The creation of a global neurotrauma registry.

The authors propose the generation of a multi-institutional TBI registry. Barriers to registry implementation include: (1) difficulties in acquiring ethical approval; (2) incomplete clinical data available; (3) lack of information and insufficient technology (IT) support; (4) limited available resources; (5) time constraints involving understaffing yet managing high patient volumes; (6) time constraints associated with entering patient data into the registry tool. The authors detail the current state of affairs on neurotrauma registries worldwide and propose the creation of a multi-institutional, global neurotrauma registries. This private-public partnership will enable appropriate balance among stakeholders while offering care to the largest number of citizens. This initiative will require coordinated efforts involving vetted members of organized neurosurgery. Support from these entities, such as fellowship program creation, provided funding through travel vouchers to LMICs, secured housing and transportation costs in LMI nations, facilitated meetings with global local stakeholders, and promotion of key developments via social media, will accelerate the creation of this global neurotrauma registry. We propose the creation of a global TBI registry, in partnership with large, academic medical centers. Several proposed limitations of registry implementation can be addressed with support from local stakeholders, including government officials and administrative members at key institutions. Several American institutions have well-established global health programs to support this initiative. Further, at Harvard Medical School, the program in Global Surgery and Social Change offers the Paul Farmer Global Surgery Fellowship that trains leaders in policy development and implementation. The fellowship consists of 2 separate tracks: a 2-year research fellow (PGY-5-PGY-6) and 1-year research associate (MD and MBBS, etc.). Funding could be allocated towards creating a year-long fellowship dedicated towards implementing a neurotrauma registry, with this selected scholar granted the resource and connections to network with government officials and healthcare groups in every nation within that jurisdiction. A scholar would be assigned a region of the world with the goal to generate a registry that would later be combined with those generated by peer scholars. In addition, we propose the creation of a fund, controlled by donors, as a funding model.

Vein of galen malformations: for patients and caregivers.

Vein of Galen malformations (VOGMs), also known as Vein of Galen Aneurysmal Malformations (VGAMs), are rare and complex cerebrovascular anomalies that pose significant diagnostic and therapeutic challenges. These malformations result from abnormal arteriovenous shunts during embryonic development, leading to a range of severe clinical manifestations, including high-output cardiac failure and hydrocephalus. Advances in prenatal imaging, particularly fetal MRI, have improved early detection, allowing for timely intervention. Endovascular techniques, especially transarterial embolization, have become the primary treatment modality, often preferred over surgical approaches due to their effectiveness and lower risk. However, challenges remain, particularly in managing these malformations in neonates and infants, where the risk of complications is high. Gamma Knife radiosurgery offers a non-invasive alternative for select cases, though its effects are gradual and may carry delayed risks. Despite advancements, the management of VOGMs continues to require a multidisciplinary approach, with ongoing research focused on improving outcomes through a better understanding of the genetic and molecular underpinnings of the disease. Future directions include the integration of genetic studies into clinical practice and the refinement of treatment strategies to optimize outcomes for this complex condition.

Adelola Adeyole (1935-2021): Early descriptor of congenital dermoid or epidermoid inclusion cyst over the anterior fontanelle and below the galea aponeurotica.

The author wished to detail the life and contributions of Dr. Adelola Adeloye, MBBS, MS, FWCS, FRCS, FACS, FRCP, in hope to pay homage to this giant in Global Neurosurgery. Dr. Adelola Adeloye was born on July 18, 1935 in Illesa, Osun State, present-day South-West Nigeria. The Adeloye-Odeku disease is an eponym for a congenital dermoid or epidermoid inclusion cyst (CDIC/CEDIC) over the anterior fontanelle and below the galea aponeurotica. In 1971, Adeloye and Odeku first described these cysts in 18 Nigerian patients. While overall rare and predominantly noted in children, the Adeloye-Odeku disease has been found to impact adults too. In terms of rarity, CDICs make up 0.1-0.5% of cranial tumors and 0.2% of inclusion cysts. CDICs can be distinguished from CEDICs through histopathology as dermoid cysts may contain hair follicles, sweat, sebaceous glands, and teeth, whereas CEDICs usually are only composed of keratinized debris and epidermal tissue. Assumed first to be an African cyst, cases of the Adeloye-Odeku disease were subsequently reported in other ethnic populations: Turkish, Czechs, Slovaks, Chinese, Japanese, Canadians, Saudi Arabians, Indians, Caucasians, Bangladeshis, Spaniards, and Brazilians.

Practical pearls for management of cranial injury in the developing world.

Traumatic brain injury (TBI) remains a leading cause of morbidity and mortality, with approximately 69 million individuals affected globally each year, particularly in low- and middle-income countries (LMICs) where neurosurgical resources are limited. The neurocognitive consequences of TBI range from life-threatening conditions to more subtle impairments such as cognitive deficits, impulsivity, and behavioral changes, significantly impacting patients' reintegration into society. LMICs bear about 70% of the global trauma burden, with causes of TBI differing from high-income countries (HICs). The lack of equitable neurosurgical care in LMICs exacerbates these challenges. Improving TBI care in LMICs requires targeted resource allocation, neurotrauma registries, increased education, and multidisciplinary approaches within trauma centers. Reports from successful neurotrauma initiatives in low-resource settings provide valuable insights into safe, adaptable strategies for managing TBI when "gold standard" protocols are unfeasible. This review discusses common TBI scenarios in LMICs, highlighting key epidemiological factors, diagnostic challenges, and surgical techniques applicable to resource-limited settings. Specific cases, including epidural hematoma, subdural hematoma, subarachnoid hemorrhage, and cerebrospinal fluid leaks, are explored to provide actionable insights for improving neurosurgical outcomes in LMICs.

Interleukin 6 and cancer resistance in glioblastoma multiforme.

Despite unprecedented survival in patients with glioblastoma (GB), the aggressive primary brain cancer remains largely incurable and its mechanisms of treatment resistance have gained particular attention. The cytokine interleukin 6 (IL-6) and its receptor weave through the hallmarks of malignant gliomas and may represent a key vulnerability to GB. Known for activating the STAT3 pathway in autocrine fashion, IL-6 is amplified in GB and has been recognized as a negative biomarker for GB prognosis, rendering it a putative target of novel GB therapies. While it has been recognized as a biologically active component of GB for three decades only with concurrent advances in understanding of complementary immunotherapy has the concept of targeting IL-6 for a human clinical trial gained scientific footing.

Arachnoid cysts and epilepsy: seizures and epileptogenesis.

Arachnoid cysts are sacs within the arachnoid membrane, filled with cerebrospinal fluid, and overwhelmingly asymptomatic; however, they can also lead to neurological symptoms such as epilepsy. The dependence of AC on epilepsy has been a subject of controversy because of studies with mixed results on whether AC contributes to seizure activity. This is a narrative review for the synthesis of available present research on the pathophysiological mechanisms of epilepsy, clinical presentation, and treatment options in patients with epilepsy and ACs. Some find no impactful association between ACs and seizures, while others point out the probable role of ACs in Epileptogenesis. Endoscopic fenestration and similar surgical interventions were found quite effective at reducing the frequency of seizures for selected patients, although not all of them achieve complete seizure control. Such a decision needs to be tailored on the basis of considerations such as localization and size of cysts and general health conditions. Future research should investigate the genetic and molecular basis of ACs and, based on large prospective long-term studies, define the AC-epilepsy relationship and refine treatment strategies in affected individuals.

A call for clinical trials in glioblastoma multiforme for interleukin 4, interleukin 6, interleukin 13 and CD40.

Glioblastoma multiforme (GBM) is one of the most aggressive and deadly forms of brain cancer, which has a very complex tumor microenvironment (TME) promoting tumor growth, immune evasion, and resistance to therapy. The main players within this environment are represented by cytokines such as Interleukin-4, Interleukin-6, and Interleukin-13, along with the costimulatory molecule CD40. The paper draws back the curtain on the complex interactions played out by these molecules in contributing to the formation of a TME within GBM. IL-4 and IL-13 induce an immunosuppressive environment through the polarization of tumor-associated macrophages (TAMs) into a pro-tumoral M2 phenotype. In contrast, IL-6 takes part in the activation of the JAK-STAT3 pathway, enhancing survival and proliferation of tumor cells. In this context, CD40 either induces anti-tumor immunity through APC activation or facilitates tumors by angiogenesis and survival pathways. The synergistic actions of these molecules create feedback loops that keep up the malignancy of GBM and present a big problem for therapy. Knowledge of these interactions opens new ways for the development of multi-targeted therapeutic strategies at the other end. This may result in the interruption of the tumor-supportive environment in GBM, reducing tumor growth and improving patient outcomes by targeting IL-4, IL-6, IL-13, and CD40 simultaneously.

Rathke's cleft cysts: from pathophysiology to management.

Rathke's cleft cysts (RCCs) are benign, non-neoplastic lesions located in the sellar and suprasellar regions of the brain, originating from remnants of Rathke's pouch, an embryonic precursor to the anterior pituitary gland. Although RCCs are frequently asymptomatic and discovered incidentally during imaging studies, they can present with a variety of symptoms, including headaches, visual disturbances, and endocrine dysfunction due to the compression of adjacent neural structures. The management of RCCs is particularly challenging, as the decision to pursue conservative monitoring or surgical intervention depends heavily on the cyst's size, growth potential, and the severity of symptoms. Transsphenoidal surgery is the primary treatment for symptomatic RCCs, offering effective relief from symptoms through decompression of the cyst. However, recurrence remains a significant issue, with rates reported up to 33%, prompting debates about the extent of cyst wall removal during surgery. Recent advancements in minimally invasive endoscopic techniques have improved surgical outcomes, yet the risk of postoperative complications such as hypopituitarism and cerebrospinal fluid leaks persists. Additionally, stereotactic radiosurgery has emerged as a potential alternative for patients with recurrent RCCs or those who are not suitable candidates for repeat surgery. Despite its promise, the long-term safety and efficacy of radiotherapy in RCC management require further investigation. This narrative review aims to provide a comprehensive overview of RCCs, integrating the latest research and clinical guidelines to discuss pathophysiology, clinical presentation, and management strategies, emphasizing the need for a personalized approach to treating this complex condition.

Deep brain stimulation for obsessive compulsive disorder: the functional neurosurgeon armamentarium.

Deep brain stimulation (DBS) is a neurosurgical procedure that utilizes implanted electrodes and electrical stimulation for the treatment of neurological disorders. In cases where patients present with severe functional impairment while being refractory to less invasive treatment options, DBS is considered "gold standard." Still, DBS-related work is still widely under investigation, with ethical issues arising that may impact a patient's physical and psycho-social status. These include patient selection, informed consent, patient autonomy, pre-operation counseling and professional psycho-social preparation and follow-up support. Bioethicists and philosophers have increasingly worked together with in clinicians and researchers to identify, address and present ethical consideration in both clinical practice and research to balance the risk-benefit ratio in DBS treatment for obsessive-compulsive disorder.

Neurosurgeons in Congress: the 25th amendment and United States Presidency.

In 2020, realizing that a President was not immune to a public health emergency, United States Speaker of the House Nancy Pelosi recommended the passing of a Bill (Raskin J (2021) A Bill To establish the Commission on Presidential Capacity to Discharge the Powers and Duties of the Office, and for other purposes. 116th Congress, 2nd Session. https://raskin.house.gov/sites/raskin.house.gov/files/Commission%20on%20Presidential%20Capacity%20Act%20%5BFINAL%5Dpdf.pdf ) that would create a bipartisan group of experts to evaluate the Commander-in-Chief's mental and physical health and advise Congress on whether a President could be demoted under the 25th Amendment. Neurosurgeons are equipped to advice Congress in the advent of such a need. The authors aimed to provide a brief history of the 25th amendment during US history and implications for neurosurgeons within the jurisdictions of US Congress.

Circulating biomarkers literature in glioma patient populations.

Liquid biopsy, the process of identifying circulating biomarkers in patients with cancer, has emerged as clinically significant in population screening, tumor status & subclassification, and individualized patient treatment from tumor genotyping. While advances in genome sequencing and mass spectrometry have yielded large datasets available for mining and identified promising biomarkers in breast, melanoma, and lung cancers, among others, challenges persist in identifying biomarkers in neuro-oncology. Despite growing efforts in biomarker research and promise in their emergent clinical potential, there presently exists no validated circulating biomarker test for patients presenting with gliomas, the most common primary brain cancer.

Mildred Codding (1902-1991): Neurosurgery Medical Illustrator at Harvard Medical School, Peter Bent Brigham Hospital, and Boston's Children Hospital.

BACKGROUND: This historical account reviews the life and times of Mildred Codding (1902-1991) in neurosurgery and medical illustration. METHODS: The writing of this project was sparked by the discovery of original scientific and bibliographical information about Codding, testimony on personal relationships, and viewpoints after comprehensive compilation of information. RESULTS: Mildred Codding learned the carbon dust technique from Max Brödel at the Johns Hopkins Hospital (Baltimore, Maryland USA), and worked at Peter Bent Brigham Hospital, now Brigham and Women's Hospital (Boston, Massachusetts, USA). Codding was Dr. Cushing's medical illustrator, colleague, and friend. She provided photographs, diagrams, and sketches for the majority of Cushing's collection of intracranial tumors from 1929 to 1932. A 1991 interview of Codding was hosted by Brigham and Women's Hospital and Boston Children's Hospital for the permanent collection of the Archives of the American Association of Neurologic Surgeons and provides additional photographs and insignia, drawings with pen and ink method, multistepped layering, and illustration implements. Importantly, the Brigham Surgical Alumni insignia showing a surgeon's hand with scalpel was modeled after Codding's left hand. Outside of the operating room, Codding's interests included Pediatrics, Zoology and Genetics, atlantes of surgical operations, teatime, and paint with watercolor, particularly seascapes, lighthouses and dunes. CONCLUSIONS: This article provides glimpses into the personality and marked influence of Mildred Codding on neurosurgery and medical education and adds to the growing literature on her person.

Interleukin 4 and cancer resistance in glioblastoma multiforme.

In this review, the author highlights the role of IL4 in mitigating all the "hallmarks" of cancer growth and resistance to current immunotherapy, providing a framework for its role in GBM as well as guideline for future treatment regimens. This review is organized around six strategies by which IL4 contributes to the immune resistance seen in GBM: (i) apoptosis evasion, (ii) self-sufficiency in growth signals, (iii) insensitivity to anti-growth signals, (iv) invasion and metastasis, (v) limitless replicative potential, (vi) sustained angiogenesis.

Ethics of deep brain stimulation for neuropsychiatric disorders.

Deep Brain Stimulation (DBS) has emerged as a revolutionary neurosurgical technique with significant implications for the treatment of various neuropsychiatric disorders. Initially developed for movement disorders like Parkinson's disease, DBS has expanded to psychiatric conditions such as obsessive-compulsive disorder, depression, anorexia nervosa, dystonia, essential tremor, and Tourette's syndrome. This paper explores the clinical efficacy and ethical considerations of DBS in treating these disorders. While DBS has shown substantial promise in alleviating symptoms and improving quality of life, it raises ethical challenges, including issues of informed consent, patient selection, long-term management, and equitable access to treatment. The irreversible nature of DBS, potential adverse effects, and the high cost of the procedure necessitate a rigorous ethical framework to guide its application. The ongoing evolution of neuromodulation requires continuous ethical analysis and the development of guidelines to ensure that DBS is used responsibly and equitably across different patient populations. This paper underscores the need for a balanced approach that integrates clinical efficacy with ethical considerations to optimize patient outcomes and ensure sustainable practice.

Implications for neurosurgery of medical schools leaving the United States News and World Report.

Ranked lists are a highly praised method of assessment in America. Whether it's a list of the top national sports teams, the best restaurants in New York City, or as in this case, the strongest educational institutions, we look to rankings to scrutinize, evaluate, and compare. Unfortunately, not all rankings offer insightful and valuable information. Many use metrics that fall short of an accurate representation of the desired outcome. The U.S. News & World Report (USNWR), one of the most widely regarded rankings of educational institutions, has recently been under the spotlight as several major medical schools have removed themselves from candidate lists. The current USNWR Medical School's rankings are regarded as having a narrow perspective in that the metrics perpetuate a less diverse medical community and fail to recognize worthy institutions that choose to champion a well-rounded student experience. The authors, along with the many others, fear this may deliver a skewed vision of what the USNWR tries to measure: the excellence of a medical education.

Occipital lobe epilepsy surgery: treating seizures in the posterior cortex.

Occipital lobe epilepsy (OLE) is an uncommon type of extratemporal epilepsy constituting roughly 2-13% of symptomatic partial epilepsies and epilepsy surgery cases. Over two-thirds of patients with OLE present with two characteristics: (1) ictal semiology compatible with an occipital seizure focus (e.g., ictal blindness, visual perceptual disturbance, eye blinking, nystagmus), and (2) lateralizing features referable to the posterior cortex (e.g., visual field defects, contralateral head deviation). The remaining one-third of patients present with ≥ 2 seizure types, indicative of spread to other lobes. A common representation of this cortical spread is the altered mental status and generalized tonic-clonic activity seen in patient with OLE. While the key clinical symptoms include visual hallucinations, it may be difficult to elicit on history, especially from children, and are not always present.

Financial barriers and inequity in medical education in India: challenges to training a diverse and representative healthcare workforce.

India has been historically challenged by an insufficient and heterogeneously clustered distribution of healthcare infrastructure. While resource-limited healthcare settings, such as major parts of India, require multidisciplinary approaches for improvement, one key approach is the recruitment and training of a healthcare workforce representative of its population. This requires overcoming barriers to equity and representation in Indian medical education that are multi-faceted, historical, and rooted in inequality. However, literature is lacking regarding the financial or economic barriers, and their implications on equity and representation in the Indian allopathic physician workforce, which this review sought to describe. Keyword-based searches were carried out in PubMed, Google Scholar, and Scopus in order to identify relevant literature published till November 2023. This state-of-the-art narrative review describes the existing multi-pronged economic barriers, recent and forthcoming changes deepening these barriers, and how these may limit opportunities for having a diverse workforce. Three sets of major economic barriers exist to becoming a specialized medical practitioner in India - resources required to get selected into an Indian medical school, resources required to pursue medical school, and resources required to get a residency position. The resources in this endeavor have historically included substantial efforts, finances, and privilege, but rising barriers in the medical education system have worsened the state of inequity. Preparation costs for medical school and residency entrance tests have risen steadily, which may be further exacerbated by recent major policy changes regarding licensing and residency selection. Additionally, considerable increases in direct and indirect costs of medical education have recently occurred. Urgent action in these areas may help the Indian population get access to a diverse and representative healthcare workforce and also help alleviate the shortage of primary care physicians in the country. Discussed are the reasons for rural healthcare disparities in India and potential solutions related to medical education.