The differential proteomic response to ischemic stroke in appalachian subjects treated with mechanical thrombectomy.

INTRODUCTION: The Appalachia region of North America is known to have significant health disparities, specifically, worse risk factors and outcomes for stroke. Appalachians are more likely to have comorbidities related to stroke, such as diabetes, obesity, and tobacco use, and are often less likely to have stroke interventions, such as mechanical thrombectomy (MT), for emergent large vessel occlusion (ELVO). As our Comprehensive Stroke Center directly serves stroke subjects from both Appalachian and non-Appalachian areas, inflammatory proteomic biomarkers were identified associated with stroke outcomes specific to subjects residing in Appalachia. METHODS: There were 81 subjects that met inclusion criteria for this study. These subjects underwent MT for ELVO, and carotid arterial blood samples acquired at time of intervention were sent for proteomic analysis. Samples were processed in accordance with the Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC; clinicaltrials.gov; NCT03153683). Statistical analyses were utilized to examine whether relationships between protein expression and outcomes differed by Appalachian status for functional (NIH Stroke Scale; NIHSS and Modified Rankin Score; mRS), and cognitive outcomes (Montreal Cognitive Assessment; MoCA). RESULTS: No significant differences were found in demographic data or co-morbidities when comparing Appalachian to non-Appalachian subjects. However, time from stroke onset to treatment (last known normal) was significantly longer and edema volume significantly higher in patients from Appalachia. Further, when comparing Appalachian to non-Appalachian subjects, there were significant unadjusted differences in the NIHSS functional outcome. A comprehensive analysis of 184 proteins from Olink proteomic (92 Cardiometabolic and 92 Inflammation panels) showed that the association between protein expression outcomes significantly differed by Appalachian status for seven proteins for the NIHSS, two proteins for the MoCA, and three for the mRS. CONCLUSION: Our study utilizes an ELVO tissue bank and registry to investigate the intracranial/intravascular proteomic environment occurring at the time of thrombectomy. We found that patients presenting from Appalachian areas have different levels of proteomic expression at the time of MT when compared to patients presenting from non-Appalachian areas. These proteins differentially relate to stroke outcome and could be used as prognostic biomarkers, or as targets for novel therapies. The identification of a disparate proteomic response in Appalachian patients provides initial insight to the biological basis for health disparity. Nevertheless, further investigations through community-based studies are imperative to elucidate the underlying causes of this differential response.

Medical malpractice claims and state medical board complaints among United States neurointerventionalists.

BACKGROUND: Surgeons are at high risk for malpractice claims, which can significantly impact physician quality of life and risk of burnout. There are few published data reporting the incidence, outcomes, and repercussions of malpractice lawsuits on neurointerventionalists. METHODS: A survey of senior members of the United States Society of Neurointerventional Surgery (SNIS) was performed to study malpractice litigation and medical board complaints. RESULTS: In total, 173 responses were obtained. Of the total sample, 66 respondents (38.2%) reported being subject to a total of 84 malpractice claims during independent practice over the last 10 years, amounting to a malpractice claim annual incidence of 5.9% (84 cases per 1423 years of practice). The majority of claims involved either brain aneurysms (34.5%) or arteriovenous malformations (23.8%), with most alleging either intra-procedural (38.1%) or post-procedural (27.3%) complications. Only three of the 58 claims that had concluded ended in court settlements (5.2%). The majority (78.3%) of claims resulted in no consequences to physician practice. Fourteen respondents (8.1%) reported being subject to a total of 16 state medical board complaints over the previous decade, with most resulting in no significant repercussions. CONCLUSION: Malpractice claims are common among neurointerventionalists and often cause significant physician distress, yet most result in claims being dropped or no paid damages, and the majority conclude without practice repercussions for the named physicians.

Mechanical Thrombectomy Workshops Improve Procedural Knowledge and Skills Among Neurointerventional Teams in Low- to Middle-Income Countries.

BACKGROUND: While mechanical thrombectomy (MT) is proven to be lifesaving and disability sparing, there remains a disparity in its access in low- to middle-income countries. We hypothesized that team-based MT workshops would improve MT knowledge and skills. METHODS: We designed a 22-hour MT workshop, conducted as 2 identical events: in English (Jamaica, January 2022) and in Spanish (Dominican Republic, May 2022). The workshops included participating neurointerventional teams (practicing neurointerventionalists, neurointerventional nurses, and technicians) focused on acute stroke due to large vessel occlusion. The course faculty led didactic and hands-on components, covering topics from case selection and postoperative management to device technology and MT surgical techniques. Attendees were evaluated on stroke knowledge and MT skills before and after the course using a multiple choice exam and simulated procedures utilizing flow models under fluoroscopy, respectively. Press conferences for public education with invited government officials were included to raise stroke awareness. RESULTS: Twenty-two physicians and their teams from 8 countries across the Caribbean completed the didactic and hands-on training. Overall test scores (n=18) improved from 67% to 85% (P<0.002). Precourse and postcourse hands-on assessments demonstrated reduced time to completion from 36.5 to 21.1 minutes (P<0.001). All teams showed an improvement in measures of good MT techniques, with 39% improvement in complete reperfusion. Eight teams achieved a Thrombolysis in Cerebral Infarction score of 3 on pre-course versus 15 of 18 teams on post-course. There was a significant reduction in total potentially dangerous maneuvers (70% pre versus 20% post; P<0.002). Universally, the workshop was rated as satisfactory and likely to change practice in 93% Dominican Republic and 75% Jamaica. CONCLUSIONS: A team-based hands-on simulation approach to MT training is novel, feasible, and effective in improving procedural skills. Participants viewed these workshops as practice-changing and instrumental in creating a pathway for increasing access to MT in low- to middle-income countries.

Factors Affecting Selection of TraineE for Neurointervention (FASTEN).

BACKGROUND AND IMPORTANCE: Neurointervention is a very competitive specialty in the United States due to the limited number of training spots and the larger pool of applicants. The training standards are continuously updated to ensure solid training experiences. Factors affecting candidate(s) selection have not been fully established yet. Our study aims to investigate the factors influencing the selection process. METHODS: A 52-question survey was distributed to 93 program directors (PDs). The survey consisted of six categories: (a) Program characteristics, (b) Candidate demographics, (c) Educational credentials, (d) Personal traits, (e) Research and extracurricular activities, and (f) Overall final set of characteristics. The response rate was 59.1%. As per the programs' characteristics, neurosurgery was the most involved specialty in running the training programs (69%). Regarding demographics, the need for visa sponsorship held the greatest prominence with a mean score of 5.9 [standard deviation (SD) 2.9]. For the educational credentials, being a graduate from a neurosurgical residency and the institution where the candidate's residency training is/was scored the highest [5.4 (SD = 2.9), 5.4 (SD = 2.5), respectively]. Regarding the personal traits, assessment by faculty members achieved the highest score [8.9 (SD = 1)]. In terms of research/extracurricular activities, fluency in English had the highest score [7.2 (SD = 1.9)] followed by peer-reviewed/PubMed-indexed publications [6.4 (SD = 2.2)]. CONCLUSION: Our survey investigated the factors influencing the final decision when choosing the future neurointerventional trainee, including demographic, educational, research, and extracurricular activities, which might serve as valuable guidance for both applicants and programs to refine the selection process.

Beyond a team: The comprehensive interdisciplinary endocarditis program in the United States.

Although multidisciplinary teams have been shown to decrease in-hospital mortality for patient with infectious endocarditis, most studies have focused on the inpatient role of these teams, and are primarily based at European tertiary care centers. There is limited literature available on the optimal longitudinal care of this patient population. Here we outline our experience developing an interdisciplinary endocarditis program at the University of Kentucky, which cares for patients from their index hospitalization into the outpatient setting, while also coordinating transfers from regional hospitals and offering education to regional providers.

Now that the door is open: an update on ischemic stroke pharmacotherapeutics for the neurointerventionalist.

The last 10 years have seen a major shift in management of large vessel ischemic stroke with changes towards ever-expanding use of reperfusion therapies (intravenous thrombolysis and mechanical thrombectomy). These strategies 'open the door' to acute therapeutics for ischemic tissue, and we should investigate novel therapeutic approaches to enhance survival of recently reperfused brain. Key insights into new approaches have been provided through translational research models and preclinical paradigms, and through detailed research on ischemic mechanisms. Additional recent clinical trials offer exciting salvos into this new strategy of pairing reperfusion with neuroprotective therapy. This pairing strategy can be employed using drugs that have shown neuroprotective efficacy; neurointerventionalists can administer these during or immediately after reperfusion therapy. This represents a crucial moment when we emphasize reperfusion, and have the technological capability along with the clinical trial experience to lead the way in multiprong approaches to stroke treatment.

Fatal Oedipism: A Case Report and Literature Review.

PURPOSE: To describe a unique case of a fatal self-enucleation and review previously published cases. METHODS: The authors describe a unique case of a complete unilateral self-enucleation while under the influence of drugs, which resulted in severe intracranial hemorrhages, right internal carotid artery opacification, and death. A literature review was performed by searching articles published before January 2023 in the Pubmed/MEDLINE database using the keywords "auto-enucleation or self-enucleation." Cases of self-inflicted damage to the globe without severing any connections were excluded. RESULTS: A literature review identified a total of 54 articles and 75 patients who had self-enucleated at least one globe completely (84.0%). Their average age was 37 years and 50.7% were male. At the time of auto-enucleation, 64.0% of these patients had known psychiatric disorders, and 28.0% were found to be under the influence of illicit drugs or alcohol. Auto-enucleation resulted in intracranial complications in 26.7% of cases. There has been 1 prior case, which, like the authors' case, resulted in death due to intracranial complications. However, this occurred in a patient who partially enucleated one eye after a self-inflicted injury to the fellow eye. The current case is unique as these complications resulted from a complete unilateral auto-enucleation. CONCLUSIONS: The severity of this case's presentation and outcome highlights the importance of prompt neuroimaging and a thorough assessment. Prompt psychiatric assessment and treatment are also required.

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.

Inflammatory-associated proteomic predictors of cognitive outcome in subjects with ELVO treated by mechanical thrombectomy.

BACKGROUND: Emergent Large Vessel Occlusion (ELVO) stroke causes devastating vascular events which can lead to significant cognitive decline and dementia. In the subset of ELVO subjects treated with mechanical thrombectomy (MT) at our institution, we aimed to identify systemic and intracranial proteins predictive of cognitive function at time of discharge and at 90-days. These proteomic biomarkers may serve as prognostic indicators of recovery, as well as potential targets for novel/existing therapeutics to be delivered during the subacute stage of stroke recovery. METHODS: At the University of Kentucky Center for Advanced Translational Stroke Sciences, the BACTRAC tissue registry (clinicaltrials.gov; NCT03153683) of human biospecimens acquired during ELVO stroke by MT is utilized for research. Clinical data are collected on each enrolled subject who meets inclusion criteria. Blood samples obtained during thrombectomy were sent to Olink Proteomics for proteomic expression values. Montreal Cognitive Assessments (MoCA) were evaluated with categorical variables using ANOVA and t-tests, and continuous variables using Pearson correlations. RESULTS: There were n = 52 subjects with discharge MoCA scores and n = 28 subjects with 90-day MoCA scores. Several systemic and intracranial proteins were identified as having significant correlations to discharge MoCA scores as well as 90-day MoCA scores. Highlighted proteins included s-DPP4, CCL11, IGFBP3, DNER, NRP1, MCP1, and COMP. CONCLUSION: We set out to identify proteomic predictors and potential therapeutic targets related to cognitive outcomes in ELVO subjects undergoing MT. Here, we identify several proteins which predicted MoCA after MT, which may serve as therapeutic targets to lessen post-stroke cognitive decline.

Internal Carotid Artery Stenosis: A Surgical Mouse Model to Study Moyamoya Syndrome.

Moyamoya is a cerebrovascular condition that predisposes affected patients to stroke and is characterized as the progressive stenosis of the internal carotid artery (ICA) and compensatory development of collaterals at the base of the brain. Patients with moyamoya syndrome also present with comorbidities such as various autoimmune diseases and coagulopathies. We developed a surgical method using micro-coils to induce ICA-specific stenosis in mice, which induces moyamoya-like vasculopathies. An advantage of this surgical model of hypoperfusion is that it can be combined with other comorbid models to investigate pathologies associated with moyamoya syndrome.

Reverse Translation to Develop Post-stroke Therapeutic Interventions during Mechanical Thrombectomy: Lessons from the BACTRAC Trial.

The majority of strokes, approximately 87%, are ischemic in etiology with the remaining hemorrhagic in origin. Emergent large vessel occlusions (ELVOs) are a subtype of ischemic stroke accounting for approximately 30-40% of acute large vessel blockages. Treatment for ELVOs focuses on recanalization of the occluded vessel by time-sensitive administration of tissue plasminogen activator (tPA) or thrombus removal using mechanical thrombectomy. Although a great deal of time and resources have focused on translational stroke research, little progress has been made in the area of identifying additional new treatments for stroke. Translational limitations include difficulty simulating human comorbid conditions in animal models, as well as the temporal nature of stroke pathology. The Blood And Clot Thrombectomy Registry And Collaboration represents an ongoing tissue registry for thrombectomy patients and includes collection of intracranial arterial blood, systemic arterial blood, thrombi, as well as a series of clinical and radiographic data points for analysis. This chapter will explore the methodologies employed and results obtained from studying BACTRAC-derived human biological specimens and how they can inform translational experimental design in animal studies.

Society of NeuroInterventional Surgery: position statement on pregnancy and parental leave for physicians practicing neurointerventional surgery.

BACKGROUND: The aim of this article is to outline a position statement on pregnancy and parental leave for physicians practicing neurointerventional surgery. METHODS: We performed a structured literature review regarding parental leave policies in neurointerventional surgery and related fields. The recommendations resulted from discussion among the authors, and additional input from the Women in NeuroIntervention Committee, the full Society of NeuroInterventional Surgery (SNIS) Standards and Guidelines Committee, and the SNIS Board of Directors. RESULTS: Some aspects of workplace safety during pregnancy are regulated by the US Nuclear Regulatory Commission. Other aspects of the workplace and reasonable job accommodations are legally governed by the Family and Medical Leave Act of 1993, the Affordable Care Act of 2010 and the Fair Labor Standards Act of 1938, Americans with Disabilities Act of 1990, Title IX of the Education Amendments of 1972, Title VII of the Civil Rights Act of 1964 as well as rights and protections put forth by the Occupational Safety and Health Administration as part of the United States Department of Labor. Family friendly policies have been associated not only with improved job satisfaction but also with improved parental and infant outcomes. Secondary effects of such accommodations are to increase the number of women within the specialty. CONCLUSIONS: SNIS supports a physician's ambition to have a family as well as start, develop, and maintain a career in neurointerventional surgery. Legal and regulatory mandates and family friendly workplace policies should be considered when institutions and individual practitioners approach the issue of childbearing in the context of a career in neurointerventional surgery.

Cannabidiol's Multifactorial Mechanisms Has Therapeutic Potential for Aneurysmal Subarachnoid Hemorrhage: a Review.

Subarachnoid hemorrhage (SAH) is a major health burden that accounts for approximately 5% of all strokes. The most common cause of a non-traumatic SAH is the rupture of a cerebral aneurysm. The most common symptom associated with SAH is a headache, often described as "the worst headache of my life." Delayed cerebral ischemia (DCI) is a major factor associated with patient mortality following SAH and is often associated with SAH-induced cerebral vasospasm (CV). Cannabidiol (CBD) is emerging as a potential drug for many therapeutic purposes, including epilepsy, anxiety, and pain relief. We aim to review the potential use of CBD as a treatment option for post-SAH critically ill patients. Through a literature review, we evaluated the known pharmacology and physiological effects of CBD and correlated those with the pathophysiological outcomes associated with cerebral vasospasm following subarachnoid hemorrhage. Although overlap exists, data were formatted into three major categories: anti-inflammatory, vascular, and neuroprotective effects. Based on the amount of information known about the actions of CBD, we hypothesize the anti-inflammatory effects are likely to be the most promising therapeutic mechanism. However, its cardiovascular effects through calcium regulation and its neuroprotective effects against cell death, excitotoxicity, and oxidative stress are all plausible mechanisms by which post-SAH critically ill patients may benefit from both early and late intervention with CBD. More research is needed to better understand if and how CBD might affect neurological and vascular functions in the brain following injury such as subarachnoid hemorrhage.

Prospective study on embolization of intracranial aneurysms with the pipeline device (PREMIER study): 3-year results with the application of a flow diverter specific occlusion classification.

BACKGROUND: The pipeline embolization device (PED; Medtronic) has presented as a safe and efficacious treatment for small- and medium-sized intracranial aneurysms. Independently adjudicated long-term results of the device in treating these lesions are still indeterminate. We present 3-year results, with additional application of a flow diverter specific occlusion scale. METHODS: PREMIER (prospective study on embolization of intracranial aneurysms with pipeline embolization device) is a prospective, single-arm trial. Inclusion criteria were patients with unruptured wide-necked intracranial aneurysms ≤12 mm. Primary effectiveness (complete aneurysm occlusion) and safety (major neurologic event) endpoints were independently monitored and adjudicated. RESULTS: As per the protocol, of 141 patients treated with a PED, 25 (17.7%) required angiographic follow-up after the first year due to incomplete aneurysm occlusion. According to the Core Radiology Laboratory review, three (12%) of these patients progressed to complete occlusion, with an overall rate of complete aneurysm occlusion at 3 years of 83.3% (115/138). Further angiographic evaluation using the modified Cekirge-Saatci classification demonstrated that complete occlusion, neck residual, or aneurysm size reduction occurred in 97.1%. The overall combined safety endpoint at 3 years was 2.8% (4/141), with only one non-debilitating major event occurring after the first year. There was one case of aneurysm recurrence but no cases of delayed rupture in this series. CONCLUSIONS: The PED device presents as a safe and effective modality in treating small- and medium-sized intracranial aneurysms. The application of a flow diverter specific occlusion classification attested the long-term durability with higher rate of successful aneurysm occlusion and no documented aneurysm rupture. TRIAL REGISTRATION: NCT02186561.

Translating Animal Models of Ischemic Stroke to the Human Condition.

Ischemic stroke is a leading cause of death and disability. However, very few neuroprotective agents have shown promise for treatment of ischemic stroke in clinical trials, despite showing efficacy in many successful preclinical studies. This may be attributed, at least in part, to the incongruency between experimental animal stroke models used in preclinical studies and the manifestation of ischemic stroke in humans. Most often the human population selected for clinical trials are more diverse than the experimental model used in a preclinical study. For successful translation, it is critical to develop clinical trial designs that match the experimental animal model used in the preclinical study. This review aims to provide a comprehensive summary of commonly used animal models with clear correlates between rodent models used to study ischemic stroke and the clinical stroke pathologies with which they most closely align. By improving the correlation between preclinical studies and clinical trials, new neuroprotective agents and stroke therapies may be more accurately and efficiently identified.

Surgical management of petrous apex cholesteatomas in the pediatric population: A systematic review.

Background: Cholesteatomas are growths of squamous epithelium that can form inside the middle ear and mastoid cavity and damage nearby structures causing hearing loss when located at the petrous apex. The primary goal of petrous apex cholesteatoma resection is gross total removal with tympanoplasty and canal-wall up or canal-wall down tympanomastoidectomy. At present, there is no definitive surgical approach supported by greater than level 4 evidence in the literature to date. Methods: A systematic review was conducted utilizing PubMed, Embase, and Scopus databases. Articles were screened and selected to be reviewed in full text. The articles that met inclusion criteria were reviewed for relevant data. Data analysis, means, and standard deviations were calculated using Microsoft Excel. Results: After screening, five articles were included in the systematic review. There were a total of eight pediatric patients with nine total cholesteatomas removed. Conductive hearing loss was the most common (77%) presenting symptom. Perforations were noted in seven ears (86%). Recurrence was noted in 50% of patients with an average recurrence rate of 3.5 years (SD = 1.73). Average length of follow-up was 32.6 months (SD = 21.7). Canal-wall up was the most utilized technique (60%) and there were zero noted surgical complications. Five of the seven (71%) patients that experienced hearing loss from perforation noted improved hearing. Conclusion: Due to its rarity, diagnostic evaluation and treatment can vary. Further, multi-institutional investigation is necessary to develop population-level management protocols for pediatric patients affected by petrous apex cholesteatomas.

Simultaneous transarterial and transvenous contrast injection to reveal the fistulous point in carotid cavernous fistula: illustrative case.

BACKGROUND: Access of the cavernous sinus (CS) via venous route from the inferior petrosal sinus (IPS) can sometimes be challenging during the treatment of carotid cavernous fistulas (CCF), largely because of anatomical variations, tortuosity, and/or difficult visualization of IPS given high retrograde flow through the fistulous connection. OBSERVATIONS: A 58-year-old male was transferred to our university hospital center after suspected diagnosis of CCF at another hospital by head computerized tomography-angiogram. His symptoms included three weeks of right eye pain that was later complicated by redness, diplopia, and blurry vision. In a diagnostic angiogram, separate contrast injections from the arterial side via internal carotid artery (ICA) and from the venous side via IPS did not reveal a connection point. Injecting contrast simultaneously from both arterial and venous ends resulted in visualization of a connection point allowing entry into the CS. LESSONS: Technique of simultaneous contrast injection from ICA and internal jugular vein is comparatively simple and saves an operator prolonged time and complexity of approach. In our case, it revealed fistulous point allowing navigation and completing the coiling.

Plasma protein alterations during human large vessel stroke: A controlled comparison study.

BACKGROUND: Stroke is a major cause of death and disability in the United States. Mechanical thrombectomy (MT) and tissue plasminogen activator are the current treatments for ischemic stroke, which have improved clinical outcomes. Despite these treatments, functional and cognitive deficits still occur demonstrating a need for predictive biomarkers for beneficial clinical outcomes which can be used as therapeutic targets for pharmacotherapy. The aim of this study compares the proteomic expression of systemic arterial blood collected at the time of MT to those from a matched cerebrovascular disease (CVD) control cohort. METHODS: The Blood And Clot Thrombectomy Registry And Collaboration (BACTRAC) (clinicaltrials.gov NCT03153683) collects and banks arterial blood, both distal and proximal to the thrombus, from ischemic stroke subjects undergoing MT. Arterial blood from patients undergoing a diagnostic angiogram was also collected and banked as CVD controls. Changes in cardiometabolic and inflammatory proteins between stroke and CVD controls were analyzed via Olink Proteomics. RESULTS: Proteins including ARTN, TWEAK, HGF, CCL28, FGF-5, CXCL9, TRANCE and GDNF were found to be decreased in stroke subjects when compared to CVD controls. CXCL1, CCL5, OSM, GP1BA, IL6, MMP-1, and CXCL5 were increased in stroke subjects when compared to CVD controls. These proteins were also significantly correlated to stroke outcome metrics such as NIHSS, infarct volume and MoCA scoring. CONCLUSION: Overall, acute stroke patients had an increase in inflammatory proteins with a decrease in trophic proteins systemically compared to matched CVD controls. Using our CVD controls, proteins of interest were directly compared to stroke patients with the same cerebrovascular risk factors instead of statistically controlling for comorbidities. The novel methodology of matching an arterial blood CVD control group to a stroke group, as well as controlling for age and comorbid status add to the literature on prognostic stroke biomarkers, which are specific targets for future therapeutics.