Combined endovascular embolization and decompressive craniectomy for microsurgical resection of giant ruptured distal anterior cerebral artery aneurysm.

Giant ruptured distal anterior cerebral artery aneurysms are rare, challenging pathologies that may require a combination of microsurgical and endovascular techniques for optimal treatment [1-9]. We describe the case of a female in her 40 s who presented with a Hunt-Hess 4, Fisher 4 subarachnoid hemorrhage from a multiply ruptured, giant distal anterior cerebral artery aneurysm. The patient underwent coil and n-BCA glue embolization of the aneurysm and its feeding A2 anterior cerebral artery. She subsequently underwent decompressive craniectomy, intracerebral hematoma evacuation, and microsurgical trapping and resection of the aneurysm. Postoperative imaging demonstrated no further aneurysm filling, complete hematoma evacuation, and good decompression. The technical considerations and literature for the combined treatment of large and giant ruptured aneurysms are reviewed. The case presentation, operative nuances, and postoperative course with imaging are reviewed with detailed anatomical diagrams to orient the viewer. The patient consented to the procedure and to the publication of her imaging.

Federal and foundational research funding trends for cerebrovascular neurosurgeons: the decline of the cerebrovascular surgeon-scientist?

OBJECTIVE: The number of cerebrovascular (CV) surgeons has grown with the rise of endovascular neurosurgery. However, it is unclear whether the number of CV surgeon-scientists has concomitantly increased. With increasing numbers of CV neurosurgeons in the US workforce, the authors analyzed associated changes in National Institutes of Health (NIH) and Neurosurgery Research and Education Foundation (NREF) funding trends for CV surgeons over time. METHODS: Publicly available data were collected on currently practicing academic CV surgeons in the US. Inflation-adjusted NIH funding between 2009 and 2021 was surveyed using NIH RePORTER and Blue Ridge Institute for Medical Research data. The K12 Neurosurgeon Research Career Development Program and NREF grant data were queried for CV-focused grants. Pearson R correlation, chi-square analysis, and the Mann-Whitney U-test were used for statistical analysis. RESULTS: From 2009 to 2021, NIH funding increased: in total (p = 0.0318), to neurosurgeons (p < 0.0001), to CV research projects (p < 0.0001), and to CV surgeons (p = 0.0018). During this time period, there has been an increase in the total number of CV surgeons (p < 0.0001), the number of NIH-funded CV surgeons (p = 0.0034), and the percentage of CV surgeons with NIH funding (p = 0.370). Additionally, active NIH grant dollars per CV surgeon (p = 0.0398) and the number of NIH grants per CV surgeon (p = 0.4257) have increased. Nevertheless, CV surgeons have been awarded a decreasing proportion of the overall pool of neurosurgeon-awarded NIH grants during this time period (p = 0.3095). In addition, there has been a significant decrease in the number of K08, K12, and K23 career development awards granted to CV surgeons during this time period (p = 0.0024). There was also a significant decline in the proportion of K12 (p = 0.0044) and downtrend in early-career NREF (p = 0.8978) grant applications and grants awarded during this time period. Finally, NIH-funded CV surgeons were more likely to have completed residency less recently (p = 0.001) and less likely to have completed an endovascular fellowship (p = 0.044) as compared with non-NIH-funded CV surgeons. CONCLUSIONS: The number of CV surgeons is increasing over time. While there has been a concomitant increase in the number of NIH-funded CV surgeons and the number of NIH grants awarded per CV surgeon in the past 12 years, there has also been a significant decrease in CV surgeons with K08, K12, and K23 career development awards and a downtrend in CV-focused K12 and early-career NREF applications and awarded grants. The latter findings suggest that the pipeline for future NIH-funded CV surgeons may be in decline.

Cerebral Venous Sinus Thrombosis.

Cerebral venous sinus thrombosis (CVST) is a rare type of stroke indicated by the formation of blood clots within the dural venous sinuses. These are large venous conduits that are situated between the 2 layers of the dura mater which are responsible for draining blood from the brain and returning it to the systemic circulation. Cortical venous thrombosis refers to the blockage of veins on the brain's cortical surface. Cerebral venous thrombosis encompasses both dural and cortical vein occlusions.

Rates of operative intervention and in-hospital mortality following subarachnoid hemorrhage in patients with COVID-19.

OBJECTIVE: COVID-19 had massive effects on the healthcare system and multifactorial implications for the management of intensive care unit and cerebrovascular patients. This study aimed to assess the effect of COVID-19 on the outcomes of patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS: The National Inpatient Sample (NIS) was used to identify patients with nontraumatic SAH (ICD-10 code I60.x). Patients with nonaneurysmal cerebrovascular malformations or traumatic intracranial injuries were excluded. Only patients managed from April to December 2020 were included in the study given the availability of an ICD-10 code for COVID-19. Data on sociodemographic factors, hospital characteristics, comorbidities, NIS SAH Severity Score (NIS-SSS), surgical treatment, and death were acquired. Multivariable analysis was used to assess predictors of both surgical intervention and in-hospital mortality. RESULTS: In total, 6984 patients met the study criteria, 359 (5.1%) of whom had COVID-19. Those with COVID-19 were more likely to be younger and male and had a higher All Patient Refined Diagnosis-Related Groups illness severity subclass, and NIS-SSS. Moreover, patients with COVID-19 were less likely to undergo surgery (10.0% vs 23.6%, OR 0.35, p < 0.0001) and had significantly higher mortality rates (48.2% vs 22.7%, p < 0.0001). When controlling for other variables, COVID-19 was an independent predictor of death (OR 1.67, p = 0.0002). Aneurysm surgery was performed in 1597 patients (317 open and 1280 endovascular procedures). There was no difference between the cohorts positive and negative for COVID-19 in terms of time to surgery or type of surgery. CONCLUSIONS: COVID-19 had significant impacts on patients with nontraumatic SAH. Specifically, patients with COVID-19 were significantly less likely to undergo surgery and had higher in-hospital mortality rates; however, for patients who did undergo procedural intervention, there was no significant difference in the type of intervention. Multiple factors, from medical acuity to healthcare system limitations, may contribute to these findings. Further retrospective research is needed to identify both specific causes of lower intervention rates and other potential nonaneurysmal causes of SAH in patients with COVID-19.

Direct V3 Vertebral Artery Access for Embolization of Partially Thrombosed Fusiform Basilar Trunk Aneurysm: Technical Case Instruction.

BACKGROUND AND IMPORTANCE: Fusiform vertebrobasilar aneurysms carry significant morbidity. Endovascular strategies are preferred; however, unsafe or unfeasible access can call for innovative strategies. CLINICAL PRESENTATION: An octogenarian patient with an enlarging fusiform proximal basilar artery aneurysm causing a sixth nerve palsy was found to have multiple anatomic features that precluded a transradial or transfemoral endovascular approach. She was thus treated with direct microsurgical access of the V3 segment of the vertebral artery for subsequent coil embolization and flow diversion. CONCLUSION: This case introduces a novel combined microsurgical and endovascular strategy for treating a complex partially thrombosed fusiform basilar artery aneurysm. This approach should be reserved only for patients where conventional endovascular access is dangerous or unfeasible.

Resveratrol and its metabolites elicit neuroprotection via high-affinity binding to the laminin receptor at low nanomolar concentrations.

Resveratrol prevents various neurodegenerative diseases in animal models despite reaching only low nanomolar concentrations in the brain after oral administration. In this study, based on the quenching of intrinsic tryptophan fluorescence and molecular docking, we found that trans-resveratrol, its conjugates (glucuronide and sulfate), and dihydro-resveratrol (intestinal microbial metabolite) bind with high affinities (Kd, 0.2-2 nm) to the peptide G palindromic sequence (near glycosaminoglycan-binding motif) of the 67-kDa laminin receptor (67LR). Preconditioning with low concentrations (0.01-10 nm) of these polyphenols, especially resveratrol-glucuronide, protected neuronal cells from death induced by serum withdrawal via activation of cAMP-mediated signaling pathways. This protection was prevented by a 67LR-blocking antibody, suggesting a role for this cell-surface receptor in neuroprotection by resveratrol metabolites.

Microglial TLR4 Mediates White Matter Injury in a Combined Model of Diesel Exhaust Exposure and Cerebral Hypoperfusion.

BACKGROUND: Air pollution particulate matter exposure and chronic cerebral hypoperfusion (CCH) contribute to white matter toxicity through shared mechanisms of neuroinflammation, oxidative stress, and myelin breakdown. Prior studies showed that exposure of mice to joint particulate matter and CCH caused supra-additive injury to corpus callosum white matter. This study examines the role of TLR4 (toll-like receptor 4) signaling in mediating neurotoxicity and myelin damage observed in joint particulate matter and CCH exposures. METHODS: Experiments utilized a novel murine model of inducible monocyte/microglia-specific TLR4 knockout (i-mTLR4-ko). Bilateral carotid artery stenosis (BCAS) was induced surgically to model CCH. TLR4-intact (control) and i-mTLR4-ko mice were exposed to 8 weeks of either aerosolized diesel exhaust particulate (DEP) or filtered air (FA) in 8 experimental groups: (1) control/FA (n=10), (2) control/DEP (n=10), (3) control/FA+BCAS (n=9), (4) control/DEP+BCAS (n=10), (5) i-mTLR4-ko/FA (n=9), (6) i-mTLR4-ko/DEP (n=8), (7) i-mTLR4-ko/FA+BCAS (n=8), and (8) i-mTLR4-ko/DEP+BCAS (n=10). Corpus callosum levels of 4-hydroxynonenal, 8-Oxo-2'-deoxyguanosine, Iba-1 (ionized calcium-binding adapter molecule 1), and dMBP (degraded myelin basic protein) were assayed via immunofluorescence to measure oxidative stress, neuroinflammation, and myelin breakdown, respectively. RESULTS: Compared with control/FA mice, control/DEP+BCAS mice exhibited increased dMBP (41%; P<0.01), Iba-1 (51%; P<0.0001), 4-hydroxynonenal (100%; P<0.0001), and 8-Oxo-2'-deoxyguanosine (65%; P<0.05). I-mTLR4 knockout attenuated responses to DEP/BCAS for all markers. CONCLUSIONS: i-mTLR4-ko markedly reduced neuroinflammation and oxidative stress and attenuated white matter degradation following DEP and CCH exposures. This suggests a potential role for targeting TLR4 signaling in individuals with vascular cognitive impairment, particularly those exposed to substantial ambient air pollution.

Association of carotid endarterectomy at low-volume centers with higher likelihood of major complications and nonroutine discharge.

OBJECTIVE: Carotid artery stenosis (CAS) is associated with an annual stroke risk of 2%-5%, and revascularization with carotid endarterectomy (CEA) can reduce this risk. While studies have demonstrated that hospital CEA volume is associated with mortality and myocardial infarction, CEA volume cutoffs in studies are relatively arbitrary, and no specific analyses on broad complications and discharge disposition have been performed. In this study, the authors systematically set out to identify a cutoff at which CEA procedural volume was significantly associated with major complications and nonroutine discharge. METHODS: Asymptomatic and symptomatic CAS patients undergoing CEA were retrospectively identified in the Nationwide Readmissions Database (2010-2018). The association of CEA volume with outcomes was explored as a continuous variable using locally estimated scatterplot smoothing. The identified volume cutoff was used to generate dichotomous volume cohorts, and multivariate analyses of patient and hospital characteristics were conducted to evaluate the association of CEA volume with major complications and discharge disposition. RESULTS: Between 2010 and 2018, 308,933 asymptomatic and 32,877 symptomatic patients underwent CEA. Analysis of CEA volume with outcomes as a continuous variable demonstrated that an increase in volume was associated with a lower risk until a volume of approximately 7 cases per year (20th percentile). A total of 6702 (2.2%) asymptomatic and 1040 (3.2%) symptomatic patients were treated at the bottom 20% of hospital procedure volume. Increased rates of complications were seen at low-volume centers among asymptomatic (3.66% vs 2.77%) and symptomatic (7.4% vs 6.87%) patients. Asymptomatic patients treated at low-volume centers had an increased likelihood of major complications (OR 1.26, 95% CI 1.07-1.49; p = 0.007) and nonroutine discharge (OR 1.36, 95% CI 1.24-1.50; p < 0.0001). Symptomatic patients treated at low-volume centers were also more likely to experience major complications (OR 1.47, 95% CI 1.07-2.02; p = 0.02) and nonroutine discharge (OR 1.26, 95% CI 1.07-1.47; p = 0.005). Mortality rates were similar between low- and high-volume hospitals among asymptomatic (0.36% and 0.32%, respectively) and symptomatic (1.06% and 1.49%, respectively) patients, while volume was not significantly associated with mortality among asymptomatic (OR 1.06, 95% CI 0.67-1.65; p = 0.81) and symptomatic (OR 0.81, 95% CI 0.43-1.54; p = 0.52) patients in multivariate analysis. CONCLUSIONS: CEA patients, asymptomatic or symptomatic, are at a higher risk of major complications and nonroutine discharge at low-volume centers. Analysis of CEA as a continuous variable demonstrated a cutoff at 7 cases per year, and further study may identify factors associated with improved outcome at the lowest-volume centers.

The effect of COVID-19 on treatment and outcomes following ischemic stroke: A national assessment.

INTRODUCTION: COVID-19 has had innumerable impacts on the healthcare system, both by worsening patient illness and impeding effective and efficient care. Further, COVID-19 has been tied to increased rates of ischemic stroke, particularly among young patients. We utilized a national database to assess associations of COVID-19 with thrombectomy rates, mortality, and discharge disposition among stroke patients. METHODS: Patients were identified from the National Inpatient Sample (NIS, 2020). Inclusion criteria selected for adult ischemic stroke patients; those with venous thrombosis or unspecified cerebral infarction were excluded. Patients were stratified by presence or absence of COVID-19 diagnosis. Outcome variables included mechanical thrombectomy, in-hospital mortality, and discharge disposition. Additional patient demographics, hospital characteristics, and disease severity metrics were collected. Statistical analysis was performed via multivariable logistic regression and log-binary regression. RESULTS: 54,368 patients were included in the study; 2116 (3.89%) were diagnosed with COVID-19. COVID-19 was associated with lower rates of mechanical thrombectomy (OR 0.94, p < 0.0001), higher rates of in-hospital mortality (OR 1.14, p < 0.0001), and unfavorable discharge disposition (OR 1.08, p < 0.0001), even when controlling for illness severity. Other relationships, such as a male predominance among stroke patients with COVID-19, were also identified. CONCLUSION: This study identified a relationship between COVID-19 diagnosis and worse outcomes for each metric assessed, including mechanical thrombectomy rates, in-hospital mortality, and discharge disposition. Several factors might underly this, ranging from systemic/multisystem inflammation and worsened disease severity to logistical barriers to treatment caused by COVID-19. Further research is needed to determine causality of these findings.

Increased time to surgery and worse perioperative outcome in benign brain tumor patients with COVID-19.

BACKGROUND: The COVID-19 pandemic caused significant disruptions to healthcare systems around the world, due to both high resource utilization and concern for disease spread. Delays in non-emergent surgeries have also affected chronic disease management, including that of benign brain tumors such as meningiomas and pituitary adenomas. To evaluate the effect of COVID-19 infection on benign brain tumor resection rates and subsequent perioperative and inpatient outcomes, this study utilized the 2020 National Inpatient Sample (NIS) to investigate rates of surgical resection, time to surgery, and mortality among benign brain tumor patients with and without COVID-19. METHODS: Patient data from April 2020 to December 2020 was extracted from the NIS. Confirmed COVID-19 diagnosis was identified using the ICD-10 diagnosis code U07.1. Patients with benign neoplasms of the cerebral meninges, cranial nerves, pituitary gland, craniopharyngeal duct, and brain were included in the study. Patient socio-demographics, hospital characteristics, and clinical comorbidities were obtained. Outcome variables included rates of surgical resection, time to surgery, in-hospital mortality, length of stay, and discharge disposition. RESULTS: The study analysis consisted of 13,053 patients with benign intracranial neoplasms who met inclusion criteria; 597 (4.6%) patients were COVID-19 positive. Patients with COVID-19 were more likely to be older and male than COVID-19 negative patients. Patients with COVID-19 had increased overall likelihood of mortality (OR 2.36, 95% CI 1.72-3.25, p < 0.0001). Even when controlling for sociodemographic/hospital factors and comorbidities, COVID-19 positive patients had a significantly longer time to surgery (8.7 days vs. 0.9 days, p < 0.0001) than COVID negative patients, and were associated with a decreased likelihood of undergoing surgery on index admission overall (OR 0.17, 95% CI 0.10-0.29, p < 0.0001). CONCLUSIONS: As expected, COVID-19 infection was associated with worse inpatient outcomes in effectively all measured categories, including longer time to surgery, decreased likelihood of receiving surgery on index admission, and increased likelihood of in-hospital mortality. These findings emphasize the effect that COVID-19 has on other aspects of patient care and highlight the importance of appropriate avenues of care for patients who are COVID-19 positive. Although the COVID-19 pandemic is no longer a public health emergency, understanding the pandemic's impact on outcome for these patients is essential in efficient triage and optimizing treatment for these patients in the future. Further study is needed to elucidate causal relationships on the outcomes of benign brain tumor patients.

Coronavirus disease-19 is associated with decreased treatment access and worsened outcomes in malignant brain tumor patients.

Background: The global coronavirus disease-19 (COVID-19) pandemic has resulted in procedural delays around the world; however, timely and aggressive surgical resection for malignant brain tumor patients is essential for outcome optimization. To investigate the association between COVID-19 and outcomes of these patients, we queried the 2020 National Inpatient Sample (NIS) for differences in rates of surgical resection, time to surgery, mortality, and discharge disposition between patients with and without confirmed COVID-19 infection. Methods: Patient data were taken from the NIS from April 2020 to December 2020. COVID-19 diagnosis was determined with the International Classification of Diseases, Tenth Revision, Clinical Modification code U07.1. Results: A total of 30,671 malignant brain tumor patients met inclusion criteria and 738 (2.4%) patients had a confirmed COVID-19 diagnosis. COVID-19-positive patients had lower likelihood of receiving surgery (Odds ratio [OR] 0.43, 95% confidence interval [CI] 0.29-0.63, P < 0.0001), increased likelihood of mortality (OR 2.18, 95% CI 1.78-2.66, P < 0.0001), and increased likelihood of non-routine discharge (OR 1.25, 95% CI 1.13-1.39, P < 0.0001). Notably, COVID patients receiving surgery were not associated with surgical delay (P = 0.17). Conclusion: COVID-19 infection was associated with worse patient outcome in malignant brain tumor patients, including decreased likelihood of receiving surgery, increased likelihood of mortality, and increased likelihood of non-routine discharge. Our study highlights the need to balance the risks and benefits of delaying surgery for malignant brain tumor patients with COVID-19. Although the COVID-19 pandemic is no longer a public health emergency, understanding the pandemic's impact on outcome provides important insight in effective triage for these patients in the situations where resources are limited.

GPT-4 Artificial Intelligence Model Outperforms ChatGPT, Medical Students, and Neurosurgery Residents on Neurosurgery Written Board-Like Questions.

BACKGROUND: Artificial intelligence (AI) and machine learning have transformed health care with applications in various specialized fields. Neurosurgery can benefit from artificial intelligence in surgical planning, predicting patient outcomes, and analyzing neuroimaging data. GPT-4, an updated language model with additional training parameters, has exhibited exceptional performance on standardized exams. This study examines GPT-4's competence on neurosurgical board-style questions, comparing its performance with medical students and residents, to explore its potential in medical education and clinical decision-making. METHODS: GPT-4's performance was examined on 643 Congress of Neurological Surgeons Self-Assessment Neurosurgery Exam (SANS) board-style questions from various neurosurgery subspecialties. Of these, 477 were text-based and 166 contained images. GPT-4 refused to answer 52 questions that contained no text. The remaining 591 questions were inputted into GPT-4, and its performance was evaluated based on first-time responses. Raw scores were analyzed across subspecialties and question types, and then compared to previous findings on Chat Generative pre-trained transformer performance against SANS users, medical students, and neurosurgery residents. RESULTS: GPT-4 attempted 91.9% of Congress of Neurological Surgeons SANS questions and achieved 76.6% accuracy. The model's accuracy increased to 79.0% for text-only questions. GPT-4 outperformed Chat Generative pre-trained transformer (P < 0.001) and scored highest in pain/peripheral nerve (84%) and lowest in spine (73%) categories. It exceeded the performance of medical students (26.3%), neurosurgery residents (61.5%), and the national average of SANS users (69.3%) across all categories. CONCLUSIONS: GPT-4 significantly outperformed medical students, neurosurgery residents, and the national average of SANS users. The mode's accuracy suggests potential applications in educational settings and clinical decision-making, enhancing provider efficiency, and improving patient care.

Roadmap for Successful Research Training in Neurosurgery.

A benchmark of success for the neurosurgeon-scientist includes obtaining individual research funding from the National Institutes of Health. Successful roadmaps to this goal highlight individual commitment and resiliency, innovative research goals, intentional mentoring, protected research time, and financial support. Neurosurgery residents must carefully plan their training career to surmount obstacles such as long clinical training period, gaps in research productivity during clinical training, and limited protected time for research to ensure successful transition to independent research careers. To maximize potential for success as a neurosurgeon-scientist, individuals should have strong research experience on entering residency, choose residency programs that enthusiastically commit to research success among its residents, choose research mentors who will guide them expertly toward a research career, and become well-prepared to apply for research funding during residency. Moreover, individuals who wish to become leaders as neurosurgeon-researchers should seek environments that provide exposure to the widest range of experiences, perspectives, and thinking about medical and research problems.

Roadmap for Development of a Strong, Diverse Research Workforce in Neurosurgery.

A benchmark of success for the neurosurgeon-scientist includes obtaining individual research funding from the National Institutes of Health. Successful roadmaps to this goal highlight diversity, individual commitment and resiliency, innovative research goals, intentional mentoring, protected research time, and financial support. We must equip neurosurgery residents to surmount obstacles such as long periods of training, gaps in research productivity, and limited protected time for research to ensure successful transition to independent research careers. Strong individual, departmental, and national commitment to scientific development of a diverse cohort of residents and junior faculty will increase the number and diversity of National Institutes of Health-funded neurosurgeon-scientists.

Magnetic resonance imaging of white matter response to diesel exhaust particles.

Air pollution is associated with risks of dementia and accelerated cognitive decline. Rodent air pollution models have shown white matter vulnerability. This study uses diffusion tensor imaging (DTI) to quantify changes to white matter microstructure and tractography in multiple myelinated regions after exposure to diesel exhaust particulate (DEP). Adult C57BL/6 male mice were exposed to re-aerosolized DEP (NIST SRM 2975) at a concentration of 100 ug/m3 for 200 hours. Ex-vivo MRI analysis and fractional anisotropy (FA)-aided white matter tractography were conducted to study the effect of DEP exposure on the brain white matter tracts. Immunohistochemistry was used to assess myelin and axonal structure. DEP exposure for 8 weeks altered myelin composition in multiple regions. Diffusion tensor imaging (DTI) showed decreased FA in the corpus callosum (30%), external capsule (15%), internal capsule (15%), and cingulum (31 %). Separate immunohistochemistry analyses confirmed prior findings. Myelin basic protein (MBP) was decreased (corpus callosum: 28%, external capsule: 29%), and degraded MPB increased (corpus callosum: 32%, external capsule: 53%) in the DEP group. White matter is highly susceptible to chronic DEP exposure. This study demonstrates the utility of DTI as a neuroanatomical tool in the context of air pollution and white matter myelin vulnerability.