An Overview of Global Neurosurgery.

Until recently, surgery had been passed over in the domain of global health, historically being described as "the neglected stepchild of global health." Knowledge of the existing global disparities in neurosurgical care has led to neurosurgery capacity-building efforts especially in low-income and middle-income countries. While many global collaborative projects are currently undertaken with philanthropic support, sustainability and scalability are not likely without governmental adoption of neurosurgery-inclusive national surgical plans. Momentum grows for the global neurosurgery community to develop a global neurosurgery action plan outlining goals, a guiding framework, an execution plan, and indicators for monitoring and evaluation.

Establishing Microsurgery Skills Laboratories in Low- and Middle-income Countries with Integrated Remote Teaching: A Novel Approach.

Microneurosurgical techniques remain crucial for managing neurosurgical diseases, especially in low- and middle-income countries (LMICs) where other advanced treatment modalities are not available. The global distribution of these techniques is uneven due to disparities in infrastructure, equipment, and training. Medical professionals from LMICs face barriers in reaching training centers in high-income countries, as well as in accessing microsurgical techniques. To address these disparities in microsurgery training, we offer free and accessible microsurgery training model by combining the donations of microsurgery kits with a comprehensive support system that includes live-streamed, offline, and in-person assistance within LMICs.

Postgraduate Fellowships, Distant Continuing Education, and Funding in Neurosurgical Education.

Neurosurgical education and training are the essential tenets for the development of a sustainable workforce. However, opportunities for training are limited in most parts of the world due to socioeconomic constraints and an inadequate workforce. This global deficit has triggered a huge drive to expand training opportunities. Although training programs are increasing numerically, most of these programs focus on basic residency training with no opportunities for fellowships and continuing education. Herein, we use the Foundation of International Education in Neurological Surgery as a global success model to elucidate on the role of fellowships, distant continuing education, and funding in neurosurgery.

Partnering with Foundations, Philanthropy, and Universities with Programs Supported by Local Physicians and Eventually Local Physicians Taking Ownership.

This article provides a thorough analysis of the evolution and current state of global neurosurgery, emphasizing the transformative power of partnerships between various stakeholders to address the stark inequities in neurosurgical care, especially in LMICs. It discusses the transition from reliance on short-term medical missions to the development of sustainable, locally led neurosurgical programs through education, training, and infrastructure development. The article highlights the importance of long-term educational exchanges, innovative digital learning platforms, and strategic collaborations with foundations, philanthropic organizations, and academic institutions to build local capacities, enhance global neurosurgical competency, and promote self-sufficiency in neurosurgical care across different regions.

Nongovernmental Organizations in Global Neurosurgery: Foundation for International Education in Neurological Surgery and Solidarity Bridge.

Health care disparities between high-income countries (HICs) and low- and middle-income countries (LMICs) are well established. The focus of the surgical aspect of health was identified in the early twenty-first century, and efforts to provide safe surgical intervention require the shift of resources from HICs to LMICs with specialized surgeons, anesthesiologists, and equipment. This intervention may make a difference on the short run; however, to achieve a long-term self-sustaining surgical service in the region of need, education and training of local physicians is key.

Neuro-molecular perspectives on long COVID-19 impacted cerebrovascular diseases - a role for dipeptidyl peptidase IV.

The coronavirus disease 2019 (COVID-19) has caused immense devastation globally with many outcomes that are now extending to its long-term sequel called long COVID. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects not only lungs, but also the brain and heart in association with endothelial cell dysfunction, coagulation abnormalities, and thrombosis leading to cardio-cerebrovascular health issues. Fatigue, cognitive decline, and brain fog are common neurological symptoms in persisting long COVID. Neurodegenerative processes and SARS-CoV-2 infection manifest overlapping molecular mechanisms, such as cytokine dysregulation, inflammation, protein aggregation, mitochondrial dysfunction, and oxidative stress. Identifying the key molecules in these processes is of importance for prevention and treatment of this disease. In particular, Dipeptidyl peptidase IV (DPPIV), a multifunctional peptidase has recently drawn attention as a potential co-receptor for SARS-CoV-2 infection and cellular entry. DPPIV is a known co-receptor for some other COVID viruses including MERS-Co-V. DPPIV regulates the immune responses, obesity, glucose metabolism, diabetes, and hypertension that are associated with cerebrovascular manifestations including stroke. DPPIV likely worsens persisting COVID-19 by disrupting inflammatory signaling pathways and the neurovascular system. This review highlights the neurological, cellular and molecular processes concerning long COVID, and DPPIV as a potential key factor contributing to cerebrovascular dysfunctions following SARS-CoV-2 infection.

Methods in Stroke Prevention in the Wisconsin Native American Population.

Native American individuals are more frequently affected by cerebrovascular diseases including stroke and vascular cognitive decline. The aim of this study was to determine stroke risk factors that are most prevalent in Wisconsin Native Americans and to examine how education at the community and individual level as well as intensive health wellness coaching may influence modification of stroke risk factors. Additionally, we will investigate the role novel stroke biomarkers may play in stroke risk in this population. This paper details the aims and methods employed in the "Stroke Prevention in the Wisconsin Native American Population" (clinicaltrials.gov identifier: NCT04382963) study including participant health assessments, clinical ultrasound exam of the carotid arteries, cognitive testing battery, and structure and execution of the coaching program.

A Novel Approach for Free, Affordable, and Sustainable Microsurgery Laboratory Training for Low- and Middle-Income Countries: University of Wisconsin-Madison Microneurosurgery Laboratory Experience.

BACKGROUND AND OBJECTIVES: In low- and middle-income countries (LMICs), approximately 5 million essential neurosurgical operations per year remain unaddressed. When compared with high-income countries, one of the reasons for this disparity is the lack of microsurgery training laboratories and neurosurgeons trained in microsurgical techniques. In 2020, we founded the Madison Microneurosurgery Initiative to provide no-cost, accessible, and sustainable microsurgery training opportunities to health care professionals from LMICs in their respective countries. METHODS: We initially focused on enhancing our expertise in microsurgery laboratory training requirements. Subsequently, we procured a wide range of stereo microscopes, light sources, and surgical instrument sets, aiming to develop affordable, high-quality, and long-lasting microsurgery training kits. We then donated those kits to neurosurgeons across LMICs. After successfully delivering the kits to designated locations in LMICs, we have planned to initiate microsurgery laboratory training in these centers by providing a combination of live-streamed, offline, and in-person training assistance in their institutions. RESULTS: We established basic microsurgery laboratory training centers in 28 institutions across 18 LMICs. This was made possible through donations of 57 microsurgery training kits, including 57 stereo microscopes, 2 surgical microscopes, and several advanced surgical instrument sets. Thereafter, we organized 10 live-streamed microanastomosis training sessions in 4 countries: Lebanon, Paraguay, Türkiye, and Bangladesh. Along with distributing the recordings from our live-streamed training sessions with these centers, we also granted them access to our microsurgery training resource library. We thus equipped these institutions with the necessary resources to enable continued learning and hands-on training. Moreover, we organized 7 in-person no-cost hands-on microanastomosis courses in different institutions across Türkiye, Georgia, Azerbaijan, and Paraguay. A total of 113 surgical specialists successfully completed these courses. CONCLUSION: Our novel approach of providing microsurgery training kits in combination with live-streamed, offline, and in-person training assistance enables sustainable microsurgery laboratory training in LMICs.

Lumen segmentation using a Mask R-CNN in carotid arteries with stenotic atherosclerotic plaque.

In patients at high risk for ischemic stroke, clinical carotid ultrasound is often used to grade stenosis, determine plaque burden and assess stroke risk. Analysis currently requires a trained sonographer to manually identify vessel and plaque regions, which is time and labor intensive. We present a method for automatically determining bounding boxes and lumen segmentation using a Mask R-CNN network trained on sonographer assisted ground-truth carotid lumen segmentations. Automatic lumen segmentation also lays the groundwork for developing methods for accurate plaque segmentation, and wall thickness measurements in cases with no plaque. Different training schemes are used to identify the Mask R-CNN model with the highest accuracy. Utilizing a single-channel B-mode training input, our model produces a mean bounding box intersection over union (IoU) of 0.81 and a mean lumen segmentation IoU of 0.75. However, we encountered errors in prediction when the jugular vein is the most prominently visualized vessel in the B-mode image. This was due to the fact that our dataset has limited instances of B-mode images with both the jugular vein and carotid artery where the vein is dominantly visualized. Additional training datasets are anticipated to mitigate this issue.

Status of Maternal Cardiovascular Health in American Indian and Alaska Native Individuals: A Scientific Statement From the American Heart Association.

Cardiovascular disease is the leading cause of pregnancy-related death in the United States. American Indian and Alaska Native individuals have some of the highest maternal death and morbidity rates. Data on the causes of cardiovascular disease-related death in American Indian and Alaska Native individuals are limited, and there are several challenges and opportunities to improve maternal cardiovascular health in this population. This scientific statement provides an overview of the current status of cardiovascular health among American Indian and Alaska Native birthing individuals and causes of maternal death and morbidity and describes a stepwise multidisciplinary framework for addressing cardiovascular disease and cerebrovascular disease during the preconception, pregnancy, and postpartum time frame. This scientific statement highlights the American Heart Association's factors for cardiovascular health assessment known collectively as Life's Essential 8 as they pertain to American Indian and Alaska Native birthing individuals. It summarizes the impact of substance use, adverse mental health conditions, and lifestyle and cardiovascular disease risk factors, as well as the cascading effects of institutional and structural racism and the historical trauma faced by American Indian and Alaska Native individuals. It recognizes the possible impact of systematic acts of colonization and dominance on their social determinants of health, ultimately translating into worse health care outcomes. It focuses on the underreporting of American Indian and Alaska Native disaggregated data in pregnancy and postpartum outcomes and the importance of engaging key stakeholders, designing culturally appropriate care, building trust among communities and health care professionals, and expanding the American Indian and Alaska Native workforce in biomedical research and health care settings to optimize the cardiovascular health of American Indian and Alaska Native birthing individuals.

Pathophysiology, cellular and molecular mechanisms of large and small vessel diseases.

Cerebrovascular disease (CVD) is the second most common cause of cognitive impairment and dementia in aged population. CVD presents in a myriad number of clinical ways based on the functional location of pathology. While primary clinical emphasis has been placed on motor, speech and visual deficits, vascular cognitive decline is a vastly under recognized and devastating condition afflicting millions of Americans. CVD, a disease of the blood vessels that supply blood to brain involves an integration between small and large vessels. Cerebral large vessel diseases (LVD) are associated with atherosclerosis, artery-to-artery embolism, intracardiac embolism and a large vessel stroke leading to substantial functional disability. Cerebral small vessel disease (SVD) is critically involved in stroke, brain hemorrhages, cognitive decline and functional loss in elderly patients. An evolving understanding of cellular and molecular mechanisms emphasizes that inflammatory vascular changes contribute to systemic pathologic conditions of the central nervous systems (CNS), with specific clinical presentations including, cognitive decline. Advances in an understanding of pathophysiology of disease processes and therapeutic interventions may help improve outcomes. This review will focus on large and small vessels diseases and their relationship to vascular cognitive decline, atherosclerosis, stroke, and inflammatory neurodegeneration. We will also emphasize the molecular and cellular mechanisms, as well as genetic and epigenetic factors associated with LVD and SVD.

Transcranial Color-Coded Doppler Cerebral Hemodynamics Following Aerobic Exercise Training: Outcomes From a Pilot Randomized Clinical Trial.

Introduction: An active lifestyle with regular exercise is thought to decrease or delay the onset of Alzheimer dementia through increasing blood flow to the brain. We examined the mean flow velocity (MFV) and pulsatility index (PI) in the middle cerebral arteries of individuals randomized into two groups-a Usual Physical Activity (UPA) group and an Enhanced Physical Activity (EPA) exercise intervention group-to determine if exercise training is related to changes in cerebral blood flow. Methods: We examined 23 participants, randomized into a UPA group (n=12) and an EPA group (n=11), with transcranial color-coded Doppler (TCCD) and cardiorespiratory fitness (VO2peak, mL/kg/min) testing at baseline and following a 26-week intervention. TCCD was used to measure MFV and PI. Participants in the EPA group completed supervised aerobic exercise training for 26 weeks. Kendall's tau b correlation was used to examine relationships between variables. The Wilcoxon Rank Sum tests were used to examine changes between the UPA and EPA groups. Results: There was no significant change in MFV or PI in the UPA group or the EPA group (p-values >0.05) between baseline and 26 weeks; the change between the UPA and EPA groups was also not significant (p=0.603). There was no evidence of an association between change in VO2peak and change in MFV or PI (all p-values >0.05). Participants in the EPA group significantly increased their VO2peak compared to the UPA group (p=0.027). Conclusion: This study did not demonstrate evidence of a significant change in the MFV in the middle cerebral arteries or evidence of a significant change in the PI between UPA and EPA groups. Future studies should be performed in larger cohorts and should consider use of personalized exercise programs to maximize understanding of how cerebrovascular hemodynamics change in structure and function with exercise for adults at risk for Alzheimer dementia.

Enhanced expression of pentraxin-3 in glioblastoma cells correlates with increased invasion and IL8-VEGF signaling axis.

Glioblastoma (GB) is highly invasive and resistant to multimodal treatment partly due to distorted vasculature and exacerbated inflammation. The aggressiveness of brain tumors may be attributed to the dysregulated release of angiogenic and inflammatory factors. The glycoprotein pentraxin-3 (PTX3) is correlated with the severity of some cancers. However, the mechanism responsible for the invasive oncogenic role of PTX3 in GB malignancy remains unclear. In this study, we examined the role of PTX3 in GB growth, angiogenesis, and invasion using in vitro and in vivo GB models, proteomic profiling, molecular and biochemical approaches. Under in vitro conditions, PTX3 over-expression in U87 cells correlated with cell cycle progression, increased migratory potential, and proliferation under hypoxic conditions. Conditioned media containing PTX3 enhanced the angiogenic potential of endothelial cells. While silencing of PTX3 by siRNA decreased the proliferation, migration, and angiogenic potential of U87 cells in vitro. Importantly, PTX3 over-expression increased tumor growth, angiogenesis, and invasion in an orthotopic mouse model. Higher levels of PTX3 in these tumors were associated with the upregulation of inflammatory and angiogenic markers including interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF), but decreased levels of thrombospondin-1, an anti-angiogenic factor. Mechanistically, exogenous production of PTX3 triggered an IKK/NFκB signaling pathway that enhances the expression of the motility genes AHGEF7 and Rac1. Taken together, PTX3 expression is dysregulated in GB. PTX3 may augment invasion through enhanced angiogenesis in the GB microenvironment through the IL8-VEGF axis. Thus, PTX3 may represent a potential therapeutic target to mitigate the aggressive behavior of gliomas.

MicroRNA miR-21 Decreases Post-stroke Brain Damage in Rodents.

Due to their role in controlling translation, microRNAs emerged as novel therapeutic targets to modulate post-stroke outcomes. We previously reported that miR-21 is the most abundantly induced microRNA in the brain of rodents subjected to preconditioning-induced cerebral ischemic tolerance. We currently show that intracerebral administration of miR-21 mimic decreased the infarct volume and promoted better motor function recovery in adult male and female C57BL/6 mice subjected to transient middle cerebral artery occlusion. The miR-21 mimic treatment is also efficacious in aged mice of both sexes subjected to focal ischemia. Mechanistically, miR-21 mimic treatment decreased the post-ischemic levels of several pro-apoptotic and pro-inflammatory RNAs, which might be responsible for the observed neuroprotection. We further observed post-ischemic neuroprotection in adult mice administered with miR-21 mimic intravenously. Overall, the results of this study implicate miR-21 as a promising candidate for therapeutic translation after stroke.

Neurosurgery residency and fellowship education in the United States: 2 decades of system development by the One Neurosurgery Summit organizations.

The purpose of this report is to chronicle a 2-decade period of educational innovation and improvement, as well as governance reform, across the specialty of neurological surgery. Neurological surgery educational and professional governance systems have evolved substantially over the past 2 decades with the goal of improving training outcomes, patient safety, and the quality of US neurosurgical care. Innovations during this period have included the following: creating a consensus national curriculum; standardizing the length and structure of neurosurgical training; introducing educational outcomes milestones and required case minimums; establishing national skills, safety, and professionalism courses; systematically accrediting subspecialty fellowships; expanding professional development for educators; promoting training in research; and coordinating policy and strategy through the cooperation of national stakeholder organizations. A series of education summits held between 2007 and 2009 restructured some aspects of neurosurgical residency training. Since 2010, ongoing meetings of the One Neurosurgery Summit have provided strategic coordination for specialty definition, neurosurgical education, public policy, and governance. The Summit now includes leadership representatives from the Society of Neurological Surgeons, the American Association of Neurological Surgeons, the Congress of Neurological Surgeons, the American Board of Neurological Surgery, the Review Committee for Neurological Surgery of the Accreditation Council for Graduate Medical Education, the American Academy of Neurological Surgery, and the AANS/CNS Joint Washington Committee. Together, these organizations have increased the effectiveness and efficiency of the specialty of neurosurgery in advancing educational best practices, aligning policymaking, and coordinating strategic planning in order to meet the highest standards of professionalism and promote public health.

Hydrocephalus Following Giant Transosseous Vertex Meningioma Resection.

Introduction Meningiomas are among the most common primary intracranial tumors. While well-described, there is limited information on the outcomes and consequences following treatment of giant-sized vertex-based meningiomas. These meningiomas have specific risks and potential complications due to their size, location, and involvement with extracalvarial soft tissue and dural sinuses. Herein, we present four giant-sized vertex transosseous meningioma cases with involvement and occlusion of the sagittal sinus, that postoperatively developed external hydrocephalus and ultimately required shunting. Methods A retrospective chart review identified patients with large vertex meningiomas that were: (1) large (>6 cm) with hemispheric (no skull base) location, (2) involvement of the superior sagittal sinus resulting in complete sinus occlusion, (3) involvement of dura resulting in a large duraplasty area, (4) transosseous involvement requiring a 5 cm or larger craniectomy for resection of invaded calvarial bone. Results Tumors were resected in all four cases, with all patients subsequently developing external hydrocephalus which required shunting within 2 weeks to 6 months postsurgery. Conclusion We believe this may be the first report of the development of hydrocephalus following surgical resection of these large lesions. Based on our observations, we propose that a combination of superior sagittal sinus occlusion and changes in brain elasticity and compliance affect the brain's CSF absorptive capacity, which ultimately lead to hydrocephalus development. We suggest that neurosurgeons be aware that postoperative hydrocephalus can quickly develop following treatment of giant-sized vertex-based meningiomas, and that correction of hydrocephalus with shunting can readily be achieved.

Galectin-3 protects against ischemic stroke by promoting neuro-angiogenesis via apoptosis inhibition and Akt/Caspase regulation.

Post-stroke neurological deficits and mortality are often associated with vascular disruption and neuronal apoptosis. Galectin-3 (Gal3) is a potent pro-survival and angiogenic factor. However, little is known about its protective role in the cerebral ischemia/reperfusion (I/R) injury. We have previously shown significant up-regulation of Gal3 in the post-stroke rat brain, and that blocking of Gal3 with neutralizing antibody decreases the cerebral blood vessel density. Our current study demonstrates that intracerebral local delivery of the Gal3 into rat brain at the time of reperfusion exerts neuroprotection. Ischemic lesion volume and neuronal cell death were significantly reduced as compared with the vehicle-treated MCAO rat brains. Gal3 increased vessel density and neuronal survival after I/R in rat brains. Importantly, Gal3-treated groups showed significant improvement in motor and sensory functional recovery. Gal3 increased neuronal cell viability under in vitro oxygen-glucose deprivation conditions in association with increased phosphorylated-Akt, decreased phosphorylated-ERK1/2, and reduced caspase-3 activity. Gene expression analysis showed down regulation of pro-apoptotic and inflammatory genes including Fas-ligand, and upregulation of pro-survival and pro-angiogenic genes including Bcl-2, PECAM, and occludin. These results indicate a key role for Gal3 in neuro-vascular protection and functional recovery following ischemic stroke through modulation of angiogenic and apoptotic pathways.

Surgical approaches for resection of third ventricle colloid cysts: meta-analysis.

Although outcome studies and systematic reviews have been published on the surgical treatment of third ventricle colloid cysts (TVCC), there are no meta-analyses that compare the outcomes for various surgical approaches. This meta-analysis assesses the outcomes and complications for transcortical, transcallosal, and endoscopic surgical approaches used to excise TVCCs. A meta-analysis of surgically excised TVCCs was performed with an assessment of outcome for transcortical, transcallosal, and endoscopic approaches. A random-effects model analyzed the extent of surgical excision. The analysis included reports that compared at least two of these surgical approaches, for a total of 11 studies comprising a population of 301 patients. The transcortical approach was associated with a higher incidence of complete excision compared to the endoscopic approach (OR = 0.137, p = 0.041), with no significant differences observed between transcortical and transcallosal approaches, and between transcallosal and endoscopic approaches. Comparison between endoscopic and pooled microsurgical approaches was also insignificant (OR = 0.22, p = 1). The risk of motor weakness was increased with the transcortical approach compared to the endoscopic approach (OR = 6.10, p = 0.018). There were no significant differences between transcortical and transcallosal approaches regarding newly onset seizures, and no significant mortality differences between all three approaches. This study demonstrates that microsurgical approaches are associated with a greater extent of resection compared to endoscopic approaches; however, best results are likely achieved based on the surgeon's expertise, flexibility, and case review.