Cerebral artery overexpression of the NMUR1 gene is associated with moyamoya disease: a weighted gene co-expression network analysis.

INTRODUCTION: This study aimed to elucidate mechanisms underlying moyamoya disease (MMD) pathogenesis and to identify potential novel biomarkers. We utilized gene coexpression networks to identify hub genes associated with the disease. METHODS: Twenty-one middle cerebral artery (MCA) samples from MMD patients and 11 MCA control samples were obtained from the Gene Expression Omnibus (GEO) dataset, GSE189993. To discover functional pathways and potential biomarkers, weighted gene coexpression network analysis (WGCNA) was employed. The hub genes identified were re-assessed through differential gene expression analysis (DGEA) via DESeq2 for further reliability verification. An additional 4 samples from the superficial temporal arteries (STA) from MMD patients were obtained from GSE141025 and a subgroup analysis stratified by arterial type (MCA vs. STA) DGEA was performed to assess if the hub genes associated with MMD are expressed significantly greater on the affected arteries compared to healthy ones in MMD. RESULTS: WGCNA revealed a predominant module encompassing 139 hub genes, predominantly associated with the neuroactive ligand-receptor interaction (NLRI) pathway. Of those, 17 genes were validated as significantly differentially expressed. Neuromedin U receptor 1 (NMUR1) and thyrotropin-releasing hormone (TRH) were 2 out of the 17 hub genes involved in the NLRI pathway (log fold change [logFC]: 1.150, p = 0.00028; logFC: 1.146, p = 0.00115, respectively). MMD-only subgroup analysis stratified by location showed that NMUR1 is significantly overexpressed in the MCA compared to the STA (logFC: 1.962; p = 0.00053) which further suggests its possible localized involvement in the progressive stenosis seen in the cerebral arteries in MMD. CONCLUSION: This is the first study to have performed WGCNA on samples directly affected by MMD. NMUR1 expression is well known to induce localized arterial smooth muscle constriction and recently, type 2 inflammation which can predispose to arterial stenosis potentially advancing the symptoms and progression of MMD. Further validation and functional studies are necessary to understand the precise role of NMUR1 upregulation in MMD and its potential implications.

Cost-effectiveness of platelet function testing in dual antiplatelet therapy decision-making after intracranial aneurysm treatment with flow diversion.

Dual antiplatelet therapy (DAPT) use is the standard of practice after flow diversion (FD) for intracranial aneurysms (IAs). Yet, no consensus exists in the literature regarding the optimal regimen. Certain institutions utilize various platelet function testing (PFT) to assess patient responsiveness to DAPT. Clopidogrel is the most commonly prescribed drug during DAPT; however, up to 52% of patients can be non-responders, justifying PFT use. Additionally, prices vary significantly among antiplatelet drugs, often further complicated by insurance restrictions. We aimed to determine the most cost-effective strategy for deciding DAPT regimens for patients after IA treatment. A decision tree with Monte Carlo simulations was performed to simulate patients undergoing various three-month postoperative DAPT regimens. Patients were either universally administered aspirin alongside clopidogrel, ticagrelor, or prasugrel without PFT, or administered one of the former thienopyridine medications based on platelet reactivity unit (PRU) results after clopidogrel. Input data for the model were extracted from the current literature, and the willingness-to-pay threshold (WTP) was defined as $100,000 per QALY as per standard practice in the US. The baseline comparison was with universal clopidogrel DAPT without any PFT. Probabilistic and deterministic sensitivity analyses were performed to evaluate the robustness of the model. Utilizing PFT and switching clopidogrel to prasugrel if resistance is documented was the most cost-effective regimen compared to universal clopidogrel, with a base-case incremental cost-effectiveness ratio (ICER) of $-35,255 (cost $2,336.67, effectiveness 0.85). Performing PFT and switching clopidogrel to ticagrelor (ICER $-4,671; cost $2,995.06, effectiveness 0.84), universal prasugrel (ICER $5,553; cost $3,097.30, effectiveness 0.84), or universal ticagrelor (ICER $75,969; cost $3,801.36, effectiveness 0.84) were all more cost-effective than treating patients with universal clopidogrel (cost $3,041.77, effectiveness 0.83). These conclusions remain robust in probabilistic and deterministic sensitivity analyses. The most cost-effective strategy guiding DAPT after FD for IAs is to perform PFTs and switch clopidogrel to prasugrel if resistance is documented, alongside aspirin. The cost of PFT is strongly justified and recommended when deciding patient-specific DAPT regimens.

Association between cervicocerebral artery dissection and tortuosity - a review on quantitative and qualitative assessment.

Cervicocerebral artery dissection stands out as a significant contributor to ischemic stroke in young adults. Several studies have shown that arterial tortuosity is associated with dissection. We searched Pubmed and Embase to identify studies on the association between arterial tortuosity and cervicocerebral artery dissection, and to perform a review on the epidemiology of cervicocerebral artery tortuosity and dissection, pathophysiology, measurement of vessels tortuosity, strength of association between tortuosity and dissection, clinical manifestation and management strategies. The prevalence of tortuosity in dissected cervical arteries was reported to be around 22%-65% while it is only around 8%-22% in non-dissected arteries. In tortuous cervical arteries elastin and tunica media degradation, increased wall stiffness, changes in hemodynamics as well as arterial wall inflammation might be associated with dissection. Arterial tortuosity index and vertebrobasilar artery deviation is used to measure the level of vessel tortuosity. Studies have shown an independent association between these two measurements and cervicocerebral artery dissection. Different anatomical variants of tortuosity such as loops, coils and kinks may have a different level of association with cervicocerebral artery dissection. Symptomatic patients with extracranial cervical artery dissection are often treated with anticoagulant or antiplatelet agents, while patients with intracranial arterial dissection were often treated with antiplatelets only due to concerns of developing subarachnoid hemorrhage. Patients with recurrent ischemia, compromised cerebral blood flow or contraindications for antithrombotic agents are usually treated with open surgery or endovascular technique. Those with subarachnoid hemorrhage and intracranial artery dissection are often managed with surgical intervention due to high risk of re-hemorrhage.

Complications of Endovascular and Open Aneurysm Surgery in the Era of Flow Diversion.

The techniques used for treatment of intracranial aneurysms have progressed dramatically over the decades. The introduction of modern endovascular techniques and the continued refinement of progressively less invasive neurosurgical approaches have contributed to steadily improving clinical outcomes. Moreover, innovations such as flow-diverting stents have achieved dramatic success and have gained rapid widespread adoption. Particularly in lesions for which the application of conventional treatment techniques is difficult, flow diversion technology has revolutionized aneurysm management. This review provides a discussion on the morbidity and mortality encountered in the treatment of intracranial aneurysms in the modern era. Common adverse events faced in the management of these lesions with open surgery and various endovascular techniques are highlighted.

Preclinical and clinical role of interleukin-6 in the development of delayed cerebral vasospasm and neuronal cell death after subarachnoid hemorrhage: towards a potential target therapy?

Delayed cerebral vasospasm (DCVS), early brain injury (EBI), and delayed cerebral ischemia (DCI) are devastating complications after aneurysmal subarachnoid hemorrhage (SAH). Interleukin (IL)-6 seems to be an important interleukin in the inflammatory response after SAH, and many studies describe a strong correlation between IL-6 and worse outcome. The aim of this study was to systematically review preclinical and clinical studies that evaluated systemic and cerebral IL-6 levels after SAH and their relation to DCVS, neuronal cell death, and DCI. We conducted two systematic literature searches using PubMed to identify preclinical and clinical studies evaluating the role of IL-6 after SAH. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 61 and 30 preclinical and clinical articles, respectively, were included in the systematic reviews. Of the preclinical studies in which IL-6 was measured in cerebrospinal fluid (CSF), parenchyma, and systemically, 100%, 94.4%, and 81.3%, respectively, showed increased expression of IL-6 after SAH. Preclinical results were mirrored by clinical findings in which elevated levels of IL-6 in CSF and plasma were found after SAH, correlating with DCVS, DCI, and worse outcome. Only two preclinical studies analyzed the direct inhibition of IL-6, which resulted in reduced DCVS and neuronal cell death. IL-6 is a marker of intracranial inflammation and plays a role in the pathophysiology of DCVS and DCI after SAH in preclinical animal models and clinical studies. Its inhibition might have therapeutic potential to improve the outcome of SAH patients.

Early Experience with Comaneci, a Newly FDA-Approved Controllable Assist Device for Wide-Necked Intracranial Aneurysm Coiling.

BACKGROUND: Comaneci (Rapid Medical) is a compliant, adjustable mesh that provides temporary scaffolding during coiling of wide-necked intracranial aneurysms (WNAs) that preserves antegrade flow. We report our early multi-institutional experience with the Comaneci device in the USA. METHOD: We reviewed all patients with WNAs that were treated using the Comaneci device for coil remodeling of ruptured and unruptured aneurysms at 4 institutions between July 2019 and May 2020. Clinical characteristics, angiographic variables, and endovascular results were assessed. RESULTS: A total of 26 patients were included (18 women). The mean age was 62.7 years (range 44-81). Fifteen patients presented with ruptured aneurysms and 11 with unruptured aneurysms. The mean aneurysm neck width was 3.91 mm (range 1.9-6.5) with a mean dome-to-neck ratio of 1.57 (range 0.59-3.39). The mean maximum width was 5.80 mm (range 3.0-9.9) and the mean maximum height was 5.61 mm (range 2.0-11.8). Successful aneurysm occlusion was achieved in 25 of 26 patients. Complete occlusion was achieved in 16 patients, near-complete occlusion was observed in 9 patients, and 1 patient demonstrated residual filling. The mean time of device exposure was 24 min (range 8-76). No vasospasm was observed at the device location. Clot formation on the device was noted in 2 separate cases, but there were no clinical sequelae. There was 1 intraprocedural complication in a case that involved the simultaneous use of 2 Comaneci devices. CONCLUSIONS: Our initial experience shows that the Comaneci device is a promising and reliable tool that can safely support coil remodeling of WNAs.

Investigating the "Weekend Effect" on Outcomes of Patients Undergoing Endovascular Mechanical Thrombectomy for Ischemic Stroke.

OBJECTIVES: With growing evidence of its efficacy for patients with large-vessel occlusion (LVO) ischemic stroke, the use of endovascular thrombectomy (EVT) has increased. The "weekend effect," whereby patients presenting during weekends/off hours have worse clinical outcomes than those presenting during normal working hours, is a critical area of study in acute ischemic stroke (AIS). Our objective was to evaluate whether a "weekend effect" exists in patients undergoing EVT. METHODS: This retrospective, cross-sectional analysis of the 2016-2018 Nationwide Inpatient Sample data included patients ≥18 years with documented diagnosis of ischemic stroke (ICD-10 codes I63, I64, and H34.1), procedural code for EVT, and National Institutes of Health Stroke Scale (NIHSS) score; the exposure variable was weekend vs. weekday treatment. The primary outcome was in-hospital death; secondary outcomes were favorable discharge, extended hospital stay (LOS), and cost. Logistic regression models were constructed to determine predictors for outcomes. RESULTS: We identified 6052 AIS patients who received EVT (mean age 68.7±14.8 years; 50.8% female; 70.8% White; median (IQR) admission NIHSS 16 (10-21). The primary outcome of in-hospital death occurred in 560 (11.1%); the secondary outcome of favorable discharge occurred in 1039 (20.6%). The mean LOS was 7.8±8.6 days. There were no significant differences in the outcomes or cost based on admission timing. In the mixed-effects models, we found no effect of weekend vs. weekday admission on in-hospital death, favorable discharge, or extended LOS. CONCLUSION: These results demonstrate that the "weekend effect" does not impact outcomes or cost for patients who undergo EVT for LVO.

End-of-Treatment Intracerebral and Ventricular Hemorrhage Volume Predicts Outcome: A Secondary Analysis of MISTIE III.

Background and Purpose- Trials have shown potential clinical benefit for minimally invasive clot evacuation of intracerebral hemorrhage (ICH). Prior research showing an association between ICH size and functional outcome did not fully address the spectrum of hematoma volumes seen after clot evacuation. Methods- In this secondary analysis of the MISTIE III trial (Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation III), we included patients randomized to the surgical arm. The primary outcome was good outcome (modified Rankin Scale score 0-3 at 1 year from study enrollment). The primary predictors were the end-of-treatment (EoT) ICH and intraventricular hemorrhage volumes and an end-of-treatment ICH stratification scale called the EoT ICH volume score. Results- In 246 patients, the end-of-treatment computed tomography was performed an average of 5 days from onset. For patients with good versus poor outcomes, the mean end-of-treatment ICH and intraventricular hemorrhage volumes were 12.9 versus 18.0 mL (P=0.002) and 0.5 versus 2.3 mL (P<0.001), respectively. The probability of a good outcome decreased from 73% for EoT ICH volume 3 (<5 mL) to 28% for EoT ICH volume 0 (>20 mL; P=0.001). Conclusions- After surgical clot evacuation, both ICH and intraventricular hemorrhage volumes have a strong association with good neurological outcome. The EoT ICH volume score needs independent verification, but such an approach could be used for prognostication and therapeutic planning.

Middle meningeal artery embolization treatment of nonacute subdural hematomas in the elderly: a multiinstitutional experience of 151 cases.

OBJECTIVE: The incidence of already common chronic subdural hematomas (CSDHs) and other nonacute subdural hematomas (NASHs) in the elderly is expected to rise as the population ages over the coming decades. Surgical management is associated with recurrence and exposes elderly patients to perioperative and operative risks. Middle meningeal artery (MMA) embolization offers the potential for a minimally invasive, less morbid treatment in this age group. The clinical and radiographic outcomes after MMA embolization treatment for NASHs have not been adequately described in elderly patients. In this paper, the authors describe the clinical and radiographic outcomes after 151 cases of MMA embolization for NASHs among 121 elderly patients. METHODS: In a retrospective review of a prospectively maintained database across 15 US academic centers, the authors identified patients aged ≥ 65 years who underwent MMA embolization for the treatment of NASHs between November 2017 and February 2020. Patient demographics, comorbidities, clinical and radiographic factors, treatment factors, and clinical outcomes were abstracted. Subgroup analysis was performed comparing elderly (age 65-79 years) and advanced elderly (age > 80 years) patients. RESULTS: MMA embolization was successfully performed in 98% of NASHs (in 148 of 151 cases) in 121 patients. Seventy elderly patients underwent 87 embolization procedures, and 51 advanced elderly patients underwent 64 embolization procedures. Elderly and advanced elderly patients had similar rates of embolization for upfront (46% vs 61%), recurrent (39% vs 33%), and prophylactic (i.e., with concomitant surgical intervention; 15% vs 6%) NASH treatment. Transfemoral access was used in most patients, and the procedure time was approximately 1 hour in both groups. Particle embolization with supplemental coils was most common, used in 51% (44/87) and 44% (28/64) of attempts for the elderly and advanced elderly groups, respectively. NASH thickness decreased significantly from initial thickness to 6 weeks, with additional decrease in thickness observed in both groups at 90 days. At longest follow-up, the treated NASHs had stabilized or improved in 91% and 98% of the elderly and advanced elderly groups, respectively, with > 50% improvement seen in > 60% of patients for each group. Surgical rescue was necessary in 4.6% and 7.8% of cases, and the overall mortality was 8.6% and 3.9% for elderly and advanced elderly patients, respectively. CONCLUSIONS: MMA embolization can be used safely and effectively as an alternative or adjunctive minimally invasive treatment for NASHs in elderly and advanced elderly patients.

Evaluation of disease severity and treatment intensity as cost drivers for ruptured intracranial aneurysms.

BACKGROUND: Previous studies have not evaluated the impact of illness severity and postrupture procedures in the cost of care for intracranial aneurysms. We hypothesize that the severity of aneurysm rupture and the aggressiveness of postrupture interventions play a role in cost. METHODS: The Value Driven Outcomes database was used to assess direct patient cost during the treatment of ruptured intracranial aneurysm with clipping, coiling, and Pipeline flow diverters. RESULTS: One hundred ninety-eight patients (mean age 52.8 ± 14.1 years; 40.0% male) underwent craniotomy (64.6%), coiling (26.7%), or flow diversion (8.6%). Coiling was 1.4× more expensive than clipping (p = .005) and flow diversion was 1.7× more expensive than clipping (p < .001). More severe illness as measured by American Society of Anesthesia, Hunt/Hess, and Fisher scales incurred higher costs than less severe illness (p < .05). Use of a lumbar drain protocol to reduce subarachnoid hemorrhage and use of an external ventricular drain to manage intracranial pressure were associated with reduced (p = .05) and increased (p < .001) total costs, respectively. Patients with severe vasospasm (p < .005), those that received shunts (p < .001), and those who had complications (p < .001) had higher costs. Multivariate analysis showed that procedure type, length of stay, number of angiograms, vasospasm severity, disposition, and year of treatment were independent predictors of cost. CONCLUSIONS: These results show for the first time that disease and vasospasm severity and intensity of treatment directly impact the cost of care for patients with aneurysms in the USA. Strategies to alter these variables may prove important for cost reduction.

Staged transarterial endovascular embolization of a malignant dural arteriovenous fistula using Onyx and n-butyl cyanoacrylate.

Dural arteriovenous fistulae (dAVFs) are vascular anomalies formed by abnormal connections between branches of dural arteries and dural veins or dural venous sinus(es). These pathologic shunts constitute 10%-15% of all intracranial arteriovenous malformations. The hallmark of malignant dAVFs is the presence of cortical venous drainage, a finding that increases the likelihood of nonhemorrhagic neurologic deficit, intracranial hemorrhage, and mortality if left unaddressed. Endovascular approaches have become the primary modality for the treatment of dAVFs. The authors present a case of staged endovascular transarterial embolization of a malignant dAVF running parallel to the left transverse sinus in a patient with headaches and pulsatile tinnitus. The fistula was completely treated using Onyx and n-butyl cyanoacrylate.The video can be found here: https://youtu.be/GSAto_wlC3I.

Role of matrix metalloproteinases in the pathogenesis of intracranial aneurysms.

Intracranial aneurysms (IAs) are a result of complex interactions between biochemical and mechanical forces and can lead to significant morbidity if they rupture and cause subarachnoid hemorrhage. This review explores the role of matrix metalloproteinases (MMPs) in the pathogenesis and progression of IAs. In addition to providing a review of the normal function of MMPs, it is intended to explore the interaction between inflammation and abnormal blood flow and the resultant pathological vascular remodeling processes seen in the development and rupture of IAs. Also reviewed is the potential for the use of MMPs as a diagnostic tool for assessment of aneurysm development and progression.

Contemporary endovascular and open aneurysm treatment in the era of flow diversion.

Clinical outcomes have improved considerably over the last decade for patients with ruptured and unruptured aneurysms. Modern endovascular techniques, such as flow diversion, are associated with high aneurysm occlusion rates and have become a popular treatment modality for many types of aneurysms. However, the safety and effectiveness of flow diversion has not yet been established in trials comparing it with traditional aneurysm treatments. Moreover, there are some types of aneurysms that may not be appropriate for endovascular coiling, such as wide-necked aneurysms located at branch points of major vessels, large saccular aneurysms with multiple efferent arteries, dolichoectatic aneurysms, large aneurysms with mass effect, when there are technical complications with endovascular treatment, when patients cannot tolerate or have contraindications to antiplatelet therapy or in the setting of a subarachnoid haemorrhage. For these cases, open cerebrovascular surgery remains important. This review provides a discussion on the current trends and evidence for both flow diversion and open cerebrovascular surgery for complex aneurysms that may not be suitable for coiling. We emphasise a continued important role for surgical treatment in certain situations.

Analysis of cerebrovascular aneurysm treatment cost: retrospective cohort comparison of clipping, coiling, and flow diversion.

OBJECTIVE With the continuous rise of health care costs, hospitals and health care providers must find ways to reduce costs while maintaining high-quality care. Comparing surgical and endovascular treatment of intracranial aneurysms may offer direction in reducing health care costs. The Value-Driven Outcomes (VDO) database at the University of Utah identifies cost drivers and tracks changes over time. In this study, the authors evaluate specific cost drivers for surgical clipping and endovascular management (i.e., coil embolization and flow diversion) of both ruptured and unruptured intracranial aneurysms using the VDO system. METHODS The authors retrospectively reviewed surgical and endovascular treatment of ruptured and unruptured intracranial aneurysms from July 2011 to January 2017. Total cost (as a percentage of each patient's cost to the system), subcategory costs, and potential cost drivers were evaluated and analyzed. RESULTS A total of 514 aneurysms in 469 patients were treated; 273 aneurysms were surgically clipped, 102 were repaired with coiling, and 139 were addressed with flow diverter placements. Middle cerebral artery aneurysms accounted for the largest portion of cases in the clipping group (29.7%), whereas anterior communicating artery aneurysms were most frequently involved in the coiling group (30.4%) and internal carotid artery aneurysms were the majority in the flow diverter group (63.3%). Coiling (mean total cost 0.25% ± 0.20%) had a higher cost than flow diversion (mean 0.20% ± 0.16%) and clipping (mean 0.17 ± 0.14%; p = 0.0001, 1-way ANOVA). Coiling cases cost 1.5 times as much as clipping and flow diversion costs 1.2 times as much as clipping. Facility costs were the most significant contributor to intracranial clipping costs (60.2%), followed by supplies (18.3%). Supplies were the greatest cost contributor to coiling costs (43.2%), followed by facility (40.0%); similarly, supplies were the greatest portion of costs in flow diversion (57.5%), followed by facility (28.5%). Cost differences for aneurysm location, rupture status, American Society of Anesthesiologists (ASA) grade, and discharge disposition could be identified, with variability depending on surgical procedure. A multivariate analysis showed that rupture status, surgical procedure type, ASA status, discharge disposition, and year of surgery all significantly affected cost (p < 0.0001). CONCLUSIONS Facility utilization and supplies constitute the majority of total costs in aneurysm treatment strategies, but significant variation exists depending on surgical approach, rupture status, and patient discharge disposition. Developing and implementing approaches and protocols to improve resource utilization are important in reducing costs while maintaining high-quality patient care.

Novel use of flow diversion for the treatment of aneurysms associated with arteriovenous malformations.

The use of flow-diverting stents for intracranial aneurysms has become more prevalent, and flow diverters are now routinely used beyond their initial scope of approval at the proximal internal carotid artery. Although flow diversion for the treatment of cerebral aneurysms is becoming more commonplace, there have been no reports of its use to treat flow-related cerebral aneurysms associated with arteriovenous malformations (AVMs). The authors report the cases of 2 patients whose AVM-associated aneurysms were managed with flow diversion. A 40-year-old woman presented with a history of headaches that led to the identification of an unruptured Spetzler-Martin Grade V, right parietooccipital AVM associated with 3 aneurysms of the ipsilateral internal carotid artery. Initial attempts at balloon-assisted coil embolization of the aneurysms were unsuccessful. The patient underwent placement of a flow-diverting stent across the diseased vessel; a 6-month follow-up angiogram demonstrated complete occlusion of the aneurysms. In the second case, a 57-year-old man presented with new-onset seizures, and an unruptured Spetzler-Martin Grade V, right frontal AVM associated with an irregular, wide-necked anterior communicating artery aneurysm was identified. The patient underwent placement of a flow-diverting stent, and complete occlusion of the aneurysm was observed on a 7-month follow-up angiogram. These 2 cases illustrate the potential for use of flow diversion as a treatment strategy for feeding artery aneurysms associated with AVMs. Because of the need for dual antiplatelet medications after flow diversion in this patient population, however, this strategy should be used judiciously.

Advanced imaging in acute ischemic stroke.

The evaluation and management of acute ischemic stroke has primarily relied on the use of conventional CT and MRI techniques as well as lumen imaging sequences such as CT angiography (CTA) and MR angiography (MRA). Several newer or less-established imaging modalities, including vessel wall MRI, transcranial Doppler ultrasonography, and 4D CTA and MRA, are being developed to complement conventional CT and MRI techniques. Vessel wall MRI provides high-resolution analysis of both extracranial and intracranial vasculature to help identify previously occult lesions or characteristics of lesions that may portend a worse natural history. Transcranial Doppler ultrasonography can be used in the acute setting as a minimally invasive way of identifying large vessel occlusions or monitoring the response to stroke treatment. It can also be used to assist in the workup for cryptogenic stroke or to diagnose a patent foramen ovale. Four-dimensional CTA and MRA provide a less invasive alternative to digital subtraction angiography to determine the extent of the clot burden and the degree of collateral blood flow in large vessel occlusions. Along with technological advances, these new imaging modalities are improving the diagnosis, workup, and management of acute ischemic stroke- roles that will continue to expand in the future.

Stent technology in ischemic stroke.

Atherosclerotic disease of the cerebral vasculature is a major cause of stroke worldwide. Atherosclerosis that is refractory to best medical management may require revascularization. In these instances, endovascular treatment provides a popular and safe alternative to open surgical techniques. The authors provide an overview of stent technology in the treatment of ischemic stroke, discussing the major studies evaluating stenting for extracranial carotid artery, vertebral artery, and intracranial atherosclerotic disease. The authors describe the commonly used stents with respect to their individual characteristics and technical limitations. Current and future developments in stent technology are also discussed, with areas for further innovation and clinical research.

Flow diversion of tandem cerebral aneurysms: a multi-institutional retrospective study.

OBJECTIVE Flow diversion has proven to be an efficacious means of treating cerebral aneurysms that are refractory to other therapeutic means. Patients with tandem aneurysms treated with flow diversion have been included in larger, previously reported series; however, there are no dedicated reports on using this technique during a single session to treat this unique subset of patients. Therefore, the authors analyzed the outcomes of patients who had undergone single-session flow diversion for the treatment of tandem aneurysms. METHODS The authors conducted a retrospective review of flow diversion with the Pipeline embolization device (PED) for the treatment of tandem aneurysms in a single session at 2 participating medical centers: University of Utah, Salt Lake City, Utah, and Barrow Neurological Institute, Phoenix, Arizona. Patient demographic data, aneurysm characteristics, treatment strategy and results, complications, and follow-up data were collected from the medical record and analyzed. RESULTS Between January 2011 and December 2015, 17 patients (12 female, 5 male) with a total of 38 aneurysms (mean size 4.7 ± 2.7 mm, mean ± SD) were treated. Sixteen patients had aneurysms in the anterior circulation, and 1 patient had tandem aneurysms in the posterior circulation. Twelve patients underwent only placement of a PED, whereas 5 underwent adjunctive coil embolization of at least 1 aneurysm. One PED was used in each of 9 patients, and 2 PEDs were required in each of 8 patients. There were 2 intraprocedural complications; however, in both instances, the patients were asymptomatic at the last follow-up. The follow-up imaging studies were available for 15 patients at a mean of 7 months after treatment (216 days, range 0-540 days). The mean initial Raymond score after treatment was 2.7 ± 0.7, and the mean final score was 1.3 ± 0.7. CONCLUSIONS In this series, the use of flow diversion for the treatment of tandem cerebral aneurysms had an acceptable safety profile, indicating that it should be considered as an effective therapy for this complicated subset of patients. Further prospective studies must be performed before more definitive conclusions can be made.

Platelet testing in flow diversion: a review of the evidence.

OBJECTIVE Although the use of dual antiplatelet therapy with flow diversion is recommended and commonplace, the testing of platelet inhibition is more controversial. METHODS The authors reviewed the medical literature to establish and describe the physiology of platelet adhesion, the pharmacology of antiplatelet medications, and the mechanisms of the available platelet function tests. Additionally, they present a review of the pertinent neurointerventional and interventional cardiology literature. RESULTS Competing reports in the neurointerventional literature argue for and against the use of routine platelet function testing, with adjustments to the dosage or medications based on the results. The interventional cardiology literature has also wrestled with this dilemma after percutaneous coronary interventions, with conflicting reports of the benefits of platelet function testing. CONCLUSIONS Despite its prevalence, the benefits of platelet function testing prior to flow diversion are unproven. This practice will likely remain controversial until the level of evidence improves through more rigorous testing and reporting.

Use of the Pipeline embolization device in the treatment of iatrogenic intracranial vascular injuries: a bi-institutional experience.

OBJECTIVE Flow-diverting devices have been used for the treatment of complex intracranial vascular pathology with success, but the role of these devices in treating iatrogenic intracranial vascular injuries has yet to be clearly defined. Here, the authors report their bi-institutional experience with the use of the Pipeline embolization device (PED) for the treatment of iatrogenic intracranial vascular injuries. METHODS The authors reviewed a retrospective cohort of patients with iatrogenic injuries to the intracranial vasculature that were treated with the PED between 2012 and 2016. Data collection included demographic data, indications for treatment, number and sizes of PEDs used, and immediate and follow-up angiographic and clinical outcomes. RESULTS Four patients with a mean age of 47.5 years (range 18-63 years) underwent PED placement for iatrogenic vessel injuries. In 3 patients, the intracranial internal carotid artery (ICA) was injured during transnasal tumor resection. In 1 patient, a basilar apex injury occurred during endoscopic third ventriculostomy. Three patients had a pseudoaneurysm as a result of vessel injury, and 1 patient had frank ICA laceration and extravasation. All 3 pseudoaneurysms were successfully treated with PED deployment. The ICA laceration was refractory to PED placement, and the vessel was subsequently occluded endovascularly. All 4 patients had a good clinical outcome (modified Rankin Scale score of 0 or 1). CONCLUSIONS The use of the PED is feasible in the management of iatrogenic pseudoaneurysms of the intracranial vasculature. In cases of frank vessel perforation, an alternative strategy such as covered stent placement should be considered. Endovascular or surgical vessel occlusion remains the definitive treatment in cases of refractory hemorrhage.