A review of technological innovations leading to modern endovascular brain aneurysm treatment

Tools and techniques utilized in endovascular brain aneurysm treatment have undergone rapid evolution in recent decades. These technique and device-level innovations have allowed for treatment of highly complex intracranial aneurysms and improved patient outcomes. We review the major innovations within neurointervention that have led to the current state of brain aneurysm treatment

Somatic PDGFRB activating variants in fusiform cerebral aneurysms

The role of somatic genetic variants in the pathogenesis of intracranial-aneurysm formation is unknown. We identified a 23-year-old man with progressive, right-sided intracranial aneurysms, ipsilateral to an impressive cutaneous phenotype. The index individual underwent a series of genetic evaluations for known connective-tissue disorders, but the evaluations were unrevealing. Paired-sample exome sequencing between blood and fibroblasts derived from the diseased areas detected a single novel variant predicted to cause a p.Tyr562Cys (g.149505130T>C [GRCh37/hg19]; c.1685A>G) change within the platelet-derived growth factor receptor β gene (PDGFRB), a juxtamembrane-coding region. Variant-allele fractions ranged from 18.75% to 53.33% within histologically abnormal tissue, suggesting post-zygotic or somatic mosaicism. In an independent cohort of aneurysm specimens, we detected somatic-activating PDGFRB variants in the juxtamembrane domain or the kinase activation loop in 4/6 fusiform aneurysms (and 0/38 saccular aneurysms; Fisher's exact test, p < 0.001). PDGFRB-variant, but not wild-type, patient cells were found to have overactive auto-phosphorylation with downstream activation of ERK, SRC, and AKT. The expression of discovered variants demonstrated non-ligand-dependent auto-phosphorylation, responsive to the kinase inhibitor sunitinib. Somatic gain-of-function variants in PDGFRB are a novel mechanism in the pathophysiology of fusiform cerebral aneurysms and suggest a potential role for targeted therapy with kinase inhibitors

Characterization of the genomic and immunologic diversity of malignant brain tumors through multisector analysis

Despite some success in secondary brain metastases, targeted or immune-based therapies have shown limited efficacy against primary brain malignancies such as glioblastoma (GBM). Although the intratumoral heterogeneity of GBM is implicated in treatment resistance, it remains unclear whether this diversity is observed within brain metastases and to what extent cancer cell-intrinsic heterogeneity sculpts the local immune microenvironment. Here, we profiled the immunogenomic state of 93 spatially distinct regions from 30 malignant brain tumors through whole-exome, RNA, and T-cell receptor sequencing. Our analyses identified differences between primary and secondary malignancies, with gliomas displaying more spatial heterogeneity at the genomic and neoantigen levels. In addition, this spatial diversity was recapitulated in the distribution of T-cell clones in which some gliomas harbored highly expanded but spatially restricted clonotypes. This study defines the immunogenomic landscape across a cohort of malignant brain tumors and contains implications for the design of targeted and immune-based therapies against intracranial malignancies. SIGNIFICANCE: This study describes the impact of spatial heterogeneity on genomic and immunologic characteristics of gliomas and brain metastases. The results suggest that gliomas harbor significantly greater intratumoral heterogeneity of genomic alterations, neoantigens, and T-cell clones than brain metastases, indicating the importance of multisector analysis for clinical or translational studies

Single-cell profiling of human dura and meningioma reveals cellular meningeal landscape and insights into meningioma immune response

BACKGROUND: Recent investigations of the meninges have highlighted the importance of the dura layer in central nervous system immune surveillance beyond a purely structural role. However, our understanding of the meninges largely stems from the use of pre-clinical models rather than human samples. METHODS: Single-cell RNA sequencing of seven non-tumor-associated human dura samples and six primary meningioma tumor samples (4 matched and 2 non-matched) was performed. Cell type identities, gene expression profiles, and T cell receptor expression were analyzed. Copy number variant (CNV) analysis was performed to identify putative tumor cells and analyze intratumoral CNV heterogeneity. Immunohistochemistry and imaging mass cytometry was performed on selected samples to validate protein expression and reveal spatial localization of select protein markers. RESULTS: In this study, we use single-cell RNA sequencing to perform the first characterization of both non-tumor-associated human dura and primary meningioma samples. First, we reveal a complex immune microenvironment in human dura that is transcriptionally distinct from that of meningioma. In addition, we characterize a functionally diverse and heterogenous landscape of non-immune cells including endothelial cells and fibroblasts. Through imaging mass cytometry, we highlight the spatial relationship among immune cell types and vasculature in non-tumor-associated dura. Utilizing T cell receptor sequencing, we show significant TCR overlap between matched dura and meningioma samples. Finally, we report copy number variant heterogeneity within our meningioma samples. CONCLUSIONS: Our comprehensive investigation of both the immune and non-immune cellular landscapes of human dura and meningioma at single-cell resolution builds upon previously published data in murine models and provides new insight into previously uncharacterized roles of human dura

Outcomes of Mechanical Thrombectomy for Patients With Stroke Presenting With Low Alberta Stroke Program Early Computed Tomography Score in the Early and Extended Window

Importance: Limited data are available about the outcomes of mechanical thrombectomy (MT) for real-world patients with stroke presenting with a large core infarct. Objective: To investigate the safety and effectiveness of MT for patients with large vessel occlusion and an Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 2 to 5. Design, setting, and participants: This retrospective cohort study used data from the Stroke Thrombectomy and Aneurysm Registry (STAR), which combines the prospectively maintained databases of 28 thrombectomy-capable stroke centers in the US, Europe, and Asia. The study included 2345 patients presenting with an occlusion in the internal carotid artery or M1 segment of the middle cerebral artery from January 1, 2016, to December 31, 2020. Patients were followed up for 90 days after intervention. The ASPECTS is a 10-point scoring system based on the extent of early ischemic changes on the baseline noncontrasted computed tomography scan, with a score of 10 indicating normal and a score of 0 indicating ischemic changes in all of the regions included in the score. Exposure: All patients underwent MT in one of the included centers. Main outcomes and measures: A multivariable regression model was used to assess factors associated with a favorable 90-day outcome (modified Rankin Scale score of 0-2), including interaction terms between an ASPECTS of 2 to 5 and receiving MT in the extended window (6-24 hours from symptom onset). Results: A total of 2345 patients who underwent MT were included (1175 women [50.1%]; median age, 72 years [IQR, 60-80 years]; 2132 patients [90.9%] had an ASPECTS of ≥6, and 213 patients [9.1%] had an ASPECTS of 2-5). At 90 days, 47 of the 213 patients (22.1%) with an ASPECTS of 2 to 5 had a modified Rankin Scale score of 0 to 2 (25.6% [45 of 176] of patients who underwent successful recanalization [modified Thrombolysis in Cerebral Ischemia score ≥2B] vs 5.4% [2 of 37] of patients who underwent unsuccessful recanalization; P = .007). Having a low ASPECTS (odds ratio, 0.60; 95% CI, 0.38-0.85; P = .002) and presenting in the extended window (odds ratio, 0.69; 95% CI, 0.55-0.88; P = .001) were associated with worse 90-day outcome after controlling for potential confounders, without significant interaction between these 2 factors (P = .64). Conclusions and relevance: In this cohort study, more than 1 in 5 patients presenting with an ASPECTS of 2 to 5 achieved 90-day functional independence after MT. A favorable outcome was nearly 5 times more likely for patients with low ASPECTS who had successful recanalization. The association of a low ASPECTS with 90-day outcomes did not differ for patients presenting in the early vs extended MT window

Are Aneurysms Treated With Balloon-Assisted Coiling and Stent-Assisted Coiling Different? Morphological Analysis of 113 Unruptured Wide-Necked Aneurysms Treated With Adjunctive Devices

Abstract BACKGROUND: In the endovascular treatment of wide-necked unruptured aneurysms, there is controversy over which adjunctive device (stent vs balloon) is appropriate. At the payer level it has been posited that stents and balloons treat the same aneurysms, and, as such, the more expensive stents should not be reimbursed. OBJECTIVE: We challenge this assertion, and instead hypothesize that aneurysms treated with stent assistance are morphologically different than those selected for balloon assistance. METHODS: Retrospective review of unruptured aneurysms treated with an adjunctive device between 2008 and 2010. Morphological analysis was performed on the pretreatment 2-D catheter angiogram. The immediate posttreatment Raymond score was compared with that seen on the 12-month follow-up angiogram. RESULTS: One hundred six unruptured aneurysms were treated with an adjunctive device and followed for a mean of 24.5 months. Morphological analysis revealed a lower dome-to-neck ratio (1.5 vs 1.2) and aspect ratio (1.44 vs 1.16) in the aneurysms treated with stent assistance vs balloon assistance. Of the 15.3% that were worse on follow-up angiography, there was no statistical difference between those treated with a stent vs a balloon (17.1% vs 14.2%). The overall re-treatment rate was 10.2% and was not statistically different between the 2 groups (12.7% vs 5.7%). CONCLUSION: We found that unruptured aneurysms selected for treatment with stent-assisted coiling are morphologically different from those selected for treatment with balloon assistance. Despite the more challenging morphology, Raymond scores and re-treatment rates at 1 year were not statistically different between the 2 groups, suggesting an important role for stents in the treatment of unruptured aneurysms

Abstract 1122‐000154: Effect of Intravenous Thrombolysis on Early Clot Lysis in Large Vessel Occlusion Strokes Undergoing Thrombectomy

Introduction: Intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT) are both standard of care treatments for acute ischemic stroke patients with large vessel occlusion (LVO) who are eligible for one or both treatments. IVT may result in early recanalization in some patients with LVO. The objective of this study is to analyze whether IVT influences pre‐thrombectomy clot lysis in LVO acute ischemic strokes. Methods: We reviewed prospectively collected data for all patients with LVO ischemic strokes who were transferred to the angiography suite with intention to perform EVT at a single comprehensive stroke center between January 2016 to December 2018. We identified subjects who showed partial or complete clot lysis vs no lysis based on the first angiographic picture of the occluded territory at the time of the initial vessel selection. Descriptive statistics were used to summarize demographic and clinical characteristics. We compared key predictor variables between lysis and no lysis groups including baseline variables, effect of IVT, time from IVT to groin puncture, LVO location, final modified treatment in cerebral ischemia (mTICI) score and discharge Modified Rankin Scale (mRS). t‐test or Kruskal‐Wallis test for continuous variables and chi square test or Fisher’s Exact test for categorical variables. Results: Two hundred and fifty‐nine patients were included. Among these patients, 10.8% (28/259) showed partial or complete lysis of the clot vs 89.2% (231/259) with no lysis. Among these patients who showed clot lysis, 16/28 (57.1%) received IVT. The use of IVT did not show differences between both groups (p = 0.18). There were no differences in the baseline characteristics except for gender, which was the only variable significantly associated with clot lysis. Men had 2‐fold higher odds of spontaneous lysis compared to females (OR [95%CI]: 2.39 [1.01, 5.65], p = 0.04). There was significant difference in the final mTICI between both groups (p <0.001). Conclusions: Our study showed that IVT in a modern practice was not associated with pre‐thrombectomy lysis. Some patients had pre‐thrombectomy lysis despite not receiving IVT

Left transradial access for cerebral angiography

IntroductionTransradial access is increasingly used among neurointerventionalists as an alternative to the transfemoral route. Currently available data, building on the interventional cardiology experience, primarily focus on right radial access. However, there are clinical scenarios when left-sided access may be indicated. The purpose of this study was to evaluate the technical feasibility of left transradial access to cerebral angiography across three institutions.MethodsA retrospective chart review was performed for patients who underwent cerebral angiography accessed via the left radial artery at three institutions between January 2018 and July 2019. The outcome variables studied were successful catheterization, vascular complications, and fluoroscopic time.ResultsNineteen patients underwent a total of 25 cerebral angiograms via left transradial access for cerebral aneurysms (n=15), basilar occlusion (n=1), carotid stenosis (n=1), arteriovenous malformation (n=1), and cervical neurofibroma (n=1). There were 12 diagnostic angiograms and 13 interventional angiograms. The left transradial approach was chosen due to left vertebrobasilar pathology (n=22), right subclavian stenosis (n=2), and previous right arm amputation (n=1). There was one instance of radial artery spasm, which resolved after catheter removal, and one conversion to transfemoral access in an interventional case due to lack of distal catheter support. There were no procedural complications.ConclusionsLeft transradial access in diagnostic and interventional cerebral angiography is a technically feasible, safe, and an effective alternative when indicated, and may be preferable for situations in which pathology locations or anatomic limitations preclude right-sided radial access

Transradial approach for flow diversion treatment of cerebral aneurysms: a multicenter study

BackgroundThe transradial approach (TRA) to endovascular procedures decreases access site morbidity and mortality in comparison with the traditional transfemoral technique (TFA). Despite its improved safety profile, there is a concern that TRA is less favorable for neurointerventional procedures that require large coaxial systems to manage the small tortuous cerebral vessels.ObjectiveTo report our experience with TRA for flow diverter placement for treatment of unruptured cerebral aneurysms.MethodsWe performed a retrospective review of prospective institutional databases at two high-volume centers to identify 49 patients who underwent flow diversion for aneurysm treatment via primary TRA between November 2016 and November 2018. Patient demographics, procedural techniques, and clinical data were recorded.ResultsOf the 49 patients, 39 underwent successful flow diversion placement by TRA. Ten patients were converted to TFA after attempted TRA. There were no procedural complications. Reasons for failure included tortuosity in eight patients and severe radial artery spasm in two.ConclusionsIn the largest reported series to date of flow diverter deployment via TRA for aneurysm treatment, we demonstrate the technical feasibility and safety of the method. The most common reason for failure of TRA was an acute angle of left common carotid artery origin or left internal carotid artery tortuosity. Overall, our data suggest that increasing adoption of TRA is merited given its apparent equivalence to the current TFA technique and its documented reduction in access site complications

Feasibility and safety of transradial access for pediatric neurointerventions

BackgroundDiagnostic cerebral angiograms are increasingly being performed by transradial access (TRA) in adults, following data from the coronary literature supporting fewer access-site complications. Despite this ongoing trend in neuroangiography, there has been no discussion of its use in the pediatric population. Pediatric TRA has scarcely been described even for coronary or other applications. This is the first dedicated large study of transradial access for neuroangiography in pediatric patients.MethodsA multi-institutional series of consecutively performed pediatric transradial angiograms and interventions was collected. This included demographic, procedural, outcomes, and safety data. Data was prospectively recorded and retrospectively analyzed.ResultsThirty-seven diagnostic angiograms and 24 interventions were performed in 47 pediatric patients. Mean age, height, and weight was 14.1 years, 158.6 cm, and 57.1 kg, respectively. The radial artery measured 2.09+/-0.54 mm distally, and 2.09+/-0.44 mm proximally. Proximal and distal angiography were performed for both diagnostic and interventional application (17 distal angiograms, two distal interventions). Clinically significant vasospasm occurred in eight patients (13.1%). Re-access was successfully performed 11 times in seven patients. Conversion to femoral access occurred in five cases (8.2%). The only access-related complication was a small asymptomatic wrist hematoma after TR band removal.ConclusionsTransradial access in pediatric patients is safe and feasible. It can be performed successfully in many cases but carries some unique challenges compared with the adult population. Despite the challenge of higher rates of vasospasm and conversion to femoral access, it is worth exploring further, given the potential benefits