Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations.

To elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and most severe of congenital brain arteriovenous malformations, we performed an integrated analysis of 310 VOGM proband-family exomes and 336,326 human cerebrovasculature single-cell transcriptomes. We found the Ras suppressor p120 RasGAP (RASA1) harbored a genome-wide significant burden of loss-of-function de novo variants (2042.5-fold, p = 4.79 x 10-7). Rare, damaging transmitted variants were enriched in Ephrin receptor-B4 (EPHB4) (17.5-fold, p = 1.22 x 10-5), which cooperates with p120 RasGAP to regulate vascular development. Additional probands had damaging variants in ACVRL1, NOTCH1, ITGB1, and PTPN11. ACVRL1 variants were also identified in a multi-generational VOGM pedigree. Integrative genomic analysis defined developing endothelial cells as a likely spatio-temporal locus of VOGM pathophysiology. Mice expressing a VOGM-specific EPHB4 kinase-domain missense variant (Phe867Leu) exhibited disrupted developmental angiogenesis and impaired hierarchical development of arterial-capillary-venous networks, but only in the presence of a "second-hit" allele. These results illuminate human arterio-venous development and VOGM pathobiology and have implications for patients and their families.

Analysis of the Caribbean Neurosurgery Workforce: Scope of Practice, Challenges, and Ways Forward.

BACKGROUND: The neurosurgical workforce in the Caribbean and surrounding countries is largely unknown due to the diversity in cultural, linguistic, political, financial disparities, and colonial history between the countries. About 45 neurosurgeons serve 16 million people in the Caribbean Community and Common Market, a trade alliance including most Caribbean nations. We aimed to understand the current scope of neurosurgical workforce in this region while highlighting any system challenges and potential solutions for upscaling the workforce. METHODS: We surveyed neurosurgeons within Caribbean countries and surrounding countries online using qualitative and quantitative methods via Qualtrics. RESULTS: Of the 38 countries within the Caribbean and surrounding countries, 26 (68%) were surveyed and of which 18 (69%) replied. In total, 172 regional neurosurgeons were identified, of which 61 (35%) replied-with a majority of general neurosurgeons (56%). Remarkably, the majority of countries failed to meet the threshold workforce density for safe health care-either expressed by full-time equivalent neurosurgeons or neurosurgical centers (see table). Most neurosurgical practices confirmed receiving or sending medical referrals. If so, most referrals took longer than 8 hours without significant difference regarding the destination. Lastly, challenges confronting neurosurgical advancement were found in the following: technology and equipment (40%), trained personnel (31%), hospital or medical center infrastructure (14%), neurosurgical education, and training (44%). CONCLUSIONS: To our knowledge, this is the first qualitative and quantitative study exploring the current status of the neurosurgical workforce within the Caribbean and surrounding countries. Identifying resources and challenges can contribute to improving regionalized neurosurgical care.

The impact of limited access to electronic medical records on neurosurgical care within the CARICOM countries: A survey and scoping review.

Introduction: Global access to electronic medical records (EMRs) continues to grow, however many countries including those within the Caribbean Community (CARICOM) lack access to this system. Minimal research investigating EMR use in this region exists. Research question: How does limited EMR access impact neurosurgical care within the CARICOM? Materials and methods: The Cochrane Library, EMBASE, Scopus, PubMed/MEDLINE databases, and grey literature were queried for studies addressing this issue within the CARICOM and low- and/or middle-income countries (LMICs). A comprehensive search for hospitals within the CARICOM was performed and responses to a survey inquiring about neurosurgery availability and EMR access within each facility were recorded. Results: 26 out of 87 surveys were returned leading to a response rate of 29.0%. Among the survey respondents, 57.7% stated neurosurgery was provided at their facility; however, only 38.4% admitted to using an EMR system. Paper charting was the primary means of record keeping for the majority of the facilities (61.5%). The most frequently reported barriers stalling EMR implementation were financial limitations (73.6%) and poor internet access (26.3%). A total of 14 articles were included in the scoping review. Results from these studies suggest that limited EMR access contributes to suboptimal neurosurgical outcomes within the CARICOM and LMICs. Discussion and conclusion: This paper is the first to address the impact that limited EMR has on neurosurgical outcomes in the CARICOM. The lack of research addressing this issue also highlights the need for ongoing efforts to increase research output focused on EMR accessibility and neurosurgical outcomes in these countries.

The impact of traumatic brain injury on economic productivity in the Caribbean.

Introduction: Traumatic brain injury (TBI) is a significant cause of morbidity and mortality in the Caribbean as well as globally. Within the Caribbean, the prevalence of TBI is approximately 706 per 100,000 persons - one of the highest rates per capita in the world. Research question: We aim to assess the economic productivity lost due to moderate to severe TBI in the Caribbean. Material and methods: The annual cost of economic productivity lost in the Caribbean from TBI was calculated from four variables: (1) the number of people with moderate to severe TBI of working age (15-64 years), (2) the employment-to-population ratio, (3) the relative reduction in employment for people with TBI, and (4) per capita Gross Domestic Product (GDP). Sensitivity analyses were performed to evaluate whether the uncertainty of the TBI prevalence data result in substantive changes in the productivity losses. Results: Globally, there was an estimated 55 million (95% UI 53, 400, 547 to 57, 626, 214) cases of TBI in 2016 of which 322,291 (95% UI 292,210 to 359,914) were in the Caribbean. Using GDP per capita, we calculated the annual cost of potential productivity losses for the Caribbean to be $1.2 billion. Discussion and conclusion: TBI has a significant impact on economic productivity in the Caribbean. With upwards of $1.2 billion lost in economic productivity from TBI, there is an urgent need for appropriate prevention and management of this disease by upscaling neurosurgical capacity. Neurosurgical and policy interventions are necessary to ensure the success of these patients in order to maximize economic productivity.

Time to Care: Analysis of Time Differences and Outcomes in the Management of Pediatric Traumatic Brain Injury for a High-Income and Lower-Middle-Income Country.

BACKGROUND: Pediatric cranial trauma is the leading cause of acquired death and disability in children worldwide. However, trauma resources vary widely among countries. We sought to compare management and timely access to care between a level 1 U.S. pediatric trauma center and a tertiary referral hospital in a lower-middle-income country to assess whether system and resource differences influence care and outcomes. METHODS: We compared data from 214 pediatric head trauma admissions to Philippine General Hospital (Manila) with 136 children from the TRACK-TBI pediatrics study cohort at Massachusetts General Hospital (MGH). Admitted MGH patients were compared with the Philippine cohort regarding demographics; mechanism of injury; times to neurosurgical consult, imaging, and surgery; in-hospital mortality; and length of hospitalization. RESULTS: Age (9 years), gender distribution (67% male), and presenting Glasgow Coma Scale scores were similar (P = 0.10) between sites. More children had intracranial injury in the Philippine cohort (73% vs. 60%; n = 319) and more underwent neurosurgery (27% vs. 4%). Times to consult, imaging, and surgery were longer in the Philippines (12.3 vs. 6.5, 12.0 vs. 2.8, and 45.4 vs. 5.6 hours, respectively). In-hospital mortality across all admissions was similar between cohorts (3% vs. 0%; P = 0.09), but significantly higher in the most severe Philippines cases (31% vs. 0%, P=0.04). Length of stay was longer (5 vs. 2 days; P < 0.001) in the Philippine cohort. CONCLUSIONS: High-income country status correlated with faster care, shorter hospitalizations, and better outcomes among severe cases. Prompt care through sophisticated trauma system implementation may improve pediatric health in resource-limited settings.

Genetic dysregulation of an endothelial Ras signaling network in vein of Galen malformations.

To elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and severe congenital brain arteriovenous malformation, we performed an integrated analysis of 310 VOGM proband-family exomes and 336,326 human cerebrovasculature single-cell transcriptomes. We found the Ras suppressor p120 RasGAP ( RASA1 ) harbored a genome-wide significant burden of loss-of-function de novo variants (p=4.79×10 -7 ). Rare, damaging transmitted variants were enriched in Ephrin receptor-B4 ( EPHB4 ) (p=1.22×10 -5 ), which cooperates with p120 RasGAP to limit Ras activation. Other probands had pathogenic variants in ACVRL1 , NOTCH1 , ITGB1 , and PTPN11 . ACVRL1 variants were also identified in a multi-generational VOGM pedigree. Integrative genomics defined developing endothelial cells as a key spatio-temporal locus of VOGM pathophysiology. Mice expressing a VOGM-specific EPHB4 kinase-domain missense variant exhibited constitutive endothelial Ras/ERK/MAPK activation and impaired hierarchical development of angiogenesis-regulated arterial-capillary-venous networks, but only when carrying a "second-hit" allele. These results illuminate human arterio-venous development and VOGM pathobiology and have clinical implications.

Access to training in neurosurgery (Part 1): Global perspectives and contributing factors of barriers to access.

Introduction: Neurological disorders are one of the leading causes of death and disability adjusted life years (DALYs). Efforts have been made to increase the neurosurgical workforce in an attempt to address the global disease burden. Despite these efforts, there continues to be a shortage of neurosurgeons in both high-income countries (HICs) and low-and middle-income countries (LMICs). Research question: The aim of the study was to identify the barriers to neurosurgical training in LMICs and HICs. Materials and methods: We administered an electronic survey targeting medical students, neurosurgery residents, and recent neurosurgery graduates from 69 countries in both HICs and LMICs. Questions were framed to assess barriers to training. Results: Of the 198 responses received (31.3% response rate), 72% identified as male, 27% female, and 0.5% as non-binary gender. 33 respondents were from HICs and 165 were from LMICs. 70.1% of respondents reported no availability of dissection labs in their home institutions. There was a significant difference in availability of subspecialty training between LMICs and HMICs (p â€‹= â€‹0.001) but no significance was seen for competitiveness of programs (p â€‹= â€‹0.473). Discussion and conclusion: There are limitations to our study: it is not comprehensive of training programs globally, there is sampling bias, especially among LMICs, and the accuracy of responses is unclear. Nonetheless, our results highlight the need for a deliberate focus on designing and implementing both short and long term goals in tackling barriers to access to neurosurgical training, with a conscientious effort to involve interested stakeholders and governments to invest in the training and education of their neurosurgical workforce.

Access to training in neurosurgery (Part 2): The costs of pursuing neurosurgical training.

Introduction: Opportunities for in-country neurosurgical training are severely limited in LMICs, particularly due to rigorous educational requirements and prohibitive upfront costs. Research question: This study aims to evaluate financial barriers aspiring neurosurgeons face in accessing and completing neurosurgical training, specifically in LMICs, in order to determine the barriers to equitable access to training. Material and methods: In order to assess the financial costs of accessing and completing neurosurgery residency, an electronic survey was administered to those with the most recent experience with the process: aspiring neurosurgeons, neurosurgical trainees, and recent neurosurgery graduates. We attempted to include a broad representation of World Health Organization (WHO) geographic regions and World Bank income classifications in order to determine differences among regions and countries of different income levels. Results: Our survey resulted in 198 unique responses (response rate 31.3%), of which 83% (n â€‹= â€‹165) were from LMICs. Cost data were reported for 48 individual countries, of which 26.2% were reported to require trainees to pay for their neurosurgical training. Payment amounts varied amongst countries, with multiple countries having costs that surpassed their annual gross national income as defined by the World Bank. Discussion and conclusions: Opportunities for formal neurosurgical training are severely limited, especially in LMICs. Cost is an important barrier that can not only limit the capacity to train neurosurgeons but can also perpetuate inequitable access to training. Additional investment by governments and other stakeholders can help develop a sufficient workforce and reduce inequality for the next generation of neurosurgeons worldwide.

Qualitative and Quantitative Analysis of Pediatric Post Neurosurgical Care in a Lower Middle-Income Country: The Zambian Experience.

OBJECTIVE: Pediatric postoperative neurosurgical care is an essential component of a child's treatment pathway. It is important to better understand how neurosurgeons in lower middle-income countries (LMICs) have been able to address socioeconomic and systemic factors to improve their patients' access to quality pediatric postoperative neurosurgical care. We aim to characterize the pediatric neurosurgical postoperative system in place in Zambia and to discuss how these efforts have been implemented to improve outcomes and address socioeconomic barriers to accessing health care. METHODS: We acquired a patient list of 90 tenants of House of Hope (HOH)-an out-of-hospital center caring for children awaiting surgery, as well as those recovering from surgery. Of the patient list, 44 patients qualified for our study. Survey responses and occurrence of demographic and clinical characteristics were calculated. Non-normally distributed variables (age) were reported by median and interquartile range (IQR). Dichotomous variables were presented as percentages. Fisher's Exact test was applied to compare categorical data and hospital re-admission. A P-value of <0.05 was considered significant. RESULTS: Our study demonstrates two key findings: (1) low 30-day hospital re-admission rate of 9% and (2) favorable postoperative experience by patient families. Of the 44 patients, a majority were 1-year-old children (n = 31, 70%) and female (n = 24, 55%) (IQR 1-2 years). Presenting conditions included: hydrocephalus only (n = 35, 80%), hydrocephalus and myelomeningocele (n = 5, 11%), myelomeningocele only (n = 2, 5%), cerebral palsy (n = 1, 2%), and encephalocele (n = 1, 2%). Half (n = 22, 50%) of the patients lived in east Zambia, 8 (18%) lived in central, 8 (18%) in north, 5 (11%) in south, and 1 (2%) in west Zambia. CONCLUSIONS: We report the first qualitative and quantitative analysis of postoperative care for LMIC pediatric neurosurgical patients in the academic literature. Quality, patient-centered postoperative pediatric neurosurgical care that is rooted in addressing socioeconomic determinants of health produces good outcomes in LMICs.

Implementing a Neurotrauma Registry in Latin America and the Caribbean.

Background Traumatic brain injury (TBI) has a disproportionately greater impact in low- and middle-income countries (LMICs). One strategy to reduce the burden of disease in LMICs is through the implementation of a trauma registry that standardizes the assessment of each patient's management of care. Objective This study aims to ascertain the interest of Latin America and the Caribbean (LAC) nations in establishing a shared neurotrauma registry in the regional block, based on an existing framework for collaboration. Methods A descriptive review was performed regarding the interests of LAC nations in implementing a shared neurotrauma registry in their region. We convened a meeting with seven Caribbean and five Latin American nations. Results One hundred percent ( n = 12) of the LAC representatives including neurosurgeons, neurointensivists, ministers of health, and chief medical officers/emergency medical technicians (EMTs) agreed to adopt the registry for tracking the burden of TBI and associated pathologies within the region. Conclusion The implementation of a neurotrauma registry can benefit the region through a shared database to track disease, improve outcomes, build research, and ultimately influence policy.

The unmet global burden of cranial epidural hematomas: A systematic review and meta-analysis.

OBJECTIVE: Approximately 69 million people suffer from traumatic brain injury (TBI) annually. Patients with isolated epidural hematomas (EDH) with access to timely surgical intervention often sustain favorable outcomes. Efforts to ensure safe, timely, and affordable access to EDH treatment may offer tremendous benefits. METHODS: A comprehensive literature search was conducted. A random-effects model was used to pool the outcomes. Studies were further categorized into groups by World Bank Income classification: high-income countries (HICs) and low- and middle-income countries (LMICs). RESULTS: Forty-nine studies were included, including 36 from HICs, 12 from LMICs, and 1 from HIC / LMIC. Incidence of EDH amongst TBI patients 8.2 % (95 % CI: 5.9,11.2), including 9.2 % (95 %CI 6.4,13.2) in HICs and 5.8 % (95 % CI: 3.1,10.7) in LMICs (p = 0.20). The overall percent male was 73.7 % and 47.4 % were caused by road traffic accidents. Operative rate was 76.0 % (95 %CI: 67.9,82.6), with a numerically lower rate of 74.2 % (95 %CI: 64.0,81.8) in HICs than in LMICs 82.9 % (95 %CI: 65.4,92.5) (p = 0.33). This decreased to 55.5 % after adjustment for small study effect. The non-operative mortality (5.3 %, 95 %CI: 2.2,12.3) was lower than the operative mortality (8.3 %, 95 %CI: 4.6,14.6), with slightly higher rates in HICs than LMICs. This relationship remained after adjustment for small study effect, with 9.3 % operative mortality compared to 6.9 % non-operative mortality. CONCLUSION: With an overall EDH incidence of 8.2 % and an operative rate of 55.5 %, 3.1 million people worldwide require surgery for traumatic EDH every year, most of whom are in prime working age. Given the favorable prognosis with treatment, traumatic EDH is a strong investment for neurosurgical capacity building.

Racial and Social Determinants of Civilian Gunshot Wounds to the Head.

Objective: To assess the clinical, racial, and social characteristics of victims of Gunshot wounds (GSWs) to the head and assess for associations between these factors and outcomes. Summary Background Data: Previous literature has not focused on the association of race and socioeconomic factors with these specific injuries. Methods: We identified patients with GSWs to the head who presented to 2 urban academic medical centers between 1998 and 2020, and extracted patient-level demographic data, information about the clinical and surgical course, and outcomes at discharge and follow-up. Results: The cohort included 250 patients, 90% (n = 226) of whom were male, with a mean age of 28 years. Forty-five percent were white (n = 112), 19% Black (n = 48), 18% Latinx (n = 45), with 6% "other" (n = 16), and 12% "unknown" (n = 29). The majority of patients presented with assault-related trauma (n = 153, 61%) as compared to self-inflicted injuries (n = 97, 39%). Across the entire cohort, sex, age, race, and median income by ZIP code were not significant predictors of outcome. Victims of assault by GSW to the head were more likely to be age 18 or younger (OR 5.26, P = 0.01), between the ages of 19 and 33 years (OR 4.7, P = 0.001), Black (OR 6.66, P < .001), and Latinx (OR 2.65, P = 0.03). Most patients (n = 155, 63%) had a poor functional outcome (modified Rankin Score 3-6) at discharge. Conclusion: Age, race, and income status were not independent predictors of mortality or functional outcome at discharge in our population. Assault-related GSWs to the head mostly involved young Black or Latinx men of lower socioeconomic status, while self-inflicted injuries were largely seen in older white men.

The Governance of Helmet Safety to Prevent Traumatic Brain Injury in the Caribbean.

BACKGROUND: The Caribbean is a unique region of islands and cays home to nearly 43 million people. A significant challenge facing this population is the burden of traumatic brain injury, which disproportionately affects younger individuals and carries a significant economic burden. A preventive measure to reduce this burden is consistent wearing of helmets. This study aims to assess TBI prevention through helmet safety in Caribbean nations in order to demonstrate the regional impact of public health solutions. METHODS: We assess the member states of the Caribbean Community (CARICOM) and sought to evaluate CARICOM nations' TBI prevention through helmet safety with relation to public health, policy, laws, infrastructure, and regulations. We produced the Rolle Scoring System (RSS) to ascertain the influence of governance around helmet safety for TBI prevention. The RSS aims to provide a quantifiable method of how well a CARICOM nation is performing in efforts to reduce TBI. The RSS is broken down into 2 categories, with scores ranging from 1 (worst) to 5 (best). The range of possible scores a CARICOM nation could receive was 8 to 40. RESULTS: Fourteen CARICOM nations were ultimately incorporated into our analysis. From the initial cohort, 3 were removed. These nations were Anguilla, Saint Kitts & Nevis, and Montserrat. We analyzed values derived from the RSS, finding a mean Rolle score of 22. We further subdivided the nations into low Rolle score (8-24) and high Rolle score (>24). Trinidad and Tobago had the highest Rolle score at 29. Haiti was found to have the lowest Rolle score at 8. CONCLUSION: Several Caribbean nations have demonstrated leadership pertaining to TBI prevention through helmet safety. The regional momentum of helmet safety in the Caribbean can serve as a model for other geographical regional blocs that share interests and culture to consider comprehensive approaches to public health challenges.

An Assessment of Global Neurotrauma Prevention and Care Delivery: The Provider Perspective.

BACKGROUND: Neurotrauma is a leading cause of morbidity and mortality around the world. Assessment of injury prevention and prehospital care for neurotrauma patients is necessary to improve care systems. METHODS: A 29-question electronic survey was developed based on the Enhancing the Quality and Transparency Of health Research (EQUATOR) checklist to assess neurotrauma policies and laws related to safety precautions. The survey was distributed to members of World Health Organization regions that were considered to be experienced medical authorities in neurosurgery and traumatic brain injury. RESULTS: There were 82 (39%) responses representing 46 countries. Almost all respondents (95.2%) were within the neurosurgical field. Of respondents, 40.2% were from high-income countries (HICs), and 59.8% were from low- and middle-income countries (LMICs). Motor vehicle accidents were reported as the leading cause of neurotrauma, followed by workplace injury and assault. Of respondents, 84.1% reported having a helmet law in their country. HICs (4.38 ± 0.78) were ranked more likely than LMICs (2.88 ± 1.34; P = 0.0001) to enforce helmet laws on a scale of 1-10. Effectiveness of helmet laws was rated as 3.94 ± 0.95 out of 10. Measures regarding prehospital care varied between HICs and LMICs. Patients in HICs were more likely to use public emergency ambulance transportation (81.8% vs. 42.9%; P = 0.0004). All prehospital personnel having emergency training was also reported to be more likely in HICs than LMICs (60.6% vs. 8.7%; P = 0.0001). CONCLUSIONS: When injuries occur, timely access to neurosurgical care is critical. A focus on prehospital components of the trauma system is paramount, and policymakers can use the information presented here to implement and refine health care systems to ensure safe, timely, affordable, and equitable access to neurotrauma care.

Global neurosurgical workforce density-you cannot improve what you do not measure.

Five million neurosurgical cases go untreated each year. This is in part due to the lack of neurosurgical care providers. The World Federation of Neurosurgical Societies has spearheaded efforts to monitor the number of neurosurgical providers around the globe since 2016. In this perspective, we discuss why, when, and how the neurosurgical workforce should be measured.