Stroke emboli from patients with atrial fibrillation enriched with neutrophil extracellular traps.

Background: Recent literature has demonstrated remarkable heterogeneity in the composition of acute ischemic stroke (AIS) emboli, which may impact susceptibility to therapy. Objectives: In this study, we explored differences in proteomic composition of retrieved embolic material from patients with stroke with and without atrial fibrillation (AF) (AF+ and AF-, respectively). Methods: The full proteome of retrieved thromboembolic material from 24 patients with AIS was obtained by mass spectrometry. Known marker proteins were assigned groups representing broad classes of embolus components: red blood cells, platelets, neutrophils, eosinophils, histones, complement, and other clotting-associated proteins (eg, fibrinogen). Relative protein abundances were compared between AF+ and AF- samples. Functional implications of differences were explored with gene set enrichment analysis and Gene Ontology enrichment analysis and visualization tool. Results: One hundred sixty-six proteins were differentially expressed between AF+ and AF- specimens. Eight out of the 15 neutrophil proteins (P < .05; fold change, >2) and 4 of the 14 histone proteins were significantly enriched in AF+ emboli (P < .05; fold change, >2). Gene set enrichment analysis revealed a significant representation of proteins from published neutrophil extracellular trap (NET) proteomic gene sets. The most significantly represented functional Gene Ontology pathways in patients with AF involved neutrophil activation and degranulation (P < 1 × 10-7). Conclusion: The present analysis suggests enrichment of NETs in emboli of patients with stroke and AF. NETs are a significant though understudied structural component of thrombi. This work suggests not only unique stroke biology in AF but also potential therapeutic targets for AIS in this population.

Histone content, and thus DNA content, is associated with differential in vitro lysis of acute ischemic stroke clots.

BACKGROUND: Fibrin, von Willebrand factor, and extracellular DNA from neutrophil extracellular traps all contribute to acute ischemic stroke thrombus integrity. OBJECTIVES: In this study, we explored how the proteomic composition of retrieved thromboemboli relates to susceptibility to lysis with distinct thrombolytics. METHODS: Twenty-six retrieved stroke thromboemboli were portioned into 4 segments, with each subjected to 1 hour of in vitro lysis at 37 °C in 1 of 4 solutions: tissue plasminogen activator (tPA), tPA + von Willebrand factor-cleaving ADAMTS-13, tPA + DNA-cleaving deoxyribonuclease (DNase) I, and all 3 enzymes. Lysis, characterized by the percent change in prelysis and postlysis weight, was compared across the solutions and related to the corresponding abundance of proteins identified on mass spectrometry for each of the thromboemboli used in lysis. RESULTS: Solutions containing DNase resulted in approximately 3-fold greater thrombolysis than that with the standard-of-care tPA solution (post hoc Tukey, P < .01 for all). DNA content was directly related to lysis in solutions containing DNase (Spearman's ρ > 0.39 and P < .05 for all significant histones) and inversely related to lysis in solutions without DNase (Spearman's ρ < -0.40 and P < .05 for all significant histones). Functional analysis suggests distinct pathways associated with susceptibility to thrombolysis with tPA (platelet-mediated) or DNase (innate immune system-mediated). CONCLUSION: This study demonstrates synergy of DNase and tPA in thrombolysis of stroke emboli and points to DNase as a potential adjunct to our currently limited selection of thrombolytics in treating acute ischemic stroke.

Comparing Outcomes for Emergent Cranial Neurosurgical Procedures Performed "During Hours" and "After Hours".

OBJECTIVE: Surgery performed at night and on weekends is thought to be associated with increased complications. However, the impact of time of day on outcomes has not been studied within cranial neurosurgery. We aim to determine if there are differences in outcomes for cranial neurosurgery performed after hours (AH) compared with during hours (DH). METHODS: We performed a single-center retrospective study of cranial neurosurgery patients who underwent emergent surgery from January 2015 through December 2019. Surgery was considered DH if the incision occurred between 8 am and 5 pm Monday through Friday. We assessed outcome measures for differences between operations performed DH or AH. RESULTS: Three-hundred and ninety-three patients (114 DH, 279 AH) underwent surgery. There was a lower rate of return to the operating room within 30 days for AH (8.6%) compared with DH (14.0%), P = 0.03, on multivariate analysis. There were no significant differences in length of operation, estimated blood loss, improvement in Glasgow Coma Scale, intensive care unit and total hospital length of stay, 30-day readmission, 30-day mortality, and in-hospital mortality for cases performed DH compared with AH. Further subgroup analyses were performed for patients who underwent immediate surgery for subdural hematomas, with no differences noted in outcomes on multivariate analysis. CONCLUSIONS: This study suggests that operating AH does not appear to negatively impact outcomes when compared with operating DH, in cases of cranial neurosurgical emergencies. Further study assessing the impact on elective neurosurgical cases is required.

Safety and efficacy comparison of embolic agents for middle meningeal artery embolization for chronic subdural hematoma.

OBJECTIVE: To perform a systematic review and meta-analysis evaluating the efficacy of middle meningeal artery embolization in terms of both clinical and radiographic outcomes, when performed with different embolic agents. METHODS: A systematic literature review and meta-analysis was performed to evaluate the impact of embolic agents on outcomes for middle meningeal artery (MMA) embolization. The use of polyvinyl alcohol (PVA) with or without (±) coils, N-butyl cyanoacrylate (n-BCA) ± coils, and Onyx alone were separately evaluated. Primary outcome measures were recurrence, the need for surgical rescue and in-hospital periprocedural complications. RESULTS: Thirty-one studies were identified with a total of 1,134 patients, with 786 receiving PVA, 167 receiving n-BCA, and 181 patients receiving Onyx. There was no difference in the recurrence rate (5.5% for PVA, 4.5% for n-BCA, and 6.5% for Onyx, with P=0.71) or need for surgical rescue (5.0% for PVA, 4.0% for n-BCA, and 6.9% for Onyx, with P=0.89) based on the embolic agent. Procedural complications also did not differ between embolic agents (1.8% for PVA, 3.6% for n-BCA, and 1.6% for Onyx, with P=0.48). CONCLUSIONS: Rates of recurrence, need for surgical rescue, and periprocedural complication following MMA embolization are not impacted by the type of embolic agent utilized. Ongoing clinical trials may be used to further investigate these findings.

Symptomatic carotid artery intraluminal thrombus: risk of medical management failure and distal embolization.

BACKGROUND: Carotid artery intraluminal thrombus (ILT), or free-floating thrombus, is an uncommon cerebrovascular entity with considerable equipoise regarding its clinical management. Likewise, in patients treated with medical management (MM), distal embolization and/or intracranial hemorrhage (ICH) may still occur. METHODS: All patients with symptomatic ILT from 2016 to 2023 were identified from our tertiary care institution. Patients with MM failure (recurrent cerebral ischemia and/or symptomatic ICH) were compared with patients with MM non-failure. Differences in ILT volume and length were calculated. Receiver operator characteristic (ROC) curve analysis was used to identify the cut-off volume and length for risk of MM failure. RESULTS: In total, 45 patients with ILT were identified with 41 treated with frontline MM. Of these 41 patients treated with MM, seven (17%) had MM failure with six (14.6%) having new embolic stroke and one (2.3%) with symptomatic ICH. Patients with MM failure had a significantly higher mean thrombus volume than MM non-failure patients (257 mm3 vs 59.6 mm3, P=0.0006). Likewise, patients with MM failure had significantly longer thrombus on average (21 mm vs 6.6 mm, P=0.0009). ROC curve analysis showed that an ILT volume of 90 mm3 resulted in a sensitivity of 71.4% and specificity of 85.3% for MM failure (AUC 0.775; CI 0.55 to 1.0, P=0.023). CONCLUSIONS: Carotid ILTs that fail MM are significantly larger and longer. These findings suggest that a thrombus volume of 90 mm3 may serve as a guide for intervention with good sensitivity and specificity for risk of MM failure.

Ischemic Stroke Thrombus Perviousness Is Associated with Distinguishable Proteomic Features and Susceptibility to ADAMTS13-Augmented Thrombolysis.

BACKGROUND AND PURPOSE: Perviousness is the differential attenuation on CT of an intracranial arterial occlusive thrombus before and after IV contrast administration. While perviousness/permeability has been shown to be related to various clinical outcomes and reflects histopathologic composition, it remains unclear whether perviousness is also associated with differences in proteomic composition. MATERIALS AND METHODS: Retrieved clots from 59 patients were evaluated with quantitative mass spectrometry. Proteomic differences between high-perviousness (≥11 HU) and low-perviousness (<11 HU) clots were investigated. Perviousness as a continuous variable was also correlated with protein abundance. Last, an ex vivo lysis assay was performed to investigate the differential susceptibility to tPA, deoxyribonuclease, and ADAMTS13 thrombolysis as a function of perviousness. RESULTS: In total, 2790 distinct proteins were identified. Thrombus perviousness was associated with distinct proteomic features, including depletion of the macrophage marker CD14 (P = .039, z = 1.176) and hemoglobin subunit ζ (P = .046, z = 1.68) in pervious clots. Additionally, proteins involved in platelet cytoskeleton remodeling (tropomyosin α-3-chain) and granule secretion/aggregation (synaptotagmin-like protein 4/FC region receptor II-a) were associated with increasing perviousness (P < .006), among numerous other proteins. Monocyte/macrophage-associated proteins (apoptosis-associated specklike protein containing a CARD/SAMHD1) were also depleted in pervious emboli (P < .002). Ex vivo lysis indicated that pervious clots were more susceptible to ADAMTS13-augmented tPA thrombolysis compared with impervious clots (P < .05), though without differences in deoxyribonuclease digestion. CONCLUSIONS: Thrombus perviousness is associated with complex proteomic features, including differential abundance of platelet-related proteins in highly permeable clots with monocyte/macrophage depletion. This association may help to explain why highly pervious thrombi were also found more susceptible to ADAMTS13-augmented thrombolysis.

Comparing 30-Day Outcomes After Emergent Spine Procedures Performed "During Hours" vs "After Hours".

BACKGROUND: Spinal injuries, whether mechanical or neurological, frequently require urgent intervention. Superior outcomes are associated with earlier intervention, which often requires operating overnight and on weekends. However, operating after hours has been associated with increased risks of complications in selected studies. The authors sought to determine whether there are differences in outcomes for "after hours" surgery compared with "during hours" surgery for spinal emergencies. METHODS: This is a single-center retrospective cohort study of spine surgery patients who underwent urgent surgery within 6 hours, from January 2015 through December 2019. Surgery was considered during hours if it started between 8 am and 5 pm Monday through Friday. After hours was defined as from 5 pm through 8 am on a weekday or Saturday or Sunday. We assessed 30-day outcome measures for differences between operations performed during hours or after hours. RESULTS: There were 241 spine procedures performed (49 during hours and 192 after hours). There was no significant difference between the length of operation (145.3 vs 129.8 minutes, P = 0.29), estimated blood loss (303.9 vs 274.4 mL, P = 0.61), improvement in American Spinal Injury Association scale (0.26 vs 0.24 grade, P = 0.85), 30-day return to the operating room (OR; 14.3% vs 6.8%, P = 0.09), 30-day readmission (2.0% vs 6.3% P = 0.24), intensive care unit length of stay (4.6 vs 6.3 days, P = 0.27), hospital length of stay (13.5 days vs 14.2 days, P = 0.72), or 30-day mortality (4.1% vs 7.3%, P = 0.42) for cases performed during hours compared with those after hours, respectively. On multivariate analysis, prior malignancy (P = 0.008) and blue immediate status (P = 0.004) were predictors of 30-day mortality. However, "after hours" surgery was not a predictor of 30-day return to the OR, readmission, or mortality in either univariate or multivariate analysis. CONCLUSIONS: Spine surgery must often be performed after hours. However, the time of day does not significantly impact the 30-day outcomes for emergent spine surgery.

A case of spontaneous basal ganglia hemorrhage with contralateral extension utilizing the canal of Gratiolet.

BACKGROUND: Intracranial hemorrhage accounts for 10-20% of stroke etiologies annually. Basal ganglia is the most common site for intracranial hemorrhage accounting for 50% of all cases. Bilateral spontaneous basal ganglia hemorrhages (BGH) are rare with few reported cases. CASE PRESENTATION: We report an unusual case of a 69-year-old female who presented with a spontaneous bilateral basal ganglia hemorrhage secondary to a right BGH with contralateral extension through the anterior commissure (AC) utilizing the Canal of Gratiolet. Clinical course and imaging findings are discussed. CONCLUSIONS: To our knowledge, this is the first case to specifically detail the extension of spontaneous hemorrhage across the AC via the Canal of Gratiolet, and imaging findings provide a novel depiction of AC anatomy and fiber distribution in a clinical context. These findings may explain the mechanism behind this rare clinical entity.

Carotid Intimal Sarcoma Presenting as Large Vessel Occlusion and Diagnosed by Embolus Histopathology: Case Report.

Objective: The objective of this study was to present the clinical, histopathologic, and radiographic findings of a unique case of intimal sarcoma (IS) embolus presenting as a large vessel occlusion causing an ischemic stroke without a detectable primary tumor site. Methods: Extensive examinations, multimodal imaging, laboratory testing, and histopathologic analysis were used in evaluation. Results: We report the case of a patient who presented with acute embolic ischemic stroke and was found to have IS based on a histopathologic evaluation of his embolectomy specimen. Subsequent comprehensive imaging studies failed to detect a primary tumor site. Multidisciplinary interventions including a course of radiotherapy were performed. The patient died of recurrent multifocal strokes 92 days after diagnosis. Discussion: Meticulous histopathologic analysis should be conducted on cerebral embolectomy specimens. Histopathology may be useful in diagnosing IS.

CT hyperdense cerebral artery sign reflects distinct proteomic composition in acute ischemic stroke thrombus.

BACKGROUND: Hyperdense cerebral artery sign (HCAS) is an imaging biomarker in acute ischemic stroke (AIS) that has been shown to be associated with various clinical outcomes and stroke etiology. While prior studies have correlated HCAS with histopathological composition of cerebral thrombus, it is unknown whether and to what extent HCAS is also associated with distinct clot protein composition. METHODS: Thromboembolic material from 24 patients with AIS were retrieved via mechanical thrombectomy and evaluated with mass spectrometry in order to characterize their proteomic composition. Presence (+) or absence (-) of HCAS on preintervention non-contrast head CT was then determined and correlated with thrombus protein signature with abundance of individual proteins calculated as a function HCAS status. RESULTS: 24 clots with 1797 distinct proteins in total were identified. 14 patients were HCAS(+) and 10 were HCAS(-). HCAS(+) were most significantly differentially abundant in actin cytoskeletal protein (P=0.002, Z=2.82), bleomycin hydrolase (P=0.007, Z=2.44), arachidonate 12-lipoxygenase (P=0.004, Z=2.60), and lysophospholipase D (P=0.007, Z=2.44), among other proteins; HCAS(-) clots were differentially enriched in soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (P=0.0009, Z=3.11), tyrosine-protein kinase Fyn (P=0.002, Z=2.84), and several complement proteins (P<0.05, Z>1.71 for all), among numerous other proteins. Additionally, HCAS(-) thrombi were enriched in biological processes involved with plasma lipoprotein and protein-lipid remodeling/assembling, and lipoprotein metabolic processes (P<0.001), as well as cellular components including mitochondria (P<0.001). CONCLUSIONS: HCAS is reflective of distinct proteomic composition in AIS thrombus. These findings suggest that imaging can be used to identify mechanisms of clot formation or maintenance at the protein level, and might inform future research on thrombus biology and imaging characterization.

Ischemic stroke caused by spontaneous anterior circulation intracranial arterial dissections: patient series.

BACKGROUND: Intracranial arterial dissections (IADs) are classically associated with the vertebrobasilar system, yet are a devastating cause of ischemic stroke within the anterior circulation. Current literature regarding the surgical management of anterior circulation IAD is lacking. As a result, data on 9 patients presenting with ischemic stroke due to spontaneous anterior circulation IAD between 2019 and 2021 were collected in a retrospective manner. Symptoms, diagnostic modalities, treatment, and outcomes are presented for each case. Patients who underwent endovascular procedures had 10-minute follow-up angiography performed to identify signs of reocclusion, which prompted initiation of glycoprotein IIb/IIIa therapy and stent placement. OBSERVATIONS: Seven patients underwent emergent endovascular intervention (stenting: n = 5; thrombectomy alone: n = 2). The remaining 2 were managed medically. Two patients developed progressive flow limiting stenosis requiring further intervention, 2 developed asymptomatic progressive stenosis/occlusion with robust collateral formation and the remainder have patent vasculature upon follow up imaging at 6 to 12 months. Seven patients had a modified Rankin Scale score of 1 or less at the 3-month follow-up. LESSONS: IAD is a devastating yet rare cause of anterior circulation ischemic stroke. The treatment algorithm proposed resulted in positive clinical and angiographic outcomes warranting future consideration and study in the emergent management of spontaneous anterior circulation IAD.

Preoperative Embolization of Meningiomas Facilitates Reduced Surgical Complications and Improved Clinical Outcomes : A Meta-analysis of Matched Cohort Studies.

PURPOSE: The utility of preoperative embolization (PE) of intracranial meningiomas is unclear and controversial. The aim of this study was to investigate the effect of PE on meningioma surgical resection by completing a meta-analysis of matched cohort studies. METHODS: A systematic review and meta-analysis of matched cohort studies was completed to evaluate the effect of PE on meningioma resection and outcomes. Outcome measures included: intraoperative blood loss, major surgical complications, total surgical complications including minor ones, total major complications including major surgical and embolization complications, total overall complications, and postoperative functional independence defined as modified Rankin Score (mRS) of 0-2. Pooled odds ratios (OR) were determined via a fixed effects model. RESULTS: A total of 6 matched cohort studies were identified with 219 embolized and 215 non-embolized meningiomas. There was no significant difference in intraoperative blood loss between the two groups (P = 0.87); however, the embolization group had a significantly lower odds ratio of major surgically related complications (OR: 0.37, 95% confidence interval, CI: 0.21-0.67, P = 0.0009, I2 = 0%), but no difference in minor surgical complications (P = 0.86). While there was a significantly lower odds ratio of total overall surgical and PE-related complications in PE cases (OR: 0.64, CI: 0.41-1.0, P = 0.05, I2 = 66%), there was no difference in total combined major complications between the groups (OR: 0.57, CI: 0.27-1.18, P = 0.13, I2 = 33%). Lastly, PE was associated with a higher odds ratio of functional independence on postoperative follow-up (OR: 2.3, CI: 1.06-5.02, P = 0.04, I2 = 0%). CONCLUSION: For certain meningiomas, PE facilitates lower overall complications, lower major surgical complications, and improved functional independence. Further research is required to identify the particular subset of meningiomas that benefit from PE.

Mechanical Thrombectomy for Ischemic Stroke Secondary to Large Vessel Occlusions in Patients on Extracorporeal Membrane Oxygenation.

INTRODUCTION: The use of short-term mechanical circulatory support (MCS) devices and procedures for function- and life-sustaining therapy is becoming a routine practice at many centers. Concomitant with the increasing use of MCS is the increasing recognition of acute brain injuries, including acute ischemic stroke, which may be caused by a myriad of MCS-driven factors. The aim of this case series was to document our experience with mechanical thrombectomy (MT) for ischemic stroke in extracorporeal membrane oxygenation (ECMO) patients. METHODS: We retrospectively reviewed a prospectively maintained database of patients undergoing endovascular thrombectomy for large vessel occlusion at our institution. We identified patients that were on ECMO and underwent thrombectomy. Baseline demographics and procedural and functional outcomes were collected. RESULTS: Three patients on ECMO were identified to have a large vessel occlusion and underwent thrombectomy. Two patients had an internal carotid artery terminus occlusion and one had a basilar artery occlusion. An mTICI 3 recanalization was achieved in all patients without postoperative hemorrhagic complications. Two patients achieved a 3-month mRS of 1, while one had mRS 4. CONCLUSION: Ischemic stroke can be associated with significant morbidity in MCS patients. We demonstrate that MT can be safely performed in this patient population with good outcomes.

Impact of aspiration catheter size on clinical outcomes in aspiration thrombectomy.

BACKGROUND: Direct aspiration thrombectomy is a well-established method for mechanical thrombectomy in acute ischemic stroke. Yet, the influence of aspiration catheter internal diameter (ID) on aspiration thrombectomy efficacy is incompletely understood. METHODS: A systematic literature review and meta-regression analysis was completed to evaluate the impact of primary aspiration thrombectomy outcomes based on the ID of the aspiration catheter. Primary outcome measures were: final recanalization of modified Thrombolysis In Cerebral Ischemia (mTICI) 2b-3 with aspiration only and with rescue modalities, first pass effect (FPE), need for rescue modalities, intracranial hemorrhagic complication rates, and functional outcomes of 90-day modified Rankin Scale (mRS) of 0-2. RESULTS: 30 studies were identified with 3228 patients. Meta-regression analysis revealed a significant association between increasing aspiration catheter ID and FPE (p=0.032), between ID and final recanalization with aspiration only (p=0.05), and between ID size and recanalization including cases with rescue modalities (p=0.002). Further, subgroup analysis indicated that catheters with an ID ≥0.064 inch had a lower rate of need for rescue than smaller catheters (p=0.013). Additionally, catheters with an ID ≥0.068 inch had a higher rate of intracranial bleeding complications (p=0.025). Lastly, no significant association was found in functional outcomes overall. CONCLUSIONS: Larger aspiration catheters are associated with a higher rate of FPE, final recanalization with only an aspiration catheter, and in cases with rescue modalities, though with a higher rate of hemorrhagic complications. These findings confirm that aspiration catheter size functions as a variable in aspiration thrombectomy, which should be considered in future study and trial design.

Endovascular thrombectomy with or without intravenous thrombolysis in acute basilar artery occlusion ischemic stroke: A meta-analysis.

INTRODUCTION: It is poorly understood if endovascular thrombectomy (EVT) with or without intravenous thrombolysis (IVT) better facilitates clinical outcomes in patients with acute basilar artery occlusion (BAO) ischemic stroke. METHODS: A systematic literature review and meta-analysis was completed to investigate the outcomes of EVT with IVT versus direct EVT alone in acute BAO. Data was collected from the literature and pooled with the authors' institutional experience. The primary outcome measure was 90-day modified Rankin sale (mRS) of 0-2. Secondary measures were successful post-thrombectomy recanalization defined as mTICI ≥2b, 90-day mortality, and rate of symptomatic ICH. RESULTS: Our institutional experience combined with three multicenter studies resulted in a total of 1,127 patients included in the meta-analysis. 756 patients underwent EVT alone, while 371 were treated with EVT+IVT. Patients receiving EVT+IVT had a higher odds of achieving a 90-day mRS of ≤ 2 compared to EVT alone (OR: 1.50, 95% CI 1.15 to 1.95, P =0.002, I2 =0%). EVT+IVT also had a lower odds of 90-day mortality (OR: 0.57, 95% CI 0.37 to 0.89, P=0.01, I2=24%). There was no difference in sICH between the two groups (OR: 1.0, 95% CI: 0.56 to 1.79, P=0.99, I2=0%). There was also no difference in post-thrombectomy recanalization rates defined as mTICI ≥2b (OR: 1.11, 95% CI 0.70 to 1.75, P = 0.65, I2=37%). CONCLUSIONS: On meta-analysis, EVT with bridging IVT results in superior 90-day functional outcomes and lower 90-day mortality without increase in symptomatic ICH. These findings likely deserve further validation in a randomized controlled setting.

Observation versus intervention for Borden type I intracranial dural arteriovenous fistula: A pooled analysis of 469 patients.

BACKGROUND: While it is thought that Borden Type I intracranial dural arteriovenous fistula (dAVF) have a benign clinical course, their management remains controversial. METHODS: A comparative meta-analysis was completed to evaluate the outcomes of intervention verses observation of Borden Type I intracranial dAVF. Outcome measures included: grade progression, worsening symptoms, death due to dAVF, permanent complications other than death, functional independence (mRS 0-2), and rate of death combined with permanent complication, were evaluated. Risk differences (RD) were determined using a random effects model. RESULTS: Three comparative studies combined with the authors' institutional experience resulted in a total of 469 patients, with 279 patients who underwent intervention and 190 who were observed. There was no significant difference in dAVF grade progression between the intervention and observation arms, 1.8% vs. 0.7%, respectively (RD: 0.01, 95% CI: -0.02 to 0.04, P = 0.49), or in symptom progression occurring in 31/279 (11.1%) intervention patients and 11/190 (5.8%) observation patients (RD: 0.03, CI: -0.02 to 0.09, P = 0.28). There was also no significant difference in functional independence on follow up. However, there was a significantly higher risk of dAVF related death, permanent complication from either intervention or dAVF related ICH or stroke in the intervention group (11/279, 3.9%) compared to the observation group (0/190, 0%) (RD: 0.04, CI: 0.1 to 0.06, P = 0.007). CONCLUSION: Intervention of Borden Type I dAVF results in a higher risk of death or permanent complication, which should be strongly considered when deciding on management of these lesions.

Approaches to and outcomes of intra-arterial tPA in embolectomy for large vessel occlusion.

INTRODUCTION: Intra-arterial tissue plasminogen activator (IA tPA) is sometimes used in conjunction with aspiration catheters and stentrievers to achieve recanalization in endovascular thrombectomy (ET) for large vessel occlusion (LVO). Reports of safety and efficacy of this approach are limited by technical heterogeneity and sample size. METHODS: We retrospectively reviewed a data set of patients undergoing ET for LVO between August 2017 and September 2020 to identify those that received IA tPA. IA tPA usage, timing and dosage was at the discretion of the operative neurosurgeon. We identified three broad categories of IA tPA administration: (1) adjunctive with the first pass; (2) salvage with subsequent passes after first pass achieved incomplete revascularization; and (3) post-thrombectomy residual distal occlusions. Univariate and multivariate logistic regression were performed to test associations with recanalization, hemorrhage, and functional independence. RESULTS: Among 271 patients, 158 (58%) patients had IA tPA, of which 83 received adjuvant IA tPA, 60 received salvage IA tPA, and 15 received post-thrombectomy IA tPA for distal occlusions. There were no differences in demographics, stroke etiology and premorbid medications between these groups. Patients receiving salvage IA tPA had longer times from groin access to recanalization and more passes, as expected. On multivariate analysis neither adjunctive nor salvage IA tPA was significantly associated with recanalization, post-operative hemorrhage, or functional outcomes. On univariate analysis, patients receiving salvage IA tPA had lower rates of TICI 3 or 2b revascularization (80% vs. 89% adjunctive and 92% no IA tPA, p =  0.003) and higher rates of any postoperative hemorrhage (33% vs. 22% adjunctive and 19% no IA tPA, p =  0.003). CONCLUSIONS: In this retrospective, single-institution series, IA tPA used adjunctively or as salvage therapy in ET for LVO was not associated with recanalization, post-operative hemorrhage, or functional outcomes, suggesting IA tPA is an available modality that can be utilized in cases of recalcitrant clots.

High-fidelity, simulation-based microsurgical training for neurosurgical residents.

OBJECTIVE: Simulation is increasingly recognized as an important supplement to operative training. The live rat femoral artery model is a well-established model for microsurgical skills simulation. In this study, the authors present an 11-year experience incorporating a comprehensive, longitudinal microsurgical training curriculum into a Canadian neurosurgery program. The first goal was to evaluate training effectiveness, using a well-studied rating scale with strong validity. The second goal was to assess the impact of the curriculum on objective measures of subsequent operating room performance during postgraduate year (PGY)-5 and PGY-6 training. METHODS: PGY-2 neurosurgery residents completed a 1-year curriculum spanning 17 training sessions divided into 5 modules of increasing fidelity. Both perfused duck wing and live rat vessel training models were used. Three modules comprised live microvascular anastomosis. Trainee performance was video recorded and blindly graded using the Objective Structured Assessment of Technical Skills Global Rating Scale. Eleven participants who completed the training curriculum and 3 subjects who had not participated had their subsequent operative performances evaluated when they were at the PGY-5 and PGY-6 levels. RESULTS: Eighteen participants completed 106 microvascular anastomoses during the study. There was significant improvement in 6 measurable skills during the curriculum. The mean overall score was significantly higher on the fifth attempt compared with the first attempt for all 3 live anastomotic modules (p < 0.001). Each module had a different improvement profile across the skills assessed. Those who completed the microvascular skills curriculum demonstrated a greater number of independent evaluations during superficial surgical exposure, deep exposure, and primary maneuvers at the PGY-5 and PGY-6 levels. CONCLUSIONS: High-fidelity microsurgical simulation training leads to significant improvement in microneurosurgical skills. Transfer of acquired skills to the operative environment and durability for at least 3 to 4 years show encouraging preliminary results and are subject to ongoing investigation.

The Complex Relationship Between Cooling Parameters and Neuroprotection in a Model of Selective Hypothermia.

Background: Hypothermia remains the best studied neuroprotectant. Despite extensive positive large and small animal data, side effects continue to limit human applications. Selective hypothermia is an efficient way of applying neuroprotection to the brain without the systemic complications of global hypothermia. However, optimal depth and duration of therapeutic hypothermia are still unknown. We analyzed a large animal cohort study of selective hypothermia for statistical relationships between depth or duration of hypothermia and the final stroke volume. Methods: A cohort of 30 swine stroke subjects provided the dataset for normothermic and selective hypothermic animals. Hypothermic parameters including duration, temperature nadir, and an Area Under the Curve measurement for 34 and 30°C were correlated with the final infarct volumes measured by MRI and histology. Results: Between group comparisons continue to demonstrate a reduction in infarct volume with selective hypothermia. Histologically-derived infarct volumes were 1.2 mm3 smaller in hypothermia-treated pigs (P = 0.04) and showed a similar, but non-significant reduction in MRI (P = 0.15). However, within the selective hypothermia group, more intense cooling, as measured through increased AUC 34 and decreased temperature nadir was associated with larger infarct proportions by MRI [Pearson's r = 0.48 (p = 0.05) and r = -0.59 (p = 0.01), respectively]. Reevaluation of the entire cohort with quadratic regression demonstrated a U-shaped pattern, wherein the average infarct proportion was minimized at 515 degree-minutes (AUC34) of cooling, and increased thereafter. In a single case of direct brain tissue oxygen monitoring during selective hypothermia, brain tissue oxygen strongly correlated with brain temperature reduction over the course of selective hypothermia to 23°C. Conclusions: In a large animal model of selective hypothermia applied to focal ischemia, there is a non-monotone relationship between duration and depth of hypothermia and stroke volume reduction. This suggests a limit to depth or duration of selective hypothermia for optimal neuroprotection. Further research is required to delineate more precise depth and duration limits for selective hypothermia.

Mobile Stroke Unit Operational Metrics: Institutional Experience, Systematic Review and Meta-Analysis.

Background: The available literature on mobile stroke units (MSU) has focused on clinical outcomes, rather than operational performance. Our objective was to establish normalized metrics and to conduct a meta-analysis of the current literature on MSU performance. Methods: Our MSU in upstate New York serves 741,000 people. We present prospectively collected, retrospectively analyzed data from the inception of our MSU in October of 2018, through March of 2021. Rates of transportation/dispatch and MSU utilization were reported. We also performed a meta-analysis using MEDLINE, SCOPUS, and Cochrane Library databases, calculating rates of tPA/dispatch, tPA-per-24-operational-hours ("per day"), mechanical thrombectomy (MT)/dispatch and MT/day. Results: Our MSU was dispatched 1,719 times in 606 days (8.5 dispatches/24-operational-hours) and transported 324 patients (18.8%) to the hospital. Intravenous tPA was administered in 64 patients (3.7% of dispatches) and the rate of tPA/day was 0.317 (95% CI 0.150-0.567). MT was performed in 24 patients (1.4% of dispatches) for a MT/day rate of 0.119 (95% CI 0.074-0.163). The MSU was in use for 38,742 minutes out of 290,760 total available minutes (13.3% utilization rate). Our meta-analysis included 14 articles. Eight studies were included in the analysis of tPA/dispatch (342/5,862) for a rate of 7.2% (95% CI 4.8-9.5%, I2 = 92%) and 11 were included in the analysis of tPA/day (1,858/4,961) for a rate of 0.358 (95% CI 0.215-0.502, I2 = 99%). Seven studies were included for MT/dispatch (102/5,335) for a rate of 2.0% (95% CI 1.2-2.8%, I2 = 67%) and MT/day (103/1,249) for a rate of 0.092 (95% CI 0.046-0.138, I2 = 91%). Conclusions: In this single institution retrospective study and meta-analysis, we outline the following operational metrics: tPA/dispatch, tPA/day, MT/dispatch, MT/day, and utilization rate. These metrics are useful for internal and external comparison for institutions with or considering developing mobile stroke programs.