Description of the local hemodynamic environment in intracranial aneurysm wall subdivisions.

Intracranial aneurysms (IAs) pose severe health risks influenced by hemodynamics. This study focuses on the intricate characterization of hemodynamic conditions within the IA walls and their influence on bleb development, aiming to enhance understanding of aneurysm stability and the risk of rupture. The methods emphasized utilizing a comprehensive dataset of 359 IAs and 213 IA blebs from 268 patients to reconstruct patient-specific vascular models, analyzing blood flow using finite element methods to solve the unsteady Navier-Stokes equations, the segmentation of aneurysm wall subregions and the hemodynamic metrics wall shear stress (WSS), its metrics, and the critical points in WSS fields were computed and analyzed across different aneurysm subregions defined by saccular, streamwise, and topographical divisions. The results revealed significant variations in these metrics, correlating distinct hemodynamic environments with wall features on the aneurysm walls, such as bleb formation. Critical findings indicated that regions with low WSS and high OSI, particularly in the body and central regions of aneurysms, are prone to conditions that promote bleb formation. Conversely, areas exposed to high WSS and positive divergence, like the aneurysm neck, inflow, and outflow regions, exhibited a different but substantial risk profile for bleb development, influenced by flow impingements and convergences. These insights highlight the complexity of aneurysm behavior, suggesting that both high and low-shear environments can contribute to aneurysm pathology through distinct mechanisms.

Addressing the Evidence Gap in Aneurysmal Subarachnoid Hemorrhage: The Need for a Pragmatic Randomized Trial Platform.

Aneurysmal subarachnoid hemorrhage (aSAH) occurs less often than other stroke types but affects younger patients, imposing a disproportionately high burden of long-term disability. Although management advances have improved outcomes over time, relatively few aSAH treatments have been tested in randomized clinical trials (RCTs). One lesson learned from COVID-19 is that trial platforms can facilitate the efficient execution of multicenter RCTs even in complex diseases during challenging conditions. An aSAH trial platform with standardized eligibility criteria, randomization procedures, and end point definitions would enable the study of multiple targeted interventions in a perpetual manner, with treatments entering and leaving the platform based on predefined decision algorithms. An umbrella institutional review board protocol and clinical trial agreement would allow individual arms to be efficiently added as amendments rather than stand-alone protocols. Standardized case report forms using the National Institutes of Health/National Institute of Neurological Disorders and Stroke common data elements and general protocol standardization across arms would create synergies for data management and monitoring. A Bayesian analysis framework would emphasize frequent interim looks to enable early termination of trial arms for futility, common controls, borrowing of information across arms, and adaptive designs. A protocol development committee would assist investigators and encourage pragmatic designs to maximize generalizability, reduce site burden, and execute trials efficiently and cost-effectively. Despite decades of steady clinical progress in the management of aSAH, poor patient outcomes remain common, and despite the increasing availability of RCT data in other fields, it remains difficult to perform RCTs to guide more effective care for aSAH. The development of a platform for pragmatic RCTs in aSAH would help close the evidence gap between aSAH and other stroke types and improve outcomes for this important disease with its disproportionate public health burden.

Neuropsychological Test Performance Differentiates Subgroups of Individuals With Adult Moyamoya Disease: A Cross-Sectional Clinical Study.

BACKGROUND AND OBJECTIVES: Moyamoya disease (MMD) is a rare noninflammatory disorder involving progressive intracranial vasculopathy and impaired cerebral blood flow in the anterior circulation, resulting in stroke and cognitive impairment. We aimed to characterize cognitive impairment and the possible predictive value of sociodemographic and clinical characteristics of adults with MMD. METHODS: This cross-sectional study examined neurocognitive performance in a group of 42 consecutive adult patients (mean age = 40.52 years; 69% female) referred for a presurgical neuropsychological evaluation. Neuropsychological functioning was assessed with a comprehensive battery, and cognitive dysfunction was defined as 1.5 SDs below the mean. Neurocognitive performance correlated with clinical/demographic characteristics and disease markers. RESULTS: Most patients (91%) had a history of stroke, and 45% had cognitive deficits, most notably on measures of attention/speed (48%), executive functioning (47%), visuoconstruction (41%), and memory (31%-54%). Only higher educational attainment and poor collateral blood flow in the right hemisphere differentiated cognitively impaired (n = 19) and intact groups (n = 23), and MMD-related characteristics (eg, disease duration, stroke history) did not differentiate the 2 groups. CONCLUSION: Consistent with previous work, frontal-subcortical cognitive deficits (eg, deficits in mental speed, attention, executive functioning) were found in nearly half of patients with MMD and better cognitive performance was associated with factors related to cognitive reserve. Angiographic metrics of disease burden (eg, Suzuki rating, collateral flow) and hemodynamic reserve were not consistently associated with poorer cognitive outcomes, suggesting that cognition is a crucial independent factor to assess in MMD and has relevance for treatment planning and functional status.

Distribution of rupture sites and blebs on intracranial aneurysm walls suggests distinct rupture patterns in ACom and MCA aneurysms.

The mechanisms behind intracranial aneurysm formation and rupture are not fully understood, with factors such as location, patient demographics, and hemodynamics playing a role. Additionally, the significance of anatomical features like blebs in ruptures is debated. This highlights the necessity for comprehensive research that combines patient-specific risk factors with a detailed analysis of local hemodynamic characteristics at bleb and rupture sites. Our study analyzed 359 intracranial aneurysms from 268 patients, reconstructing patient-specific models for hemodynamic simulations based on 3D rotational angiographic images and intraoperative videos. We identified aneurysm subregions and delineated rupture sites, characterizing blebs and their regional overlap, employing statistical comparisons across demographics, and other risk factors. This work identifies patterns in aneurysm rupture sites, predominantly at the dome, with variations across patient demographics. Hypertensive and anterior communicating artery (ACom) aneurysms showed specific rupture patterns and bleb associations, indicating two pathways: high-flow in ACom with thin blebs at impingement sites and low-flow, oscillatory conditions in middle cerebral artery (MCA) aneurysms fostering thick blebs. Bleb characteristics varied with gender, age, and smoking, linking rupture risks to hemodynamic factors and patient profiles. These insights enhance understanding of the hemodynamic mechanisms leading to rupture events. This analysis elucidates the role of localized hemodynamics in intracranial aneurysm rupture, challenging the emphasis on location by revealing how flow variations influence stability and risk. We identify two pathways to wall failure-high-flow and low-flow conditions-highlighting the complexity of aneurysm behavior. Additionally, this research advances our knowledge of how inherent patient-specific characteristics impact these processes, which need further investigation.

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.

Predictors of angiographic resolution in patients with presumed reversible cerebral vasoconstriction syndrome.

INTRODUCTION: Reversible cerebral vasoconstriction syndrome is a complex neurovascular syndrome that presents with varying neurological deficits as well as segmental vasoconstriction of the small and medium cerebral arteries. There is limited literature on pathologies that mimic reversible cerebral vasoconstriction syndrome, so this study aims to understand what factors may impact the angiographic confirmation of reversible cerebral vasoconstriction syndrome on follow-up and play a role in establishing the diagnosis. METHODS: The Clinical Research Data Warehouse at this institution was employed to search the medical records for patients with diagnosis and treatment of reversible cerebral vasoconstriction syndrome between January 2010 and May 2021. After screening, 32 patients met the inclusion criteria for a presumed diagnosis of reversible cerebral vasoconstriction syndrome with both angiography on presentation and at three-month follow-up after treatment. Patients were divided into two categories: those with complete angiographic resolution, versus partial or no improvement on follow-up. Clinical and radiographic data were analyzed. RESULTS: Patients who had partial or no resolution were more likely to have a history of hypertension (p = 0.001), higher systolic blood pressure on admission (p = 0.047), and present with a recurrent thunderclap headache (p = 0.038). Binary logistic regression selected for hypertension (odds ratio [OR] 18.35 [95% CI, 1.37-245.1]) as predictive of not having reversible cerebral vasoconstriction syndrome, as can be seen by partial or no resolution on follow-up angiography (p = 0.028). CONCLUSION: Complete resolution on follow-up angiography is a distinguishing factor of reversible cerebral vasoconstriction syndrome. Our analysis revealed that a history of hypertension is the most significant predictor of confirming that a patient may not have reversible cerebral vasoconstriction syndrome. This is due, in part, to increased atherosclerotic or hypertensive cerebral arterial changes, which can mimic reversible cerebral vasoconstriction syndrome and present as partial or no resolution on angiography.

Dural arteriovenous fistulas are not observed to convert to a higher grade after partial embolization.

OBJECTIVE: Borden-Shucart type I dural arteriovenous fistulas (dAVFs) lack cortical venous drainage and occasionally necessitate intervention depending on patient symptoms. Conversion is the rare transformation of a low-grade dAVF to a higher grade. Factors associated with increased risk of dAVF conversion to a higher grade are poorly understood. The authors hypothesized that partial treatment of type I dAVFs is an independent risk factor for conversion. METHODS: The multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research database was used to perform a retrospective analysis of all patients with type I dAVFs. RESULTS: Three hundred fifty-eight (33.2%) of 1077 patients had type I dAVFs. Of those 358 patients, 206 received endovascular treatment and 131 were not treated. Two (2.2%) of 91 patients receiving partial endovascular treatment for a low-grade dAVF experienced conversion to a higher grade, 2 (1.5%) of 131 who were not treated experienced conversion, and none (0%) of 115 patients who received complete endovascular treatment experienced dAVF conversion. The majority of converted dAVFs localized to the transverse-sigmoid sinus and all received embolization as part of their treatment. CONCLUSIONS: Partial treatment of type I dAVFs does not appear to be significantly associated with conversion to a higher grade.

Comapping Cellular Content and Extracellular Matrix with Hemodynamics in Intact Arterial Tissues Using Scanning Immunofluorescent Multiphoton Microscopy.

Deviation of blood flow from an optimal range is known to be associated with the initiation and progression of vascular pathologies. Important open questions remain about how the abnormal flow drives specific wall changes in pathologies such as cerebral aneurysms where the flow is highly heterogeneous and complex. This knowledge gap precludes the clinical use of readily available flow data to predict outcomes and improve treatment of these diseases. As both flow and the pathological wall changes are spatially heterogeneous, a crucial requirement for progress in this area is a methodology for acquiring and comapping local vascular wall biology data with local hemodynamic data. Here, we developed an imaging pipeline to address this pressing need. A protocol that employs scanning multiphoton microscopy was developed to obtain three-dimensional (3D) datasets for smooth muscle actin, collagen, and elastin in intact vascular specimens. A cluster analysis was introduced to objectively categorize the smooth muscle cells (SMC) across the vascular specimen based on SMC actin density. Finally, direct quantitative comparison of local flow and wall biology in 3D intact specimens was achieved by comapping both heterogeneous SMC data and wall thickness to patient-specific hemodynamic results.

Future of Endovascular and Surgical Treatments of Atherosclerotic Intracranial Stenosis.

Intracranial atherosclerotic disease and resultant intracranial stenosis is a global leading cause of stroke, and poses an ongoing treatment challenge. Among patients with intracranial stenosis, those with hemodynamic compromise are at high risk for recurrent stroke despite medical therapy and risk factor modification. Revascularization of the hypoperfused territory is the most plausible treatment strategy for these high-risk patients, yet surgical and endovascular therapies have not yet shown to be sufficiently safe and effective in randomized controlled trials. Advances in diagnostic and therapeutic technologies have led to a resurgence of interest in surgical and endovascular treatment strategies, with a growing body of evidence to support their further evaluation in the treatment of select patient populations. This review outlines the current and emerging endovascular and surgical treatments and highlights promising future management strategies.

Emergent Large Vessel Occlusion due to Intracranial Stenosis: Identification, Management, Challenges, and Future Directions.

This comprehensive literature review focuses on acute stroke related to intracranial atherosclerotic stenosis (ICAS), with an emphasis on ICAS-large vessel occlusion. ICAS is the leading cause of stroke globally, with high recurrence risk, especially in Asian, Black, and Hispanic populations. Various risk factors, including hypertension, diabetes, hyperlipidemia, smoking, and advanced age lead to ICAS, which in turn results in stroke through different mechanisms. Recurrent stroke risk in patients with ICAS with hemodynamic failure is particularly high, even with aggressive medical management. Developments in advanced imaging have improved our understanding of ICAS and ability to identify high-risk patients who could benefit from intervention. Herein, we focus on current management strategies for ICAS-large vessel occlusion discussed, including the use of perfusion imaging, endovascular therapy, and stenting. In addition, we focus on strategies that aim at identifying subjects at higher risk for early recurrent risk who could benefit from early endovascular intervention The review underscores the need for further research to optimize ICAS-large vessel occlusion treatment strategies, a traditionally understudied topic.

Evaluating outcome associations with race after mechanical thrombectomy: an analysis of the NVQI-QOD acute ischemic stroke registry.

BACKGROUND: Mechanical thrombectomy has become the standard of care for acute ischemic stroke due to large vessel occlusions. Racial differences in outcomes after mechanical thrombectomy for acute ischemic stroke have not been extensively studied. We evaluate the real-world evidence for differences between races in the outcomes of thrombectomy for large vessel occlusions using the NeuroVascular Quality Initiative-Quality Outcomes Database (NVQI-QOD). METHODS: Data from the NVQI-QOD acute ischemic stroke registry were analyzed and compared for racial differences in outcomes after mechanical thrombectomy in 4507 patients from 28 US centers (17 states) between January 2014 and April 2021. Race was dichotomized into non-Hispanic White (NHW, n=3649) and non-Hispanic Black (NHB, n=858). We performed 1:1 propensity score matching resulting in a subsample of matched groups (n=761 each for NHB and NHW) to compare study endpoints using Welch's two-sided t-tests and Χ2 test for continuous and categorical outcomes, respectively. RESULTS: Prior to matching, NHW and NHB patients significantly differed in age, comorbidities, medication use, smoking status, and presenting stroke severity. No significant difference in functional outcomes or mortality, at discharge or follow-up, were revealed. NHB patients had higher average postprocedure length of stay than NHW patients, which persisted following matching (11.2 vs 9.1 days, P=0.004). CONCLUSION: Evidence from the NVQI-QOD acute ischemic stroke registry showed that outcome metrics, such as modified Rankin Scale score and mortality, did not differ significantly between racial groups; however, disparity between NHW and NHB patients in postprocedure length of stay following mechanical thrombectomy was revealed.

Co-mapping Cellular Content and Extracellular Matrix with Hemodynamics in Intact Arterial Tissues Using Scanning Immunofluorescent Multiphoton Microscopy.

Deviation of blood flow from an optimal range is known to be associated with the initiation and progression of vascular pathologies. Important open questions remain about how the abnormal flow drives specific wall changes in pathologies such as cerebral aneurysms where the flow is highly heterogeneous and complex. This knowledge gap precludes the clinical use of readily available flow data to predict outcomes and improve treatment of these diseases. As both flow and the pathological wall changes are spatially heterogeneous, a crucial requirement for progress in this area is a methodology for co-mapping local data from vascular wall biology with local hemodynamic data. In this study, we developed an imaging pipeline to address this pressing need. A protocol that employs scanning multiphoton microscopy was designed to obtain 3D data sets for smooth muscle actin, collagen and elastin in intact vascular specimens. A cluster analysis was developed to objectively categorize the smooth muscle cells (SMC) across the vascular specimen based on SMC density. In the final step in this pipeline, the location specific categorization of SMC, along with wall thickness was co-mapped with patient specific hemodynamic results, enabling direct quantitative comparison of local flow and wall biology in 3D intact specimens.

The VEBAS score: a practical scoring system for intracranial dural arteriovenous fistula obliteration.

BACKGROUND: Tools predicting intracranial dural arteriovenous fistulas (dAVFs) treatment outcomes remain scarce. This study aimed to use a multicenter database comprising more than 1000 dAVFs to develop a practical scoring system that predicts treatment outcomes. METHODS: Patients with angiographically confirmed dAVFs who underwent treatment within the Consortium for Dural Arteriovenous Fistula Outcomes Research-participating institutions were retrospectively reviewed. A subset comprising 80% of patients was randomly selected as training dataset, and the remaining 20% was used for validation. Univariable predictors of complete dAVF obliteration were entered into a stepwise multivariable regression model. The components of the proposed score (VEBAS) were weighted based on their ORs. Model performance was assessed using receiver operating curves (ROC) and areas under the ROC. RESULTS: A total of 880 dAVF patients were included. Venous stenosis (presence vs absence), elderly age (<75 vs ≥75 years), Borden classification (I vs II-III), arterial feeders (single vs multiple), and past cranial surgery (presence vs absence) were independent predictors of obliteration and used to derive the VEBAS score. A significant increase in the likelihood of complete obliteration (OR=1.37 (1.27-1.48)) with each additional point in the overall patient score (range 0-12) was demonstrated. Within the validation dataset, the predicted probability of complete dAVF obliteration increased from 0% with a 0-3 score to 72-89% for patients scoring ≥8. CONCLUSION: The VEBAS score is a practical grading system that can guide patient counseling when considering dAVF intervention by predicting the likelihood of treatment success, with higher scores portending a greater likelihood of complete obliteration.

Dural Arteriovenous Fistulas With Cognitive Impairment: Angiographic Characteristics and Treatment Outcomes.

BACKGROUND AND OBJECTIVES: Anecdotal cases of rapidly progressing dementia in patients with dural arteriovenous fistulas (dAVFs) have been reported in small series. However, large series have not characterized these dAVFs. We conducted an analysis of the largest cohort of dAVFs presenting with cognitive impairment (dAVFs-CI), aiming to provide a detailed characterization of this subset of dAVFs. METHODS: Patients with dAVFs-CI were analyzed from the CONDOR Consortium, a multicenter repository comprising 1077 dAVFs. A propensity score matching analysis was conducted to compare dAVFs-CI with Borden type II and type III dAVFs without cognitive impairment (controls). Logistic regression was used to identify angiographic characteristics specific to dAVFs-CI. Furthermore, post-treatment outcomes were analyzed. RESULTS: A total of 60 patients with dAVFs-CI and 60 control dAVFs were included. Outflow obstruction leading to venous hypertension was observed in all dAVFs-CI. Sinus stenosis was significantly associated with dAVFs-CI (OR 2.85, 95% CI: 1.16-7.55, P = .027). dAVFs-CI were more likely to have a higher number of arterial feeders (OR 1.56, 95% CI 1.22-2.05, P < .001) and draining veins (OR 2.05, 95% CI 1.05-4.46, P = .004). Venous ectasia increased the risk of dAVFs-CI (OR 2.38, 95% CI 1.13-5.11, P = .024). A trend toward achieving asymptomatic status at follow-up was observed in patients with successful closure of dAVFs (OR 2.86, 95% CI 0.85-9.56, P = .09). CONCLUSION: Venous hypertension is a key angiographic feature of dAVFs-CI. Moreover, these fistulas present at a mean age of 58 years-old, and exhibit a complex angioarchitecture characterized by an increased number of arteriovenous connections and stenosed sinuses. The presence of venous ectasia further exacerbates the impaired drainage and contributes to the development of dAVFs-CI. Notably, in certain cases, closure of the dAVF has the potential to reverse symptoms.

Outcomes Associated With Intracranial Aneurysm Treatments Reported as Safe, Effective, or Durable: A Systematic Review and Meta-Analysis.

Importance: Testing new medical devices or procedures in terms of safety, effectiveness, and durability should follow the strictest methodological rigor before implementation. Objectives: To review and analyze studies investigating devices and procedures used in intracranial aneurysm (IA) treatment for methods and completeness of reporting and to compare the results of studies with positive, uncertain, and negative conclusions. Data Sources: Embase, MEDLINE, Web of Science, and The Cochrane Central Register of Clinical Trials were searched for studies on IA treatment published between January 1, 1995, and the October 1, 2022. Grey literature was retrieved from Google Scholar. Study Selection: All studies making any kind of claims of safety, effectiveness, or durability in the field of IA treatment were included. Data Extraction and Synthesis: Using a predefined data dictionary and analysis plan, variables ranging from patient and aneurysm characteristics to the results of treatment were extracted, as were details pertaining to study methods and completeness of reporting. Extraction was performed by 10 independent reviewers. A blinded academic neuro-linguist without involvement in IA research evaluated the conclusion of each study as either positive, uncertain, or negative. The study followed Preferring Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Main Outcomes and Measures: The incidence of domain-specific outcomes between studies with positive, uncertain, or negative conclusions regarding safety, effectiveness, or durability were compared. The number of studies that provided a definition of safety, effectiveness, or durability and the incidence of incomplete reporting of domain-specific outcomes were evaluated. Results: Overall, 12 954 studies were screened, and 1356 studies were included, comprising a total of 410 993 treated patients. There was no difference in the proportion of patients with poor outcome or in-hospital mortality between studies claiming a technique was safe, uncertain, or not safe. Similarly, there was no difference in the proportion of IAs completely occluded at last follow-up between studies claiming a technique was effective, uncertain, or noneffective. Less than 2% of studies provided any definition of safety, effectiveness, or durability, and only 1 of the 1356 studies provided a threshold under which the technique would be considered unsafe. Incomplete reporting was found in 546 reports (40%). Conclusions and Relevance: In this systematic review and meta-analysis of IA treatment literature, studies claiming safety, effectiveness, or durability of IA treatment had methodological flaws and incomplete reporting of relevant outcomes supporting these claims.

Adult Moyamoya Disease and Syndrome: Current Perspectives and Future Directions: A Scientific Statement From the American Heart Association/American Stroke Association.

Adult moyamoya disease and syndrome are rare disorders with significant morbidity and mortality. A writing group of experts was selected to conduct a literature search, summarize the current knowledge on the topic, and provide a road map for future investigation. The document presents an update in the definitions of moyamoya disease and syndrome, modern methods for diagnosis, and updated information on pathophysiology, epidemiology, and both medical and surgical treatment. Despite recent advancements, there are still many unresolved questions about moyamoya disease and syndrome, including lack of unified diagnostic criteria, reliable biomarkers, better understanding of the underlying pathophysiology, and stronger evidence for treatment guidelines. To advance progress in this area, it is crucial to acknowledge the limitations and weaknesses of current studies and explore new approaches, which are outlined in this scientific statement for future research strategies.

Extracranial-Intracranial Bypass and Risk of Stroke and Death in Patients With Symptomatic Artery Occlusion: The CMOSS Randomized Clinical Trial.

Importance: Prior trials of extracranial-intracranial (EC-IC) bypass surgery showed no benefit for stroke prevention in patients with atherosclerotic occlusion of the internal carotid artery (ICA) or middle cerebral artery (MCA), but there have been subsequent improvements in surgical techniques and patient selection. Objective: To evaluate EC-IC bypass surgery in symptomatic patients with atherosclerotic occlusion of the ICA or MCA, using refined patient and operator selection. Design, Setting, and Participants: This was a randomized, open-label, outcome assessor-blinded trial conducted at 13 centers in China. A total of 324 patients with ICA or MCA occlusion with transient ischemic attack or nondisabling ischemic stroke attributed to hemodynamic insufficiency based on computed tomography perfusion imaging were recruited between June 2013 and March 2018 (final follow-up: March 18, 2020). Interventions: EC-IC bypass surgery plus medical therapy (surgical group; n = 161) or medical therapy alone (medical group; n = 163). Medical therapy included antiplatelet therapy and stroke risk factor control. Main Outcomes and Measures: The primary outcome was a composite of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years after randomization. There were 9 secondary outcomes, including any stroke or death within 2 years and fatal stroke within 2 years. Results: Among 330 patients who were enrolled, 324 patients were confirmed eligible (median age, 52.7 years; 257 men [79.3%]) and 309 (95.4%) completed the trial. For the surgical group vs medical group, no significant difference was found for the composite primary outcome (8.6% [13/151] vs 12.3% [19/155]; incidence difference, -3.6% [95% CI, -10.1% to 2.9%]; hazard ratio [HR], 0.71 [95% CI, 0.33-1.54]; P = .39). The 30-day risk of stroke or death was 6.2% (10/161) in the surgical group and 1.8% (3/163) in the medical group, and the risk of ipsilateral ischemic stroke beyond 30 days through 2 years was 2.0% (3/151) and 10.3% (16/155), respectively. Of the 9 prespecified secondary end points, none showed a significant difference including any stroke or death within 2 years (9.9% [15/152] vs 15.3% [24/157]; incidence difference, -5.4% [95% CI, -12.5% to 1.7%]; HR, 0.69 [95% CI, 0.34-1.39]; P = .30) and fatal stroke within 2 years (2.0% [3/150] vs 0% [0/153]; incidence difference, 1.9% [95% CI, -0.2% to 4.0%]; P = .08). Conclusions and Relevance: Among patients with symptomatic ICA or MCA occlusion and hemodynamic insufficiency, the addition of bypass surgery to medical therapy did not significantly change the risk of the composite outcome of stroke or death within 30 days or ipsilateral ischemic stroke beyond 30 days through 2 years. Trial Registration: ClinicalTrials.gov Identifier: NCT01758614.

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.

Hemodynamic outcomes of stenting for vertebrobasilar insufficiency in patients with a low flow state.

INTRODUCTION: The Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study determined patients with low flow in their vertebrobasilar (VB) system are at increased risk of recurrent stroke. Endovascular interventions such as angioplasty and stenting are reserved for patients with refractory symptoms; however, few series to date have demonstrated either hemodynamic or clinical outcomes in this high-risk patient group. We present our combined institutional series of patients with symptomatic VB atherosclerotic disease and low-flow state who underwent angioplasty and stenting. METHODS: Retrospective chart review of patients undergoing angioplasty and stenting for symptomatic VB atherosclerotic disease at two institutions was performed. Clinical and radiographical outcomes were collected including flow rates using quantitative MRA (QMRA) pre- and post-stenting. RESULTS: Seventeen patients underwent angioplasty and stenting for symptomatic VB atherosclerotic disease and met VERiTAS low-flow state criteria. There were four cases (23.5%) of periprocedural stroke, two of which were minor and transient. The stent was placed intracranially in 82.4% of patients. Basilar and bilateral posterior cerebral artery (PCA) flows significantly improved post-stenting (p < 0.05) and normalized based upon VERiTAS criteria in all patients. Fourteen patients had delayed QMRA at mean follow-up 20 months demonstrating appropriate patency and flow post-stenting. Two patients (10%) had recurrent stroke, one from medication nonadherence and in-stent thrombosis, and the other from a procedural dissection that subsequently became symptomatic. CONCLUSIONS: Our series demonstrates angioplasty and stenting significantly improve intracranial flow over long-term. Angioplasty and stenting may improve the natural history of low-flow VB atherosclerotic disease.