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.

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.

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.

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.

Complications of transradial versus transfemoral access for neuroendovascular procedures: a meta-analysis.

BACKGROUND: Transradial access (TRA) has gained increased usage among neurointerventionalists. However, the overall safety profile of access site complications (ASCs) and non-access site complications (NASCs) of TRA versus transfemoral access (TFA) for neuroendovascular procedures remains unclear. METHODS: A systematic literature review and meta-analysis using a random effects model was conducted to investigate the pooled odds ratios (OR) of ASCs and NASCs. Randomized, case-control, and cohort studies comparing access-related complications were analyzed. An assessment of study heterogeneity and publication bias was also completed. RESULTS: Seventeen comparative studies met the inclusion criteria for final analysis. Overall, there was a composite ASC rate of 1.8% (49/2767) versus 3.2% (168/5222) for TRA and TFA, respectively (P<0.001). TRA was associated with a lower odds of ASC compared with TFA (OR 0.42; 95% CI 0.25 to 0.68, P<0.001, I2=31%). There was significantly lower odds of complications within the intervention and diagnostic subgroups. For NASC, TRA had a lower composite incidence of complications than TFA at 1.2% (31/2586) versus 4.2% (207/4909), P<0.001). However, on meta-analysis, we found no significant difference overall between TRA and TFA for NASCs (OR 0.79; 95% CI 0.51 to 1.22, P=0.28, I2=0%), which was also the case on subgroup analysis. CONCLUSION: On meta-analysis, the current literature indicates that TRA is associated with a lower incidence of ASCs compared with TFA, but is not associated with a lower rate of NASCs.