Global Neurosurgery at the 76th World Health Assembly (2023): First Neurosurgery-Driven Resolution Calls for Micronutrient Fortification to Prevent Spina Bifida.

Since 2018, a neurosurgery delegation has been actively engaged and consistently present at the World Health Assembly. Recognizing the growing impact of neurosurgical diseases, the neurosurgery delegation participated in the 76th World Health Assembly in May 2023, advocating for timely, safe, and affordable global neurosurgical care. The delegation focused on forging new collaborations, strengthening the World Health Organization-World Federation of Neurosurgical Societies official relations, and actively supporting resolutions that impact the neurosurgical patients. However, there is a long advocacy journey ahead to address unmet neurosurgical needs. Patient-centered advocacy is an inherent task of our profession and the essence of the Global Neurosurgery Bogota Declaration of 2016. The highlight of the 76th World Health Assembly was the adoption of the first neurosurgery-driven resolution calling for micronutrient fortification to prevent spina bifida and other micronutrient deficiencies. For the last 4 years, the Global Alliance for Prevention of Spina Bifida, a group spearheaded by neurosurgeons, advocated for spina bifida prevention. This Alliance collaborated with many stakeholders, notably, the Colombian government to promote the resolution: "Accelerating efforts for preventing micronutrient deficiencies and their consequences, including spina bifida and other neural tube defects, through safe and effective food fortification." This is a proud milestone for the neurosurgical profession. There are many strategies available for neurosurgeons, when working together with elected leaders, other stakeholders, and allied professionals, to implement initiatives that can prevent future cases of spina bifida and other neurological disorders and reduce the burden of neurosurgical disease.

Barriers and facilitators to the implementation of mandatory folate fortification as an evidence-based policy to prevent neural tube defects.

BACKGROUND: Neural tube defects continue to be one of the main congenital malformations affecting the development of the nervous system and a significant cause of disability and disease burden to individuals living with these conditions. Mandatory food fortification with folic acid is, by far, one of the most efficacious, safe, and cost-effective interventions to prevent neural tube defects. However, most countries fail to effectively fortify staple foods with folic acid, impacting public health and healthcare systems and generating dismal disparities. AIM: This article discusses the main barriers and facilitators for implementing mandatory food fortification as an evidence-based policy to prevent neural tube defects worldwide. METHODS: A comprehensive review of the scientific literature allowed the identification of the determinant factors acting as barriers or facilitators for the reach, adoption, implementation, and scaling up of mandatory food fortification with folic acid as an evidence-based policy. RESULTS: We identified eight barriers and seven facilitators as determinant factors for food fortification policies. The identified factors were classified as individual, contextual, and external, inspired by the Consolidated Framework for Implementation of Research (CFIR). We discuss mechanisms to overcome obstacles and seize the opportunities to approach this public health intervention safely and effectively. CONCLUSIONS: Several determinant factors acting as barriers or facilitators influence the implementation of mandatory food fortification as an evidence-based policy worldwide. Notoriously, policymakers in many countries may lack knowledge of the benefits of scaling up their policies to prevent folic acid-sensitive neural tube defects, improve the health status of their communities, and promote the protection of many children from these disabling but preventable conditions. Not addressing this problem negatively affects four levels: public health, society, family, and individuals. Science-driven advocacy and partnerships with essential stakeholders can help overcome the barriers and leverage the facilitators for safe and effective food fortification.

Global Neurosurgery: Progress and Resolutions at the 75th World Health Assembly.

Neurosurgical advocates for global surgery/neurosurgery at the 75th World Health Assembly gathered in person for the first time after the COVID-19 pandemic in Geneva, Switzerland, in May 2022. This article reviews the significant progress in the global health landscape targeting neglected neurosurgical patients, emphasizing high-level policy advocacy and international efforts to support a new World Health Assembly resolution in mandatory folic acid fortification to prevent neural tube defects. The process of developing global resolutions through the World Health Organization and its member states is summarized. Two new global initiatives focused on the surgical patients among the most vulnerable member states are discussed, the Global Surgery Foundation and the Global Action Plan on Epilepsy and other Neurological Disorders. Progress toward a neurosurgery-inspired resolution on mandatory folic acid fortification to prevent spina bifida-folate is described. In addition, priorities for moving the global health agenda forward for the neurosurgical patient as it relates to the global burden of neurological disease are reviewed after the COVID-19 pandemic.

Global strategies for the prevention of neural tube defects through the improvement of folate status in women of reproductive age.

INTRODUCTION: Neural tube defects represent a global public health problem, mainly in countries where effective prevention strategies are not yet in place. The global prevalence of neural tube defects is estimated at 18.6/10,000 (uncertainty interval: 15.3-23.0) live births, where ~ 75% of cases result in under-five mortality. Most of the mortality burden is in low- and middle-income countries. The main risk factor for this condition is insufficient folate levels in women of reproductive age. METHODS: This paper reviews the extent of the problem, including the most recent global information on folate status in women of reproductive age and the most recent estimates of the prevalence of neural tube defects. Additionally, we provide an overview of the available interventions worldwide to reduce the risk of neural tube defects by improving folate status in the population, including dietary diversification, supplementation, education, and fortification. RESULTS: Large-scale food fortification with folic acid is the most successful and effective intervention to reduce the prevalence of neural tube defects and associated infant mortality. This strategy requires the coordination of several sectors, including governments, the food industry, health services providers, the education sector, and entities that monitor the quality of the service processes. It also requires technical knowledge and political will. An international collaboration between governmental and non-governmental organizations is essential to succeed in saving thousands of children from a disabling but preventable condition. DISCUSSION: We propose a logical model for building a national-level strategic plan for mandatory LSFF with folic acid and explain the actions needed for promoting sustainable system-level change.

The role of neurosurgeons in global public health: the case of folic acid fortification of staple foods to prevent spina bifida.

OBJECTIVE: The global neurosurgery movement arose at the crossroads of unmet neurosurgical needs and public health to address the global burden of neurosurgical disease. The case of folic acid fortification (FAF) of staple foods for the prevention of spina bifida and anencephaly (SBA) represents an example of a new neurosurgical paradigm focused on public health intervention in addition to the treatment of individual cases. The Global Alliance for the Prevention of Spina Bifida-F (GAPSBiF), a multidisciplinary coalition of neurosurgeons, pediatricians, geneticists, epidemiologists, food scientists, and fortification policy experts, was formed to advocate for FAF of staple foods worldwide. This paper serves as a review of the work of GAPSBiF thus far in advocating for universal FAF of commonly consumed staple foods to equitably prevent SBA caused by folic acid insufficiency. METHODS: A narrative review was performed using the PubMed and Google Scholar databases. RESULTS: In this review, the authors describe the impact of SBA on patients, caregivers, and health systems, as well as characterize the multifaceted requirements for proper spina bifida care, including multidisciplinary clinics and the transition of care, while highlighting the role of neurosurgeons. Then they discuss prevention policy approaches, including supplementation, fortification, and hybrid efforts with folic acid. Next, they use the example of FAF of staple foods as a model for neurosurgeons' involvement in global public health through clinical practice, research, education and training, and advocacy. Last, they describe mechanisms for involvement in the above initiatives as a potential academic tenure track, including institutional partnerships, organized neurosurgery, neurosurgical expert groups, nongovernmental organizations, national or international governments, and multidisciplinary coalitions. CONCLUSIONS: The role of neurosurgeons in caring for children with spina bifida extends beyond treating patients in clinical practice and includes research, education and training, and advocacy initiatives to promote context-specific, evidence-based initiatives to public health problems. Promoting and championing FAF serves as an example of the far-reaching, impactful role that neurosurgeons worldwide may play at the intersection of neurosurgery and public health.

Preventing birth defects, saving lives, and promoting health equity: an urgent call to action for universal mandatory food fortification with folic acid.

July 20, 2021 marked the 30th anniversary of the publication of the landmark trial by the British Medical Research Council showing unequivocally that maternal intake of folic acid (vitamin B9) starting before pregnancy prevents most cases of infant spina bifida and anencephaly-two major neural tube defects that are severe, disabling, and often fatal. Mandatory food fortification with folic acid is a safe, cost-effective, and sustainable intervention to prevent spina bifida and anencephaly. Yet few countries implement fortification with folic acid; only a quarter of all preventable spina bifida and anencephaly cases worldwide are currently avoided by food fortification. We summarise scientific evidence supporting immediate, mandatory fortification with folic acid to prevent the development of spina bifida and anencephaly. We make an urgent call to action for the World Health Assembly to pass a resolution for universal mandatory folic acid fortification. Such a resolution could accelerate the slow pace of spina bifida and anencephaly prevention globally, and will assist countries to reach their 2030 Sustainable Development Goals on child mortality and health equity. The cost of inaction is profound, and disproportionately impacts susceptible populations in low-income and middle-income countries.

Patient-Derived Xenotransplant of CNS Neoplasms in Zebrafish: A Systematic Review.

Glioblastoma and neuroblastoma are the most common central nervous system malignant tumors in adult and pediatric populations. Both are associated with poor survival. These tumors are highly heterogeneous, having complex interactions among different cells within the tumor and with the tumor microenvironment. One of the main challenges in the neuro-oncology field is achieving optimal conditions to evaluate a tumor's molecular genotype and phenotype. In this respect, the zebrafish biological model is becoming an excellent alternative for studying carcinogenic processes and discovering new treatments. This review aimed to describe the results of xenotransplantation of patient-derived CNS tumors in zebrafish models. The reviewed studies show that it is possible to maintain glioblastoma and neuroblastoma primary cell cultures and transplant the cells into zebrafish embryos. The zebrafish is a suitable biological model for understanding tumor progression and the effects of different treatments. This model offers new perspectives in providing personalized care and improving outcomes for patients living with central nervous system tumors.

Use of transcranial magnetic stimulation for studying the neural basis of numerical cognition: A systematic review.

Complex numerical cognition is a crucial ability in the human brain. Conventional neuroimaging techniques do not differentiate between epiphenomena and neuronal groups critical to numerical cognition. Transcranial magnetic stimulation (TMS) allows defining causal models of the relationships between specific activated or inhibited neural regions and functional changes in cognition. However, there is insufficient knowledge on the differential effects of various TMS protocols and stimulation parameters on numerical cognition. This systematic review aimed to synthesize the evidence that different TMS protocols provide regarding the neural basis of numerical cognition in healthy adults. We included 21 experimental studies in which participants underwent any transcranial magnetic stimulation such as a single pulse TMS, repetitive TMS, and theta-burst stimulation. The primary outcome measures were any change in numerical cognition processes evidenced by numerical or magnitude tasks, measured with any independent variable like reaction times, accuracy, or congruency effects. TMS applied to regions of the parietal cortex and prefrontal cortex has neuromodulatory effects, which translate into measurable behavioral effects affecting cognitive functions related to arithmetic and numerical and magnitude processing. The use of TMS for the study of the neural bases of numerical cognition allows addressing issues such as localization, timing, lateralization and has allowed establishing site-function dissociations and double site-function dissociations. Moreover, this technique is in a moment of expansion due to the growing knowledge of its physiological effects and the enormous potential of combining TMS with other techniques such as electroencephalography, functional magnetic resonance imaging, or near-infrared spectroscopy to reach a more precise brain mapping.

Desenlace de craniectomía descompresiva primaria y secundaria en pacientes con trauma craneoencefálico severo en la Clínica Universidad de La Sabana / Outcomes of Primary and Secondary Decompressive Craniectomy in Patients with Severe Traumatic Brain Injury at Clínica de la Universidad de La Sabana

RESUMEN Objetivos: El propósito de este estudio fue determinar el desenlace en el egreso y en el seguimiento a un año de los pacientes con trauma craneoencefálico severo sometidos a craniectomía descompresiva primaria y secundaria en la Clínica de la Universidad de La Sabana, en un periodo de cinco años. Pacientes y métodos: Se llevó a cabo una serie de casos retrospectiva de pacientes con trauma craneoencefálico severo sometidos a craniectomía descompresiva entre 2008 y 2013. Los desenlaces primarios fueron la sobrevida y el estado funcional medido por la escala de desenlace de Glasgow al momento del egreso hospitalario y al año de seguimiento. Como desenlaces secundarios se incluyeron el tiempo de latencia para la realización de la craniectomía, las complicaciones intra- y postoperatorias, días de hospitalización y estancia en la unidad de cuidados intensivos, tiempo de ventilación, resultados de la craneoplastia y causa de muerte. Resultados: Treinta y cinco pacientes con trauma craneoencefálico severo fueron sometidos a craniectomía descompresiva en el periodo de estudio, 29 primarias y 6 secundarias, con una latencia mediana de 5 horas y 57 horas, respectivamente. Se observó una sobrevida del 51,4 % de los pacientes, de los cuales 39 % presentó recuperación funcional satisfactoria en la escala de desenlace de Glasgow en el momento del egreso y al año. Conclusiones: En este grupo de pacientes sometidos a craniectomía descompresiva primaria o secundaria, junto con un manejo interdisciplinario y rehabilitación precoz, se presentaron desenlaces funcionales favorables en el seguimiento a largo plazo.

ABSTRACT Aim: The purpose of this study was to determine the outcome, at discharge and at one-year follow-up, of patients with severe traumatic brain injury undergoing primary and secondary decompressive craniectomy at Clinica Universidad de La Sabana, over a period of five years. Patients and methods: We conducted a retrospective case series of patients with severe traumatic brain injury undergoing decompressive craniectomy between 2008 and 2013. Te primary outcomes were survival and functional status, measured by the Glasgow Outcome Scale, both at discharge, and at the one year follow-up. Secondary outcomes included latency time for craniectomy, intra and postoperative complications, days of hospitalization and intensive care unit stay, ventilation time, cranioplasty results, and cause of death. Results: Thirty-five patients with severe traumatic brain injury underwent decompressive craniectomy in the study period, 29 of which were primary and 6, secondary, with a median latency of 5 hours and 57 hours, respectively. A survival of 51.4% of the patients was observed, of which 39% presented satisfactory functional recovery on the Glasgow outcome scale at the time of discharge and one year later. Conclusions: In this group of patients who underwent primary or secondary decompressive craniectomy, together with interdisciplinary management and early rehabilitation, favorable functional outcomes were found in the long-term follow-up.

Central and peripheral nervous system involvement by COVID-19: a systematic review of the pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings.

BACKGROUND: SARS-CoV-2 can affect the human brain and other neurological structures. An increasing number of publications report neurological manifestations in patients with COVID-19. However, no studies have comprehensively reviewed the clinical and paraclinical characteristics of the central and peripheral nervous system's involvement in these patients. This study aimed to describe the features of the central and peripheral nervous system involvement by COVID-19 in terms of pathophysiology, clinical manifestations, neuropathology, neuroimaging, electrophysiology, and cerebrospinal fluid findings. METHODS: We conducted a comprehensive systematic review of all the original studies reporting patients with neurological involvement by COVID-19, from December 2019 to June 2020, without language restriction. We excluded studies with animal subjects, studies not related to the nervous system, and opinion articles. Data analysis combined descriptive measures, frequency measures, central tendency measures, and dispersion measures for all studies reporting neurological conditions and abnormal ancillary tests in patients with confirmed COVID-19. RESULTS: A total of 143 observational and descriptive studies reported central and peripheral nervous system involvement by COVID-19 in 10,723 patients. Fifty-one studies described pathophysiologic mechanisms of neurological involvement by COVID-19, 119 focused on clinical manifestations, 4 described neuropathology findings, 62 described neuroimaging findings, 28 electrophysiology findings, and 60 studies reported cerebrospinal fluid results. The reviewed studies reflect a significant prevalence of the nervous system's involvement in patients with COVID-19, ranging from 22.5 to 36.4% among different studies, without mortality rates explicitly associated with neurological involvement by SARS-CoV-2. We thoroughly describe the clinical and paraclinical characteristics of neurological involvement in these patients. CONCLUSIONS: Our evidence synthesis led to a categorical analysis of the central and peripheral neurological involvement by COVID-19 and provided a comprehensive explanation of the reported pathophysiological mechanisms by which SARS-CoV-2 infection may cause neurological impairment. International collaborative efforts and exhaustive neurological registries will enhance the translational knowledge of COVID-19's central and peripheral neurological involvement and generate therapeutic decision-making strategies. REGISTRATION: This review was registered in PROSPERO 2020 CRD42020193140 Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020193140.

Spontaneous thrombosis of a vein of Galen malformation associated with acute sinusitis: a case report.

The vein of Galen malformation is caused by an abnormal shunting between choroidal arteries and the median prosencephalic vein during embryological development, leading to increased blood flow to the deep cerebral veins, intracranial damage, and systemic repercussions. Idiopathic spontaneous thrombosis of a vein of Galen malformation is rare, and its association with acute sinusitis has not been reported in the literature. We present the case of a girl with a postnatal diagnosis of a vein of Galen malformation at the age of 16 months, with secondary pulmonary hypertension that was adequately controlled with spironolactone. At 3 years old, while expecting elective endovascular treatment, the patient developed spontaneous thrombosis of the vein of Galen malformation, concomitant to an acute sinusitis episode, with complete resolution of the vascular malformation and secondary pulmonary hypertension. The patient continued with normal neurological development over a 5-year follow-up. We discuss the main pathophysiologic mechanisms that can explain spontaneous thrombosis of VOGMs and the patient's outcome. Awareness of different mechanisms that can lead to spontaneous thrombosis can help in the decision-making process and prompt targeted approaches to individual patients with a vein of Galen malformation.

Spinal cord issues in adult patients with MPS: transition of care survey.

PURPOSE: This study aims to raise awareness of the need for research and appropriate guidelines for managing spinal cord issues in adult patients with mucopolysaccharidosis (MPS) and transition of these patients from pediatric to adult care. METHODS: Pediatric/adult neurosurgeons, orthopedic spine surgeons, and treating physicians with expertise in metabolic disorders and spinal cord issues were invited to complete a survey to assess their experience with spinal cord problems in MPS and their opinion on transitioning routes from pediatric to adult care. RESULTS: Twenty specialists completed the survey; 16 had treated spinal cord issues in patients with MPS. Foramen magnum and cervical stenosis (87%), atlanto-axial instability (67%), and lumbar spine instability (33%) were the main spinal cord issues encountered; 28% had treated adult patients for one or more spinal cord issues. In 40% of cases, this concerned an intervention or procedures performed during childhood. The main specialist responsible for the care of adult patients with MPS differed considerably between institutions and included both pediatric and adult specialists (30% pediatric neurosurgeons, 10% pediatric spine orthopedic surgeons, 30% adult spine neurosurgeons, 20% general adult surgeons). The preferred option (> 50%) for the transition of care was an interdisciplinary team of pediatric and adult specialists. CONCLUSIONS: Further work needs to be done to address problems of managing spinal cord issues in adult patients with MPS. Currently, the responsibility for the care of patients with MPS with spinal cord issues is inconsistent. The best strategy for transitioning these patients from pediatric to adult care is likely an interdisciplinary approach.

Gliomas: New Perspectives in Diagnosis, Treatment and Prognosis.

Gliomas are central nervous system tumors originated from glial cells, whose incidence and mortality is expected to rise in coming years, especially in developing countries. Diagnosis and classification of gliomas have largely relied on tumor histopathologic features that provide limited information regarding response to therapy or prognosis. Current treatment of gliomas is surgery combined with chemotherapy and/or radiotherapy. However, many tumors show a high resistance to these interventions, and recurrences are frequent since conventional therapies do not take into account the unique molecular features of different subtypes of glioma. Molecular genetics provide new insights in classifying gliomas and predicting response to therapy that can range from conventional treatments to new revolutionary therapeutic approaches. This article offers a review of the intracellular signaling pathways involved in carcinogenesis of gliomas, as well as a description of new tools for their diagnosis, prognosis, and treatment with a target-oriented approach.

Unique medical issues in adult patients with mucopolysaccharidoses.

The mucopolysaccharidoses are a group of inherited metabolic diseases caused by deficiencies in enzymes involved in the sequential degradation of glycosaminoglycans (GAGs) leading to substrate accumulation in various tissues and organs. GAG accumulation can cause growth retardation and progressive damage to respiratory, cardiovascular, musculoskeletal, nervous, gastrointestinal, auditory, and visual systems. In the past, few people with severe phenotypic mucopolysaccharidosis (MPS) reached adulthood. However, better methods for diagnosis, multi-disciplinary care, and new therapies have extended lifespan, leading to an increasing number of patients surviving beyond childhood. The growing number of adult MPS patients poses significant challenges for clinicians who may not be familiar with the clinical manifestations of MPS. In addition, as new interventions have changed the natural history of these disorders, it is difficult to anticipate both the impact on life expectancy and other complications that may occur as these patients age. Because the MPS disorders are multi-organ diseases, their management requires a coordinated multi-disciplinary approach. Here we discuss the unique pattern of medical issues and multi-organ involvement in adult patients with MPS and identify the challenges that are associated with management of MPS. This review is based on information from an expert investigator meeting with MPS specialists held October 2-4, 2014 in Dublin, Ireland, as well as on current literature searches focusing on MPS and adults.