Minimally invasive keyhole craniotomies for microsurgical clipping of cerebral aneurysms: comparative meta-analysis of the mini-pterional and supraorbital keyhole approaches.

OBJECTIVE: Axel Perneczky is responsible for conceptualizing the "keyhole" philosophy as a new paradigm of minimal invasiveness within cranial neurosurgery. Keyhole neurosurgery aims to limit approach-related traumatization and minimize brain retraction while still enabling the neurosurgeon to achieve operative goals. The supraorbital keyhole craniotomy (SOKC) and minipterional (pterional keyhole, PKC) approaches have become mainstays for clipping intracranial aneurysms. While studies have compared these approaches to the traditional pterional craniotomy for clipping cerebral aneurysms, head-to-head comparisons of these workhorse keyhole approaches remain limited. METHODS: The authors queried three databases per PRISMA guidelines to identify all studies comparing the SOKC to the PKC for microsurgical clipping of cerebral aneurysms. Of 148 unique studies returned on initial query, a total of 5 studies published between 2013 and 2019 met inclusion criteria. Where applicable, quantitative meta-analysis was performed via the Mantel-Haenszel method using Review Manager v5.4 (Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen, Denmark). Risk of bias (ROB) was assessed using the Cochrane ROBINS-I tool, and all studies were assigned a Level of Evidence (I-V). RESULTS: Across all five studies, the mean age ranged from 53.0 to 57.5 years old, and the cohort consisted of more females (n = 403, 60.6%) than males. The proportion of patients presenting with ruptured aneurysmal SAH was comparable between the SOKC and PKC cohorts (p = 0.43). Clipping rate [defined as the rate of successful aneurysm clip deployment with successful intraoperative occlusion] (OR 1.52 [0.49, 4.71], I2 = 0%, p = 0.47), final occlusion rates (OR 1.27 [0.37, 4.32], p = 0.70), and operative durations (SMD 0.33 [-0.83. 1.49], I2 = 97%, p = 0.58) were comparable regardless of approach used. Furthermore, rates of intraoperative rupture (OR 1.51 [0.64, 3.55], I2 = 0, p = 0.34), postoperative hemorrhage (OR 1.49 [0.74, 3.01], I2 = 0, p = 0.26), postoperative vasospasm (OR 0.94 [0.49, 1.80], I2 = 63, p = 0.86), and postoperative infection (OR 0.70 [0.16, 2.99], I2 = 0%, p = 0.63) were equivocal across SOKC and PKC cohorts. CONCLUSION: The PKC and SOKC approaches appear to afford comparable outcomes when used for open microsurgical clipping of cerebral aneurysms in select patients with both ruptured and unruptured aneurysms. Both are associated with excellent clipping and occlusion rates, minimal perioperative complication profiles, and favorable postoperative neurologic outcomes. Further investigations are merited so clinicians can further parse out the indications and contraindications for each keyhole approach.

Endovascular thrombectomy for ischemic stroke with large infarct, short- and long-term outcomes: a meta-analysis of 6 randomised control trials.

Endovascular Thrombectomy (EVT) as first-line treatment of patients with large core ischemic infarct is a subject of debate. A systematic literature search was conducted in four electronic databases for randomized control trials (RCTs) comparing EVT to best medical treatment (BMT) for large core infarcts (ASPECTS ≤ 5). Relevant studies were added after screening for titles, abstracts, and complete text. Meta-analysis was performed. The continuous outcomes were analyzed using the standardized mean difference (SMD) and 95% CI, while the binary outcomes were analyzed using the risk ratio (RR) and 95% confidence interval (CI). A funnel plot was used to visually evaluate publication bias, and if feasible, Egger's test was used to validate. We included 1918 patients from six RCTs that compared EVT plus BMT and BMT alone in patients with large core infarct due to large vessel occlusion in the anterior circulation. There were 946 patients in the EVT group and 972 patients in the BMT group. The one-year outcomes are available for 314 patients in the EVT group and 292 patents in the BMT group from two RCTs. EVT group had statistically significant higher rate of 90-day mRS 0-1 (RR = 3.1, P-value < 0.0001), mRS 0-2 (RR = 2.64, P-value < 0.0001), mRS 0-3 (RR = 1.80, P-value < 0.0001), lower 90-day mean mRS score (SMD = -0.29, P-value < 0.0001), lower 90-day mortality rate (RR = 0.85, P-value = 0.015), and greater early neurological improvement (RR = 2.16, P-value < 0.00001) compared to the BMT group. However, the rates of symptomatic intracerebral hemorrhage (sICH) (RR = 1.76, P-value = 0.01) and any ICH (RR = 2.18, P-value < 0.00001) were higher in EVT group. Our finding showed that EVT plus BMT led to in an absolute improvement of 5%, 12%, and 16% in 90-day mRS 0-1, 0-2, and 0-3, respectively. In addition, patients in EVT plus BMT group had a 3% increased probability of experiencing sICH and were 32% more susceptible to any ICH. Moreover, the one-year mRS 0-2 (RR = 2.16, P-value < 0.00001) and mRS 0-3 (RR = 1.80, P-value < 0.0001) was significantly favor the EVT plus BMT over BMT alone. Although, the one-year mortality rate was not significantly differed between two groups (RR = 0.91, P-value = 0.31). There was no statistically significant difference observed between the EVT plus BMT group and the BMT group concerning new stroke, decompressive craniectomy, and serious adverse events. Combined data from six RCTs shows that EVT plus BMT provides significantly better short- and long-term functional outcomes with minimal increase in symptomatic hemorrhage over BMT in patient with large core infarcts.

Animal Models of Intracranial Aneurysms: History, Advances, and Future Perspectives.

Intracranial aneurysms (IA) are a disease process with potentially devastating outcomes, particularly when rupture occurs leading to subarachnoid hemorrhage. While some candidates exist, there is currently no established pharmacological prevention of growth and rupture. The development of prophylactic treatments is a critical area of research, and preclinical models using animals play a pivotal role. These models, which utilize various species and induction methods, each possess unique characteristics that can be leveraged depending on the specific aim of the study. A comprehensive understanding of these models, including their historical development, is crucial for appreciating the advantages and limitations of aneurysm research in animal models.We summarize the significant roles of animal models in IA research, with a particular focus on rats, mice, and large animals. We discuss the pros and cons of each model, providing insights into their unique characteristics and contributions to our understanding of IA. These models have been instrumental in elucidating the pathophysiology of IA and in the development of potential therapeutic strategies.A deep understanding of these models is essential for advancing research on preventive treatments for IA. By leveraging the unique strengths of each model and acknowledging their limitations, researchers can conduct more effective and targeted studies. This, in turn, can accelerate the development of novel therapeutic strategies, bringing us closer to the goal of establishing an effective prophylactic treatment for IA. This review aims to provide a comprehensive view of the current state of animal models in IA research.

Toward an optimal cadaveric brain model for neurosurgical education: assessment of preservation, parenchyma, vascular injection, and imaging.

OBJECTIVE: We assessed types of cadaveric head and brain tissue specimen preparations that are used in a high throughput neurosurgical research laboratory to determine optimal preparation methods for neurosurgical anatomical research, education, and training. METHODS: Cadaveric specimens (N = 112) prepared using different preservation and vascular injection methods were imaged, dissected, and graded by 11 neurosurgeons using a 21-point scale. We assessed the quality of tissue and preservation in both the anterior and posterior circulations. Tissue quality was evaluated using a 9-point magnetic resonance imaging (MRI) scale. RESULTS: Formalin-fixed specimens yielded the highest scores for assessment (mean ± SD [17.0 ± 2.8]) vs. formalin-flushed (17.0 ± 3.6) and MRI (6.9 ± 2.0). Cadaver assessment and MRI scores were positively correlated (P < 0.001, R2 0.60). Analysis showed significant associations between cadaver assessment scores and specific variables: nonformalin fixation (ß = -3.3), preservation within ≤72 h of death (ß = 1.8), and MRI quality score (ß = 0.7). Formalin-fixed specimens exhibited greater hardness than formalin-flushed and nonformalin-fixed specimens (P ≤ 0.006). Neurosurgeons preferred formalin-flushed specimens injected with colored latex. CONCLUSION: For better-quality specimens for neurosurgical education and training, formalin preservation within ≤72 h of death was preferable, as was injection with colored latex. Formalin-flushed specimens more closely resembled live brain parenchyma. Assessment scores were lower for preparation techniques performed > 72 h postmortem and for nonformalin preservation solutions. The positive correlation between cadaver assessment scores and our novel MRI score indicates that donation organizations and institutional buyers should incorporate MRI as a screening tool for the selection of high-quality specimens.

Racial and Socioeconomic Status among a Patient Population Presenting with Aneurysmal Subarachnoid Hemorrhage versus Unruptured Intracranial Aneurysm: A Single-Center Study.

Racial and socioeconomic health disparities are well documented in the literature. This study examined patient demographics, including socioeconomic status (SES), among individuals presenting with aneurysmal subarachnoid hemorrhage (aSAH) and unruptured intracranial aneurysm (UIA) to identify factors associated with aSAH presentation. A retrospective assessment was conducted of all patients with aSAH and UIA who presented to a large-volume cerebrovascular center and underwent microsurgical treatment from January 2014 through July 2019. Race and ethnicity, insurance type, and SES data were collected for each patient. Comparative analysis of the aSAH and UIA groups was conducted. Logistic regression models were also employed to predict the likelihood of aSAH presentation based on demographic and socioeconomic factors. A total of 640 patients were included (aSAH group, 251; UIA group, 389). Significant associations were observed between race and ethnicity, SES, insurance type, and aneurysm rupture. Non-White race or ethnicity, lower SES, and having public or no insurance were associated with increased odds of aSAH presentation. The aSAH group had poorer functional outcomes and higher mortality rates than the UIA group. Patients who are non-White, have low SES, and have public or no insurance were disproportionately affected by aSAH, which is historically associated with poorer functional outcomes.

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.

Elucidating the pathogenesis behind arteriovenous malformations of the central nervous system: a bibliometric analysis.

Arteriovenous malformations (AVMs) are vascular malformations of the central nervous system (CNS) with potential for significant consequences. The exact pathophysiologic mechanism of AVM formation is not fully understood. This study aims to evaluate bibliometric parameters and citations of the literature of AVMs to provide an overview of how the field has evolved. We performed an electronic search on Web of Science to identify the top 100 published and indexed articles with the highest number of citations discussing the pathogenesis of AVMs. This study yielded 1863 articles, of which the top 100 were selected based on the highest total citation count. These articles included 24% basic science, 46% clinical, and 30% review articles. The most-cited article was a clinical article from 2003, and the most recent was published in 2022. The median number of authors was 6, with the highest being 46 for a clinical article. The top 5 journals were identified, with the highest impact factor being 20.1. 13 countries were identified, with the US contributing the most articles (approximately 70%). Regarding genes of investigation, VEGF was one of the early genes investigated, while more interested in RAS/MAPK has been garnered since 2015. There is a growing interest in AVM genomics and pathogenesis research. While progress has been made in understanding clinical aspects and risk factors, the exact pathophysiological mechanisms and genetic basis of AVM formation remain incompletely understood. Further investigation of key genes in AVM pathogenesis can allow identification of potential therapeutic targets.

Scalp incision technique for decompressive hemicraniectomy: comparative systematic review and meta-analysis of the reverse question mark versus alternative retroauricular and Kempe incision techniques.

Decompressive hemicraniectomy (DHC) is a critical procedure used to alleviate elevated intracranial pressure (ICP) in emergent situations. It is typically performed to create space for the swelling brain and to prevent dangerous and potentially fatal increases in ICP. DHC is indicated for pathologies ranging from MCA stroke to traumatic subarachnoid hemorrhage-essentially any cause of refractory brain swelling and elevated ICPs. Scalp incisions for opening and closing the soft tissues during DHC are crucial to achieve optimal outcomes by promoting proper wound healing and minimizing surgical site infections (SSIs). Though the reverse question mark (RQM) scalp incision has gained significant traction within neurosurgical practice, alternatives-including the retroauricular (RA) and Kempe incisions-have been proposed. As choice of technique can impact postoperative outcomes and complications, we sought to compare outcomes associated with different scalp incision techniques used during DHC. We queried three databases according to PRISMA guidelines in order to identify studies comparing outcomes between the RQM versus "alternative" scalp incision techniques for DHC. Our primary outcome of interest in the present study was postoperative wound infection rates according to scalp incision type. Secondary outcomes included estimated blood loss (EBL) and operative duration. We identified seven studies eligible for inclusion in the formal meta-analysis. The traditional RQM technique shortened operative times by 36.56 min, on average. Additionally, mean EBL was significantly lower when the RQM scalp incision was used. Postoperatively, there was no significant association between DHC incision type and mean intensive care unit (ICU) length of stay (LOS), nor was there a significant difference in predisposition to developing wound complications or infections between the RQM and retroauricular/Kempe incision cohorts. Superficial temporal artery (STA) preservation and reoperation rates were collected but could not be analyzed due to insufficient number of studies reporting these outcomes. Our meta-analysis suggests that there is no significant difference between scalp incision techniques as they relate to surgical site infection and wound complications. At present, it appears that outcomes following DHC can be improved by ensuring that the bone flap is large enough to enable sufficient cerebral expansion and decompression of the temporal lobe, the latter of which is of particular importance. Although previous studies have suggested that there are several advantages to performing alternative scalp incision techniques during DHC, the present study (which is to our knowledge the first to meta-analyze the literature on outcomes in DHC by scalp incision type) does not support these findings. As such, further investigations in the form of prospective trials with high statistical power are merited.

Mandibular Fossa Approach to Petroclival and Anterior Pontine Lesions.

Objective To describe the anatomy related to a novel approach to the petroclival region through the mandibular fossa for the treatment of petroclival and anterior pontine lesions. Design Five dry skulls were examined for surgical approach. Three adult cadaveric heads underwent bilateral dissection. One cadaveric head was evaluated with computed tomography after dissection. Setting This study was performed in an academic medical center. Participants Neurosurgical anatomy researchers performed this study using dry skulls and cadaveric heads. Main Outcome Measurements This was a proof-of-concept anatomical study. Results The mandibular fossa approach uses a vertical preauricular incision above the facial nerve branches. Removal of the temporomandibular joint exposes the mandibular fossa. The anterior boundary is the mandibular nerve at the foramen ovale, and the posterior boundary is the jugular foramen. The chorda tympani, eustachian tube, and tensor tympani muscle are sectioned. The carotid artery is transposed out of the petrous canal, and a petrosectomy is performed from Meckel's cave to the foramen magnum and anterior occipital condyle. Dural opening exposes the anterior pons, vertebrobasilar junction, bilateral vertebral arteries, and the ipsilateral anterior and posterior inferior cerebellar arteries. At completion, the temporomandibular joint is reconstructed with a prosthetic joint utilizing a second incision along the mandible. Conclusions The mandibular fossa approach is a new trajectory to the petroclival region and the anterior pons. It combines the more anterior angle of endoscopic approaches along with the enhanced control of open approaches. Further study is necessary before this approach is used clinically.

Pharmacological Inhibition of Epidermal Growth Factor Receptor Prevents Intracranial Aneurysm Rupture by Reducing Endoplasmic Reticulum Stress.

BACKGROUND: Multiple pathways and factors are involved in the rupture of intracranial aneurysms. The EGFR (epidermal growth factor receptor) has been shown to mediate inflammatory vascular diseases, including atherosclerosis and aortic aneurysm. However, the role of EGFR in mediating intracranial aneurysm rupture and its underlying mechanisms have yet to be determined. Emerging evidence indicates that endoplasmic reticulum (ER) stress might be the link between EGFR activation and the resultant inflammation. ER stress is strongly implicated in inflammation and apoptosis of vascular smooth muscle cells, both of which are key components of the pathophysiology of aneurysm rupture. Therefore, we hypothesized that EGFR activation promotes aneurysmal rupture by inducing ER stress. METHODS: Using a preclinical mouse model of intracranial aneurysm, we examined the potential roles of EGFR and ER stress in developing aneurysmal rupture. RESULTS: Pharmacological inhibition of EGFR markedly decreased the rupture rate of intracranial aneurysms without altering the formation rate. EGFR inhibition also significantly reduced the mRNA (messenger RNA) expression levels of ER-stress markers and inflammatory cytokines in cerebral arteries. Similarly, ER-stress inhibition also significantly decreased the rupture rate. In contrast, ER-stress induction nullified the protective effect of EGFR inhibition on aneurysm rupture. CONCLUSIONS: Our data suggest that EGFR activation is an upstream event that contributes to aneurysm rupture via the induction of ER stress. Pharmacological inhibition of EGFR or downstream ER stress may be a promising therapeutic strategy for preventing aneurysm rupture and subarachnoid hemorrhage.

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.

Assessing views and attitudes toward the use of extended reality and its implications in neurosurgical education: a survey of neurosurgical trainees.

OBJECTIVE: Extended reality (XR) systems, including augmented reality (AR), virtual reality (VR), and mixed reality, have rapidly emerged as new technologies capable of changing the way neurosurgeons prepare for cases. Thus, the authors sought to evaluate the perspectives of neurosurgical trainees on the integration of these technologies into neurosurgical education. METHODS: A 20-question cross-sectional survey was administered to neurosurgical residents and fellows to evaluate perceptions of the use of XR in neurosurgical training. Respondents evaluated each statement using a modified Likert scale (1-5). RESULTS: One hundred sixteen responses were recorded, with 59.5% of participants completing more than 90% of the questions. Approximately 59% of participants reported having institutional access to XR technologies. The majority of XR users (72%) believed it was effective for simulating surgical situations, compared with only 41% for those who did not have access to XR. Most respondents (61%) agreed that XR could become a standard in neurosurgical education and a cost-effective training tool (60%). Creating patient-specific anatomical XR models was considered relatively easy by 56% of respondents. Those with XR access reported finding it easier to create intraoperative models (58%) than those without access. A significant percentage (79%) agreed on the need for technical skill training outside the operating room (OR), especially among those without XR access (82%). There was general agreement (60%) regarding the specific need for XR. XR was perceived as effectively simulating stress in the OR. Regarding clinical outcomes, 61% believed XR improved efficiency and safety and 48% agreed it enhanced resection margins. Major barriers to XR integration included lack of ample training hours and/or time to use XR amid daily clinical obligations (63%). CONCLUSIONS: The data presented in this study indicate that there is broad agreement among neurosurgical trainees that XR holds potential as a training modality in neurosurgical education. Moreover, trainees who have access to XR technologies tend to hold more positive perceptions regarding the benefits of XR in their training. This finding suggests that the availability of XR resources can positively influence trainees' attitudes and beliefs regarding the utility of these technologies in their education and training.

Vitamin D deficiency promotes intracranial aneurysm rupture.

Intracranial aneurysm rupture causes severe disability and high mortality. Epidemiological studies show a strong association between decreased vitamin D levels and an increase in aneurysm rupture. However, the causality and mechanism remain largely unknown. In this study, we tested whether vitamin D deficiency promotes aneurysm rupture and examined the underlying mechanism for the protective role of vitamin D against the development of aneurysm rupture utilizing a mouse model of intracranial aneurysm. Mice consuming a vitamin D-deficient diet had a higher rupture rate than mice with a regular diet. Vitamin D deficiency increased proinflammatory cytokines in the cerebral arteries. Concurrently, vitamin D receptor knockout mice had a higher rupture rate than the corresponding wild-type littermates. The vitamin D receptors on endothelial and vascular smooth muscle cells, but not on hematopoietic cells, mediated the effect of aneurysm rupture. Our results establish that vitamin D protects against the development of aneurysmal rupture through the vitamin D receptors on vascular endothelial and smooth muscle cells. Vitamin D supplementation may be a viable pharmacologic therapy for preventing aneurysm rupture.

Efficacy of transvenous embolization of CSF-venous fistula in spontaneous intracranial hypotension: Case-series.

BACKGROUND: Spontaneous intracranial hypotension is a debilitating neurological condition which can be caused by a cerebrospinal fluid-venous fistula. Transvenous embolization is a promising technique to provide minimally invasive yet durable treatment. METHODS: A retrospective single-center case series was performed on all patients who underwent transvenous embolization of a cerebrospinal fluid (CSF)-venous fistula. Clinical and radiographic parameters, including Bern score, were reported preoperatively and at 3-month follow-up. RESULTS: Six patients underwent embolization of a CSF-venous fistula. All fistulae were located in the thoracic spine and technical success was achieved in all cases. Three patients had symptom resolution, two had significant improvement, and one had stable symptoms on follow-up. The mean Bern score was 6.83 (SD = 1.47) preoperatively and 1.83 (SD = 1.64) postoperatively with a mean improvement in Bern score of 5.0 (SD = 1.9, p = 0.0013). CONCLUSIONS: CSF-venous fistulas are an increasingly recognized clinical entity which may be treated with transvenous embolization. This case series serves to further validate this technique and suggests it can be performed with similar outcomes in lower volume centers.

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.