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.

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.

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.

Endovascular Treatment and Thrombolysis for Acute Ischemic Stroke in Patients With Premorbid Disability or Dementia: A Scientific Statement From the American Heart Association/American Stroke Association.

Patients with premorbid disability or dementia have generally been excluded from randomized controlled trials of reperfusion therapies such as thrombolysis and endovascular therapy for acute ischemic stroke. Consequently, stroke physicians face treatment dilemmas in caring for such patients. In this scientific statement, we review the literature on acute ischemic stroke in patients with premorbid disability or dementia and propose principles to guide clinicians, clinician-scientists, and policymakers on the use of acute stroke therapies in these populations. Recent clinical-epidemiological studies have demonstrated challenges in our concept and measurement of premorbid disability or dementia while highlighting the significant proportion of the general stroke population that falls under this umbrella, risking exclusion from therapies. Such studies have also helped clarify the adverse long-term clinical and health economic consequences with each increment of additional poststroke disability in these patients, underscoring the importance of finding strategies to mitigate such additional disability. Several observational studies, both case series and registry-based studies, have helped demonstrate the comparable safety of endovascular therapy in patients with premorbid disability or dementia and in those without, complementing similar data on thrombolysis. These data also suggest that such patients have a substantial potential to retain their prestroke level of disability when treated, despite their generally worse prognosis overall, although this remains to be validated in higher-quality registries and clinical trials. By pairing pragmatic and transparent decision-making in clinical practice with an active pursuit of high-quality research, we can work toward a more inclusive paradigm of patient-centered care for this often-neglected patient population.

Antimicrobial protein REG3A and signaling networks are predictive of stroke outcomes.

Regenerating Family Member 3 Alpha (REG3A) is a multifunctional protein with antimicrobial activity, and primarily secreted by the intestine and pancreas. Studies have shown an increased expression of REG3A in systemic inflammatory responses to acute injury and infection, but studies investigating REG3A during the pathogenesis of ischemic stroke are limited. The aims of this study were to examine the associations between arterial expression of REG3A and other arterial inflammatory proteins implicated in stroke pathogenesis, as well as associations between REG3A and markers of poor outcome for ischemic stroke. The University of Kentucky Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (clinicaltrials.gov NCT03153683) utilizes thrombectomy to isolate intracranial arterial blood (i.e. distal to thrombus) and systemic arterial blood (i.e. carotid). Samples were analyzed by Olink Proteomics for N = 42 subjects. Statistical analyses of plasma proteins included 2-sample t-tests, spearman and biserial correlations, and robust regression models to elucidate network signaling and association to clinical outcomes. Results indicated that levels of systemic REG3A were positively correlated with inflammatory proteins interleukin IL6 (R = 0.344, p = 0.030) and IL17C (R = 0.468, p = 0.002). 2-sided t- tests examining differences of systemic REG3A within quartiles of NIHSS admission score depicted significant differences between quartiles. Those with NIHSS scores corresponding to moderate and moderate-severe neurofunctional deficits had significantly higher levels of systemic REG3A compared to those with NIHSS scores corresponding to mild and mild-moderate neurofunctional deficits (p = 0.016). STRING analyses of proteins in each robust regression model demonstrated substantial networking between REG3A and other systemic proteins highly relevant to ischemic stroke. The present study provides novel data on systemic REG3A in the context of ischemic stroke. These results demonstrate the influential role of REG3A regarding surrogate functional and radiographic outcomes of stroke severity. Additionally, they provide novel insight into the role of REG3A and related proteins during the complex neuroinflammatory process of ischemic stroke. These data provide a foundation for future studies to investigate REG3A and related networking proteins as potential biomarkers with prognostic potential, as well as potential therapeutic targets.

Clinical validation of novel lightning dose optimizer for gamma knife radiosurgery of irregular-shaped arteriovenous malformations and pituitary adenomas.

PURPOSE: To demonstrate the clinical feasibility of a novel treatment planning algorithm via lightning dose optimizer (LDO) on Leksell Gamma Knife (LGK) GammaPlan with significantly faster planning times for stereotactic radiosurgery (SRS) of the complex and difficult arteriovenous malformations (AVMs) and pituitary adenomas. METHODS AND MATERIALS: After completing the in-house end-to-end phantom testing and independent dose verification of the recently upgraded LDO algorithm on GammaPlan using the MD Anderson's IROC anthropomorphic SRS head phantom irradiation credentialing, 20 previously treated GK-SRS patients (10 AVM, average volume 3.61 cm3 and 10 pituitary adenomas, average volume 0.86 cm3 ) who underwent manual forward planning on GammaPlan were retrospectively replanned via LDO. These pathologies were included because of the need for adequate dose delivery with organs at risk in very close proximity. LDO finds the target curvature boundary by well-formulated linear programing objectives and inversely optimizes the GK-SRS plan by isocenter placement, optimization, and sequencing. For identical target coverage, the LDO and original manual plans were compared for target conformity, gradient index, dose to critical organs, and surrounding normal brain. Additionally, various treatment delivery parameters, including beam-on time were recorded. RESULTS: For both patient cohorts, LDO provided similar target coverage with better dose conformity, tighter radiosurgical dose distribution with a lower value of gradient indices (all p < 0.001), and lower dose to critical organs. For AVMs, there was a significant reduction of normal brain V10Gy , V12Gy , and V14Gy by 4.74, 3.67, and 2.67 cm3 (all p < 0.001). LDO had twice the number of shots (p < 0.001), and longer beam-on time (p = 0.012) by a factor of 1.44. For pituitary adenomas, LDO provided systematically lower values of V10Gy , V12Gy , and V14Gy by 1.08, 0.86, and 0.68 cm3 (all p < 0.001), and lower maximum dose to optic pathway by 0.7 Gy (p = 0.005), but had almost twice the numbers of shots (p < 0.001) and increased beam-on time (p = 0.005) by a factor of 1.2. However, for both patient groups, the average planning time for the LDO was <5 min, compared to the estimated 30-90 min of manual planning times. CONCLUSION: GK-SRS treatment on Leksell Perfexion GammaPlan using the LDO provided highly conformal target coverage with a steep dose gradient, spared critical organs, and significantly reduced normal brain dose for complex targets at the cost of slightly higher treatment times. LDO generated high-quality treatment plans and could significantly reduce planning time. If available, the LDO algorithm is suggested for validation and clinical use for complex and difficult GK cases.

Intracranial VCAM1 at time of mechanical thrombectomy predicts ischemic stroke severity.

BACKGROUND: Emergent large vessel occlusion (ELVO) strokes are devastating ischemic vascular events for which novel treatment options are needed. Using vascular cell adhesion molecule 1 (VCAM1) as a prototype, the objective of this study was to identify proteomic biomarkers and network signaling functions that are potential therapeutic targets for adjuvant treatment for mechanical thrombectomy. METHODS: The blood and clot thrombectomy and collaboration (BACTRAC) study is a continually enrolling tissue bank and registry from stroke patients undergoing mechanical thrombectomy. Plasma proteins from intracranial (distal to clot) and systemic arterial blood (carotid) were analyzed by Olink Proteomics for N=42 subjects. Statistical analysis of plasma proteomics used independent sample t tests, correlations, linear regression, and robust regression models to determine network signaling and predictors of clinical outcomes. Data and network analyses were performed using IBM SPSS Statistics, SAS v 9.4, and STRING V11. RESULTS: Increased systemic (p<0.001) and intracranial (p=0.013) levels of VCAM1 were associated with the presence of hypertension. Intracranial VCAM1 was positively correlated to both infarct volume (p=0.032; r=0.34) and edema volume (p=0.026; r=0.35). The %∆ in NIHSS from admittance to discharge was found to be significantly correlated to both systemic (p=0.013; r = -0.409) and intracranial (p=0.011; r = -0.421) VCAM1 levels indicating elevated levels of systemic and intracranial VCAM1 are associated with reduced improvement of stroke severity based on NIHSS from admittance to discharge. STRING-generated analyses identified biologic functional descriptions as well as function-associated proteins from the predictive models of infarct and edema volume. CONCLUSIONS: The current study provides novel data on systemic and intracranial VCAM1 in relation to stroke comorbidities, stroke severity, functional outcomes, and the role VCAM1 plays in complex protein-protein signaling pathways. These data will allow future studies to develop predictive biomarkers and proteomic targets for drug development to improve our ability to treat a devastating pathology.

A DELPHI consensus statement on antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of mechanical thrombectomy.

PURPOSE: There is little data and lack of consensus regarding antiplatelet management for intracranial stenting due to underlying intracranial atherosclerosis in the setting of endovascular treatment (EVT). In this DELPHI study, we aimed to assess whether consensus on antiplatelet management in this situation among experienced experts can be achieved, and what this consensus would be. METHODS: We used a modified DELPHI approach to address unanswered questions in antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT. An expert-panel (19 neurointerventionalists from 8 countries) answered structured, anonymized on-line questionnaires with iterative feedback-loops. Panel-consensus was defined as agreement ≥ 70% for binary closed-ended questions/≥ 50% for closed-ended questions with > 2 response options. RESULTS: Panel members answered a total of 5 survey rounds. They acknowledged that there is insufficient data for evidence-based recommendations in many aspects of antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT. They believed that antiplatelet management should follow a standardized regimen, irrespective of imaging findings and reperfusion quality. There was no consensus on the timing of antiplatelet-therapy initiation. Aspirin was the preferred antiplatelet agent for the peri-procedural period, and oral Aspirin in combination with a P2Y12 inhibitor was the favored postprocedural regimen. CONCLUSION: Data on antiplatelet management for intracranial stenting due to underlying atherosclerosis in the setting of EVT are limited. Panel-members in this study achieved consensus on postprocedural antiplatelet management but did not agree upon a preprocedural and intraprocedural antiplatelet regimen. Further prospective studies to optimize antiplatelet regimens are needed.

Changes in Angioarchitecture After Stereotactic Radiosurgery for Dural Arteriovenous Fistula.

INTRODUCTION: Dural arteriovenous fistulae (DAVF) are intracranial vascular abnormalities encountered in neurosurgery practice. Treatment options are microsurgical disconnection, endovascular embolization and/or radiosurgery. Past studies have reported the efficacy, safety, and predictors of success of radiosurgery. In this study, we investigated the angioarchitecture of fistulae at the time of radiosurgery and how the anatomy changed in the time after treatment based on angiogram follow-ups. METHODS: A retrospective analysis was performed on patients with angiographic diagnosis of DAVF treated with Gamma Knife radiosurgery (GKRS) between 2013 and 2018. Data collection included demographics, symptoms, grading scores, vascular anatomy, radiation data, treatment strategy, angiographic results, and length of patient follow-up. RESULTS: Our study reports data on 10 patients with a total of 14 fistulae. On follow-up angiography, 8 (57%) had complete occlusion of the fistula with a median time to follow up of 19.5 months. The remaining 6 (43%) were deemed as near-complete occlusion of fistula with a median time to follow up of 12.0 months. Time from radiosurgery to angiogram revealing incomplete vs. angiogram revealing complete obliteration was significantly different (p=0.045). Nearly all AVFs had decreased feeders over time after treatment with only one AVF developing an additional feeder post-treatment. Arterial feeders, drainage site, sex, Borden type, lesion volume and treatment volume had no predictive value of obliteration outcome. CONCLUSIONS: This study provides data on the angioarchitecture of fistulae treated with GKRS and also serves as an extension of previous studies reporting the safety and efficacy of GKRS treatment for DAVF in a specific patient population.

Prehospital Triage of Acute Stroke Patients During the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic has broad implications on stroke patient triage. Emergency medical services providers have to ensure timely transfer of patients while minimizing the risk of infectious exposure for themselves, their co-workers, and other patients. This statement paper provides a conceptual framework for acute stroke patient triage and transfer during the COVID-19 pandemic and similar healthcare emergencies in the future.

Early acid/base and electrolyte changes in permanent middle cerebral artery occlusion: Aged male and female rats.

BACKGROUND: Early changes in acid/base and electrolyte concentrations could provide insights into the development of neuropathology at the onset of stroke. We evaluated associations between acid/base and electrolyte concentrations, and outcomes in permanent middle cerebral artery occlusion (pMCAO) model. METHODS: 18-month-old male and female Sprague-Dawley rats underwent pMCAO. Pre-, post- (7 min after occlusion), and at 72 hr of pMCAO venous blood samples provided pH, carbon dioxide, oxygen, glucose, hematocrit, hemoglobin, and electrolyte values of ionized calcium, potassium, and sodium. Multiple linear regression determined predictors of infarct and edema volumes from these values, Kaplan-Meier curve analyzed morality between males and females at 72 hr, and a Cox regression model was used to determine predictors for mortality. RESULTS: Analysis indicated significant differences in acid/base balance and electrolyte levels in aged rats not dependent on sex between the three time points in the pMCAO model. Changes in pH (from pre- to post and post- to 72 hr) and changes in sodium and ionized calcium (from post- to 72 hr) were predictors of infarct volume and edema volume, respectively. Cox Regression revealed there is a 3.25 times increased risk for mortality based on changes in bicarbonate (pre- to post-MCAO). CONCLUSIONS: These early venous blood changes in acid/base balance and electrolytes can be used to predict stroke outcomes in our rat model of stroke. This study provides potential biomarkers to be examined in the human condition that could provide profound prognostic tools for stroke patients.

High Prevalence of Moyamoya Syndrome in Appalachia.

INTRODUCTION: Moyamoya is a chronic cerebrovascular condition of unclear etiology characterized by progressive occlusion of 1 or both internal carotid arteries with neovascular collateral formation. With both an idiopathic form (moya-moya disease) and congenital condition-associated form (moyamoya syndrome), it can cause ischemic and hemorrhagic stroke. Recent findings in Kentucky have challenged traditional estimates of its incidence in US populations. Using the Kentucky Appalachian Stroke Registry (KApSR), our aim was to further characterize its incidence as a cause of stroke and to understand the patient population in Appalachia. METHODS: A retrospective review of moyamoya patients was performed using the KApSR database. Data collected included demographics, county location, risk factors, comorbidities, and health-care encounters from January 1, 2012, to December 31, 2016. RESULTS: Sixty-seven patients were identified; 36 (53.7%) resided in Appalachian counties. The cohort accounted for 125 of 6,305 stroke admissions, representing an incidence of 1,983 per 100,000 stroke admissions. Patients presented with ischemic strokes rather than hemorrhagic strokes (odds ratio 5.50, 95% CI: 2.74-11.04, p < 0.01). Eleven patients (16.4%) exhibited autoimmune disorders. Compared to the general population with autoimmune disorder prevalence of 4.5%, the presence of autoimmunity within the cohort was significantly higher (p < 0.01). Compared to non-Appalachian patients, Appalachian patients tended to present with lower frequencies of tobacco use (p = 0.08), diabetes mellitus (p = 0.13), and hypertension (p = 0.16). CONCLUSIONS: Moyamoya accounts for a substantial number of stroke admissions in Kentucky; these patients were more likely to develop an ischemic stroke rather than a hemorrhagic stroke. Autoimmune disorders were more prevalent in moyamoya patients than in the general population. The reduced frequency of traditional stroke risk factors within the Appalachian group suggests an etiology distinct to the population.

Time Intervals for Direct Versus Transfer Cases of Thrombectomy for Stroke in a Primarily Rural System of Care.

BACKGROUND: Early treatment is the key to a successful recovery for ischemic stroke patients. From time of onset, a patient's chances of permanent disability only increase until they can receive reperfusion intervention. OBJECTIVE: We sought to identify potential delays that occur during evaluation and treatment of patients in a rural regional health system. METHODS: We conducted a single-center retrospective review of all patients that arrived at our comprehensive stroke center (CSC) between July 2011 and March 2017, and received thrombectomy, with or without prior treatment with intravenous recombinant tissue plasminogen activator. RESULTS: One hundred and fifty-four patients met our criteria for inclusion. Patients were divided into 2 groups: Direct (patients brought to our CSC from scene) and Transfer (patients taken to an outside hospital then transferred to our CSC). The median time to CSC for Direct patients was 82 (range: 15-863) minutes after onset of symptoms, compared to 237 (range: 98-1215) minutes for the Transfer group. The median time for Transfer patients to reach an outside hospital was 74 (range: 5-840) minutes, with an additional average time of 90 minutes in the outside hospital prior to transferred to our CSC. CONCLUSIONS: Based on our findings, patients brought directly to our CSC saved a significant amount of time, which may improve functional outcomes. Both groups (Direct and Transfer) spent a similar amount of time between last known normal and emergency medical services arrival, highlighting the need for increased awareness among the public to activate the stroke system of care.

Interleukin 1 alpha administration is neuroprotective and neuro-restorative following experimental ischemic stroke.

BACKGROUND: Stroke remains a leading cause of death and disability worldwide despite recent treatment breakthroughs. A primary event in stroke pathogenesis is the development of a potent and deleterious local and peripheral inflammatory response regulated by the pro-inflammatory cytokine interleukin-1 (IL-1). While the role of IL-1ß (main released isoform) has been well studied in stroke, the role of the IL-1α isoform remains largely unknown. With increasing utilization of intravenous tissue plasminogen activator (t-PA) or thrombectomy to pharmacologically or mechanically remove ischemic stroke causing blood clots, respectively, there is interest in pairing successful cerebrovascular recanalization with neurotherapeutic pharmacological interventions (Fraser et al., J Cereb Blood Flow Metab 37:3531-3543, 2017; Hill et al., Lancet Neurol 11:942-950, 2012; Amaro et al., Stroke 47:2874-2876, 2016). METHODS: Transient stroke was induced in mice via one of two methods. One group of mice were subjected to tandem ipsilateral common carotid artery and middle cerebral artery occlusion, while another group underwent the filament-based middle cerebral artery occlusion. We have recently developed an animal model of intra-arterial (IA) drug administration after recanalization (Maniskas et al., J Neurosci Met 240:22-27, 2015). Sub groups of the mice were treated with either saline or Il-1α, wherein the drug was administered either acutely (immediately after surgery) or subacutely (on the third day after stroke). This was followed by behavioral and histological analyses. RESULTS: We now show in the above-mentioned mouse stroke models (transient tandem ipsilateral common carotid artery (CCA) and middle cerebral artery occlusion (MCA) occlusion, MCA suture occlusion) that IL-1α is neuroprotective when acutely given either intravenously (IV) or IA at low sub-pathologic doses. Furthermore, while IV administration induces transient hemodynamic side effects without affecting systemic markers of inflammation, IA delivery further improves overall outcomes while eliminating these side effects. Additionally, we show that delayed/subacute IV IL-1α administration ameliorates functional deficit and promotes neurorepair. CONCLUSIONS: Taken together, our present study suggests for the first time that IL-1α could, unexpectedly, be an effective ischemic stroke therapy with a broad therapeutic window.

Evaluation of Patients with High National Institutes of Health Stroke Scale as Thrombectomy Candidates Using the Kentucky Appalachian Stroke Registry.

INTRODUCTION: Mechanical thrombectomy has become standard of care for emergent large vessel occlusive stroke. Estimates of incidence for thrombectomy eligibility vary significantly. National Institutes of Health Stroke Scale (NIHSS) of 10 or greater is highly predictive of large vessel occlusion. Using our Kentucky Appalachian Stroke Registry (KApSR), we evaluated temporal trends in stroke admissions with NIHSS ≥10 to determine patient characteristics among that group along with effects and needs in thrombectomy utilization. METHODS: Using the KApSR database that captures patients throughout the Appalachian region in our stroke network, we evaluated patients admitted with ischemic stroke with NIHSS ≥10. We recorded demographics, comorbidities, treatment (thrombectomy, decompressive craniectomy), and county of origin. Change in NIHSS from admission to discharge was used as an indicator of inpatient outcome. RESULTS: Between 2010 and 2016, 1,510 patients were admitted with NIHSS ≥10. 87.2% had high blood pressure, 69.6% had dyslipidemia, and 41.7% used tobacco. There were significant sex differences in the types of patients presenting with NIHSS ≥10 with females being older on average and having more atrial fibrillation and obesity. There was an increase in thrombectomy utilization from 2010 to 2016, but only 7.5% of the potentially eligible patients underwent the procedure. In comparison to the period 2010-2014, the 2015-2016 period had higher rates of obesity and tobacco abuse. CONCLUSION: Among patients with significant burden of ischemic stroke, the most common coexisting medical condition was high blood pressure. Patients who underwent thrombectomy had significantly better inpatient clinical improvement. These data support the need to maximize utilization of thrombectomy along with need to devote increased resources on modifiable stroke risk factors.

Treatment Delays for Patients With Acute Ischemic Stroke in an Iranian Emergency Department: A Retrospective Chart Review.

STUDY OBJECTIVE: We evaluate the extent and nature of treatment delays and the contributing factors influencing them for patients with acute ischemic stroke, as well as main barriers to stroke care in an Iranian emergency department (ED). METHODS: A retrospective chart review was conducted on 394 patients with acute ischemic stroke who were referred to the ED of a tertiary academic medical center in northwest Iran from March 21 to June 21, 2017. The steps of this review process included instrument development, medical records retrieval, data extraction, and data verification. Primary outcomes were identified treatment delays and causes of loss of eligibility for intravenous recombinant tissue plasminogen activator (r-tPA). RESULTS: Of patients with acute ischemic stroke, 80.2% did not meet intravenous r-tPA eligibility; the most common cause was delayed (>4.5 hours) ED arrival after symptom onset (71.82%; n=283). Of 19.8% of subjects for whom the stroke code was activated, intravenous r-tPA was administered in only 5.3%. The average time from patients' arrival to first emergency medicine resident visit, notification of acute stroke team, presence of neurology resident, and computed tomography scan interpretation was lower for patients who met criteria of intravenous r-tPA than for those who lost eligibility for fibrinolytic therapy. The average door-to-needle time was 69 minutes (interquartile range 46 to 91 minutes). CONCLUSION: Our ED and acute stroke team had a favorable clinical performance meeting established critical time goals of inhospital care for potentially eligible patients, but a poor clinical performance for the majority of patients who were not candidates for fibrinolytic therapy.

Systematic Review of Endovascular, Surgical, and Conservative Options for Infectious Intracranial Aneurysms and Cardiac Considerations.

INTRODUCTION: With rising rates of intravenous drug use, Infectious Intracranial aneurysms (IIAs) are a relevant topic for investigation. We performed a systematic review to better understand current practice patterns and limits of current published literature. METHOD: 131 publications with a total of 499 patients (665 aneurysms) were included. Of the 499 patients, 83 were single case reports, and 20.5% of the total had multiple aneurysms. 35.8% of all aneurysms were ruptured. Of those reporting treatment, options included conservative antibiotic therapy (30.0%), open surgical intervention (31.1%), and endovascular occlusion (31.8%). Chronologically, publication of IIAs has increased. Usage of endovascular therapies has grown, while conservative and surgical management have declined in the literature. Overall, 56.2% of aneurysms for which conservative therapy was initiated eventually either underwent intervention or death of patient occurred. RESULTS: The issue of cardiac valve surgery in relationship to aneurysm therapy was discussed in 20.8% (80 patients) of all 384 infectious endocarditis patients; of which 15.0% (12) underwent valve surgery before aneurysm treatment and 85.0 patients (68)% underwent valve surgery after aneurysm treatment. For 51 of the patients where valve surgery followed aneurysm management, the corresponding aneurysm treatment modality could be determined; 58.8% (30) of whom were managed endovascularly. 32.7% (26) of all cases reporting cardiac surgery details underwent cardiac surgery during their admission with the IIA. CONCLUSIONS: Overall, increasing trend of endovascular management of IIAs is evident, and a strong temporal preference exhibited by providers to perform cardiac surgery subsequently to IIA management.

Factors Associated with Moyamoya Syndrome in a Kentucky Regional Population.

OBJECTIVES: Our study aimed to report both new and previously identified conditions associated with moyamoya syndrome in a Western population and to present our outcomes after surgical treatment with indirect bypass. METHODS: We performed a retrospective chart review of patients evaluated at our institution from June 2011 to June 2015 who were diagnosed with moyamoya. Data collected include patient demographics, presenting manifestations, vessels involved, comorbid conditions, abnormal laboratory values, treatments administered, and clinical outcomes. RESULTS: Thirty-one patients with moyamoya were enrolled (11 male and 20 female), with 84% Caucasian and 16% African-American. The most common comorbidity was hypertension in 61% of the patients. Coexisting autoimmune conditions were present in 26%, with another 13% having coexisting prothrombotic disorders. Diabetes mellitus was not found to correlate with the Suzuki grade of disease at presentation (P = .30). When noninvasive imaging was performed before the cerebral angiogram, the computed tomography angiography had a false-negative rate of 59%, and magnetic resonance angiography had a false-negative rate of 33%. Twenty-one patients underwent surgical intervention, 2 underwent intracranial stenting, and 19 underwent indirect bypass with encephaloduroarteriosynangiosis. At an average 28-month follow-up, all 15 patients who had an angiogram after intervention showed evidence of neovascularization. CONCLUSIONS: Autoimmune and prothrombotic disorders were found to be comorbid in patients with moyamoya at much higher rates than expected in the general population. Diabetes mellitus was not significantly correlated with Suzuki grade. Angiogram remains an important diagnostic modality when noninvasive imaging is negative for vasculopathy. We demonstrate excellent evidence of revascularization within 1 year with intracranial stenting and indirect bypass.

The Kentucky Appalachian Stroke Registry (KApSR).

BACKGROUND: The population of rural Kentucky and West Virginia has a disproportionately high incidence of stroke and stroke risk factors. The Kentucky Appalachian Stroke Registry (KApSR) is a novel registry of stroke patients developed to collect demographic and clinical data in real time from these patients' electronic health records. OBJECTIVE: We describe the development of this novel registry and test it for ability to provide the information necessary to identify care gaps and direct clinical management. METHODS: The KApSR was developed as described in this article. To assess utility in patient care, we developed a "Diabetes Quality Assurance Dashboard" by cross-referencing patients in the registry with a diagnosis of ischemic cerebrovascular disease with patients that were tested for hemoglobin A1c (HbA1c) levels, patients with HbA1c levels diagnostic for diabetes mellitus (DM), and patients with an elevated HbA1c that were formally diagnosed with DM. RESULTS: For the 1008 patients treated for ischemic cerebrovascular disease in the year studied, 859 (85%) had their HbA1c tested. Of those, 281 had levels of 6.5 or greater, although only 261 (93%) were discharged with a formal diagnosis of DM. CONCLUSIONS: The KApSR has practical value as a tool to assess a large population of patients quickly for care quality and for research purposes.