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.

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.

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.

Abnormal Course of Internal Carotid Artery Encountered During Neck Dissection.

Internal carotid artery (ICA) is one of the most important structures to be preserved during neck dissection. Many anomalous courses of ICA have been explained and must be kept in mind while proceeding with surgery. The variation mentioned in this article has not been described yet. This is very important for head and neck surgeons, especially while performing neck dissection or external carotid artery ligation. A 51-year-old male with no known comorbidities underwent surgery for carcinoma right buccal mucosa. As noted in preoperative imaging, intraoperatively he had a abnormal course of ICA especially with abnormal relation to the internal jugular vein (IJV). It is imperative to study the anatomy of ICA preoperatively to prevent intraoperative surprises. A careful dissection of the level II cervical region keeping in mind regarding an aberrant course of ICA especially with relation to IJV can prevent catastrophic consequences.