one of the most abundant metabolites in the GBM tumor microenvironment (TME), as well as in the healthy central nervous system (CNS). In the CNS and GBM, microglia are the predominant expressors of the fructose transporter GLUT5. Mice lacking the GLUT5 transporter (GLUT5-KO) survive significantly longer after orthotopic implantation of two glioma cell lines than wildtype mice, which is not due to dietary fructose or peripherally derived TAMCs. Investigation of the TME showed that GLUT5-KO mice have more highly activated and inflammatory innate and adaptive immune compartments. Microglia cultured in fructose have a decreased phagocytic ability and exhibit decreased inflammatory capacity due to the polyol pathway promoting redox homeostasis.

Median survival of patients with glioblastoma (GBM) treated with standard of care which consists of maximal safe resection of the contrast-enhancing portion of the tumor followed by radiation therapy with concomitant adjuvant temozolomide (TMZ) remains 15 months. The tumor microenvironment (TME) is known to contain immune suppressive myeloid cells with minimal effector T cell infiltration. Stimulator of interferon genes (STING) is an important activator of immune response and results in production of Type 1 interferon and antigen presentation by myeloid cells. This review will discuss important developments in STING agonists, potential biomarkers for STING response, and new combinatorial therapeutic approaches in gliomas.

OBJECTIVE: Epilepsy is common among patients with supratentorial brain tumors; approximately 40%–70% of patients with glioma develop brain tumor–related epilepsy (BTRE). Intraoperative localization of the epileptogenic zone during surgical tumor resection (real-time data) may improve intervention techniques in patients with lesional epilepsy, including BTRE. Accurate localization of the epileptogenic signals requires electrodes with high-density spatial organization that must be placed on the cortical surface during surgery. The authors investigated a 360° high-density ring-shaped cortical electrode assembly device, called the “circular grid,” that allows for simultaneous tumor resection and real-time electrophysiology data recording from the brain surface.METHODS: The authors collected data from 99 patients who underwent awake craniotomy from January 2008 to December 2018 (29 patients with the circular grid and 70 patients with strip electrodes), of whom 50 patients were matched-pair analyzed (25 patients with the circular grid and 25 patients with strip electrodes). Multiple variables were then retrospectively assessed to determine if utilization of this device provides more accurate real-time data and improves patient outcomes.RESULTS: Matched-pair analysis showed higher extent of resection (p = 0.03) and a shorter transient motor recovery period during the hospitalization course (by approximately 6.6 days, p ≤ 0.05) in the circular grid patients. Postoperative versus preoperative Karnofsky Performance Scale (KPS) score difference/drop was greater for the strip electrode patients (p = 0.007). No significant difference in postoperative seizures between the 2 groups was present (p = 0.80).CONCLUSIONS: The circular grid is a safe, feasible tool that grants direct access to the cortical surgical surface for tissue resection while simultaneously monitoring electrical activity. Application of the circular grid to different brain pathologies may improve intraoperative epileptogenic detection accuracy and functional outcomes, while decreasing postoperative complications.

Ancient Egyptian civilization is one of the oldest cultures in human history. Ancient Egyptians are well-known for pioneering the fields of art, medicine, and the documentation of discoveries as mythological tales. The Egyptians mastered the integration of anatomy and mythology into artistic symbols and figures. The mythology of Isis, Osiris, and Horus is arguably one of the most recognized mythologies in ancient Egypt. The Eye of Horus was used as a sign of prosperity and protection, derived from the myth of Isis and Osiris. This symbol has an astonishing connection between neuroanatomical structure and function. Artistically, the Eye is comprised of six different parts. From the mythological standpoint, each part of the Eye is considered to be an individual symbol. Additionally, parts of the Eye represent terms in the series 1/2, 1/4, 1/8, 1/16, and 1/32; when this image is superimposed upon a sagittal image of the human brain, it appears that each part corresponds to the anatomic location of a particular human sensorium. In this manuscript, we highlight the possible scientific speculation of the ingenuity of ancient Egyptians’ remarkable insight into human anatomy and physiology.

The ancient Egyptian and Peruvian Civilizations are two of the earliest cultures in human history. Through medical and architectural similarities, we wish to show a possible connection between these two cultures. A literature search was conducted by searching the database of Medline, National Geographic magazine, history books, and Google Scholar using the search terms: neurosurgery, pyramids, pyramidal architectures, ancient Egypt, ancient Peru, the connection between ancient Egypt and Peru. Both the ancient Egyptian and Peruvian Civilizations are well-known for their pioneering work in medicine and architecture; their accomplishments in these areas have been well-documented in the walls of uncovered tombs and discovered papyrus. Both these cultures also firmly believed in an afterlife and built pyramids to serve as tombs and homes for royalty in the afterlife. The sloping sides of the pyramids were inclined to signify the emergence of the physical body from Earth towards the Sun. Both civilizations independently pioneered the art of neurosurgery with different techniques and approaches. In this paper, we discuss the potential links between both civilizations. We recognize and appreciate the brilliance of these ancient cultures in mastering the medicinal and architectural sciences.

Zoledronic acid is an intravenous bisphosphonate used to increase bone mineral density and reduce the risk of fractures. Its safety profile compares well with pamidronate in pediatric patients. We describe an acute, severe, life-threatening, inflammatory reaction in a child. A 7-year-old boy with complex medical problems and chronic ventilator requirements was admitted to the pediatric intensive care unit (due to ventilator needs) for zoledronic acid infusion and subsequent monitoring. His history was significant for osteoporosis secondary to immobilization with multiple fractures since 2 years of age, hypoxic-ischemic encephalopathy, quadriplegic cerebral palsy, seizure disorder, ventilator dependence, and pulmonary hypertension. He had previously been treated with four cycles of pamidronate without adverse events. He received 0.013 mg/kg of zoledronic acid infused over 30 minutes. Beginning 3 hours after completion of the infusion, he developed progressive tachycardia, fever, hypotension requiring vasopressor infusion, and increasing oxygen requirements. Laboratory studies revealed leukopenia, thrombocytopenia, elevated C-reactive protein, abnormal coagulation profile, metabolic acidosis, and negative cultures. The following day, he developed moderate acute respiratory distress syndrome and pulmonary hemorrhage requiring higher ventilatory settings, and subsequently diarrhea and abdominal distension. Initial clinical resolution was noted from the third day onward, and he was discharged on the sixth day after zoledronate administration. Our pediatric patient demonstrated an acute, severe, life-threatening reaction to zoledronic acid requiring intensive cardiorespiratory support without an underlying pre-existing inflammatory disorder. Our case highlights the importance of careful monitoring of children following zoledronic acid therapy. We recommend inpatient observation after an initial infusion of zoledronic acid in medically complex children. Children and their parents should be thoroughly counseled on the potential risks of bisphosphonate treatment, which can sometimes be severe and life threatening.