Endothelial Progenitor Cells: A Review of Molecular Mechanisms in the Pathogenesis and Endovascular Treatment of Intracranial Aneurysms.

This comprehensive review explores the multifaceted role of endothelial progenitor cells (EPCs) in vascular diseases, focusing on their involvement in the pathogenesis and their contributions to enhancing the efficacy of endovascular treatments for intracranial aneurysms (IAs). Initially discovered as CD34+ bone marrow-derived cells implicated in angiogenesis, EPCs have been linked to vascular repair, vasculogenesis, and angiogenic microenvironments. The origin and differentiation of EPCs have been subject to debate, challenging the conventional notion of bone marrow origin. Quantification methods, including CD34+ , CD133+ , and various assays, reveal the influence of factors, like age, gender, and comorbidities on EPC levels. Cellular mechanisms highlight the interplay between bone marrow and angiogenic microenvironments, involving growth factors, matrix metalloproteinases, and signaling pathways, such as phosphatidylinositol-3-kinase (PI3K) and mitogen-activated protein kinase (MAPK). In the context of the pathogenesis of IAs, EPCs play a role in maintaining vascular integrity by replacing injured and dysfunctional endothelial cells. Recent research has also suggested the therapeutic potential of EPCs after coil embolization and flow diversion, and this has led the development of device surface modifications aimed to enhance endothelialization. The comprehensive insights underscore the importance of further research on EPCs as both therapeutic targets and biomarkers in IAs.

Embolization Prior to Radiosurgery in Treatment of Arteriovenous Malformations: Defining Radiosurgery Target Dose with Nidal Volume Reduction.

INTRODUCTION: Arteriovenous malformations (AVMs) can be treated with observation, surgery, embolization, stereotactic radiosurgery (SRS), or a combination of therapies. SRS has been used for AVMs that pose a high risk of surgery, such as in deep or eloquent anatomic locations. Smaller AVMs, <3 cm, have been shown to have higher rates of complete obliteration after SRS. For AVMs that are a larger size, embolization prior to SRS has been used to reduce the size of the AVM nidus. In this study we analyzed embolization prior to SRS to reduce nidal volume and describe imaging techniques to target for SRS post embolization. METHODS: We retrospectively reviewed all patients at a single academic institution treated with embolization prior to SRS for treatment of AVMs. We then used contrast enhanced magnetic resonance imaging (MRI) to contour AVM volumes based on pre-embolization imaging and compared to post-embolization imaging. Planned AVM volume prior to embolization was then compared to actual treated AVM volume. RESULTS: We identified 11 patients treated with embolization prior to SRS from 2011-2023. Median AVM nidal volume prior to embolization was 7.69 mL and post embolization was 3.61 ML (P < 0.01). There was a 45.5% obliteration rate at follow up in our series, with 2 minor complications related to radiosurgery. CONCLUSIONS: In our cohort, embolization prior to SRS resulted in a statistically significant reduction in AVM nidal volume. Therefore, embolization prior to SRS can result in dose reduction at time of SRS treatment allowing for decreased risk of SRS complications without higher embolization complication rates.

Defining light transmission aggregometry cutoff values for clopidogrel and aspirin resistance in flow diversion treatment of intracranial aneurysms.

OBJECTIVE: Concern about thromboembolic events after flow diversion (FD) warrants dual antiplatelet therapy for 3 to 6 months. Platelet function tests are routinely performed prior to the procedure to detect clopidogrel responsiveness, as resistance is associated with CYP2C19 gene polymorphisms. This study aimed to identify optimal cutoff values in light transmission aggregometry (LTA) for clopidogrel and aspirin as predictive indicators of thromboembolic complications. METHODS: The authors conducted a retrospective analysis of aneurysms treated with FD between 2013 and 2023 at a single academic institution. Patients with LTA data for adenosine diphosphate (ADP) and arachidonic acid (ARA) were included, excluding those with aborted procedures. Receiver operating characteristic curves were plotted for ADP and ARA assays to determine optimal cutoff values. RESULTS: A total of 442 patients harboring 552 aneurysms treated in 485 procedures were selected for this analysis. Complete and near-complete aneurysm occlusion on the last radiological follow-up was achieved in 81.8% of aneurysms in a median last imaging follow-up of 13.9 months. A good functional outcome (modified Rankin Scale score ≤ 2) was achieved in 96.3% of patients on the last follow-up. Thromboembolic complications occurred in 4.9% of procedures, and intracranial hemorrhagic complications in 1.9%. For the ADP assay, a value ≥ 40% reached a sensitivity of 82.1% and a specificity of 42.9% with a positive likelihood ratio (LR) of 1.50. For the ARA assay, a value ≥ 13.5% reached a sensitivity of 82.1% and a specificity of 45.6% with a positive LR of 1.51. CONCLUSIONS: This study analyzed the largest FD-treated cohort in which optimal LTA platelet function thresholds for clopidogrel were evaluated and is the first to assess LTA values for aspirin. The authors found that values ≥ 40% for clopidogrel and ≥ 13.5% for aspirin were optimal for predicting thromboembolic complications after FD in treating aneurysms.

Thromboembolic Events in the Posterior Circulation After Flow Diversion-A Closer Look at Coverage of the Posterior Cerebral Artery.

BACKGROUND: Flow diversion for bifurcation aneurysms requires excluding one of the branches from the parent artery, raising concern for ischemic events. We evaluated thromboembolic events and their relationship with covering the origin of the posterior cerebral artery (PCA). METHODS: This retrospective analysis included patients with confirmed basilar and proximal PCA aneurysms treated with flow diversion between 2013 and 2023. Procedures were classified according to the coverage of the origin of the PCA. Thromboembolic events associated with the excluded PCA were evaluated. RESULTS: Of the total 28 aneurysms included, 7 were at the basilar tip, 16 in the basilar trunk, and 5 in the first segment of the PCA; 15 were treated by excluding one of the PCAs. Dual antiplatelet therapy included aspirin and ticagrelor (57.1%), aspirin and clopidogrel (35.7%), or aspirin and prasugrel (3.57%). Complete and near-complete aneurysm occlusion was achieved in 80.8% of the aneurysms treated at a median follow-up of 12.31 months. Thromboembolic complications occurred in 3 patients (2 with basilar perforator stroke and 1 with basilar in-stent thrombosis). However, the difference in these events was not statistically significant between patients with PCA coverage and those without (P = 0.46). Diminished flow and a lack of flow was seen in 8 and 7 of the covered vessels, respectively. A modified Rankin scale score of ≤2 was reported for 89.3% of patients at a median clinical follow-up of 5.5 months. CONCLUSIONS: The incidence of thromboembolic events is high in distal basilar and proximal PCA aneurysms; however, PCA coverage was not associated with their occurrence. There was no difference in postprocedural disability between patients whose aneurysms were treated by excluding one of the PCAs and those who were not.

Clipping of a Ruptured Small Anterior Communicating Artery Aneurysm: Technical Video.

In recent years there has been a significant shift in the management of intracranial aneurysms, as most, both ruptured and unruptured, are being treated through an endovascular approach.1-3 However, there are still instances in which open surgical clipping is the best option for definitive management. Both patient factors, such as age and comorbidities, and aneurysm characteristics, such as size, morphology, and location, must be taken into consideration when treating aneurysms. This is especially true for anterior1 communicating artery aneurysms, as these have been treated successfully using multiple different techniques.4,5 There are no absolute guidelines indicating how a particular aneurysm should be treated and, therefore, one must be able to determine how to best manage a patient based on their own skill set, knowledge, and experience. We present a case of a 61-year-old woman who presented with a ruptured anterior communicating artery aneurysm. Initially she was brought to the angiography suite to undergo possible endovascular treatment of the aneurysm, but after reviewing the morphology and size of the aneurysm, we believed that this aneurysm could not be treated safely through an endovascular approach and surgical clipping was the better option. The patient consented to the procedure. In this operative video, we describe the technical aspects of the surgical procedure and the benefits of our approach (Video 1).

Comparison of Thromboembolic Events Between Pipeline Embolization Device (PED) Shield and PED/PED Flex: A Propensity Score-Matched Analysis.

BACKGROUND AND OBJECTIVES: The pipeline embolization device (PED) Flex with Shield technology is a third-generation flow diverter used for intracranial aneurysm treatment designed to decrease thrombogenicity through a phosphorylcholine coating. Herein, we aim to compare the rate of thromboembolic events in PED with Shield technology and PED without it through propensity score matching. METHODS: We conducted a retrospective analysis of aneurysms treated with PED first-generation/PED Flex and PED with Shield between 2013 and 2023 at a single academic institution. Patients were matched through propensity score by controlling for confounding factors including age, smoking history, diabetes, previous subarachnoid hemorrhage, modified Rankin Scale pretreatment, location, aneurysm size, previous treatment, and clopidogrel or aspirin resistance. After matching, we evaluated for periprocedural and postoperative thromboembolic events. Data analysis was performed using Stata 14. RESULTS: A total of 543 patients with 707 aneurysms treated in 605 procedures were included in the analysis. From these, 156 aneurysms were treated with PED with Shield (22.07%) and 551 (77.93%) without Shield technology. Propensity score matching resulted in 84 matched pairs. The rate of thromboembolic events was 3.57% for PED Shield and 10.71% for PED first-generation/PED Flex ( P = .07), while retreatment rates were 2.38% for PED Shield and 8.32% for PED Flex ( P = .09). Complete occlusion at first ( P = .41) and last imaging follow-up ( P = .71), in-stent stenosis ( P = .95), hemorrhagic complications ( P = .31), and functional outcomes ( P = .66) were comparable for both groups. CONCLUSION: This is the first study in the literature performing a propensity scored-matched analysis comparing PED with PED with Shield technology. Our study suggests a trend toward lower thromboembolic events for PED Shield, even after controlling for aspirin and clopidogrel resistance, and a trend toward lower aneurysm retreatment rates with PED Shield, without reaching statistical significance.

Natural history of antiplatelet nonresponders undergoing carotid artery stenting.

OBJECTIVE: Routine antiplatelet responsiveness testing for patients undergoing carotid artery stenting procedures is not performed at most endovascular centers and remains a topic of controversy within the neurointerventional community. The objective of this study was to determine if nonresponsiveness to acetylsalicylic acid or clopidogrel was associated with the development of symptomatic thromboembolic events in patients undergoing carotid stenting procedures. METHODS: A prospective study was conducted at the Foothills Medical Centre in Calgary, Alberta, Canada, from August 2019 to July 2021. Patients undergoing carotid artery stenting procedures and who were receiving dual antiplatelet therapy were enrolled in the study. Responsiveness to the antiplatelet medications was determined through whole blood impedance aggregometry. The primary outcome was development of a symptomatic thromboembolic event within 90 days after the procedure. The treating physicians were blinded to the aggregometry results for the duration of the study. RESULTS: One hundred two procedures were performed in 100 patients. Eight thromboembolic events (8%) occurred during the study. Age (p = 0.03) and nonresponsiveness to clopidogrel (p = 0.003) were associated with the development of thromboembolic events. The multivariable model showed that clopidogrel nonresponsiveness was independently associated with the development of a thromboembolic event (adjusted OR 6.14, 95% CI 1.25-30.11, p = 0.03). CONCLUSIONS: This study demonstrated that patients who were identified as clopidogrel nonresponders, using whole blood impedance aggregometry, were at an increased risk of developing thromboembolic events. Larger studies are needed to assess the utility of routine platelet function testing prior to carotid artery stenting procedures.

A standardized infection prevention bundle for reduction of CSF shunt infections in adult ventriculoperitoneal shunt surgery performed without antibiotic-impregnated catheters.

OBJECTIVE: Ventriculoperitoneal (VP) shunt insertion and revision surgeries are some of the most common procedures that are performed by neurosurgeons. Shunt infections within the adult population are associated with significant morbidity and mortality and rates remain high. The objective of the current study was to use quality improvement (QI) methodology to create a standardized infection prevention bundle aimed at reducing the rate of shunt infections. METHODS: A prospective, single-center, single-surgeon QI study was undertaken. Patients were included if they were 18 years of age or older and were undergoing a VP shunt insertion or revision. The primary outcome of the study was the development of a shunt-related surgical site infection, within 1 year of surgery, as defined according to the Canadian Nosocomial Infection Surveillance Program guidelines. There was no standardized protocol prior to July 2013. A bundle coined as the Calgary Adult Shunt Infection Prevention Protocol (CASIPP) was implemented on July 1, 2013, and updated on July 1, 2015, when 2% chlorhexidine gluconate in 70% isopropyl alcohol replaced povidone-iodine for preoperative skin antisepsis. Protocol compliance was regularly monitored using a standardized process. No antibiotic-impregnated catheters were used. RESULTS: A total of 621 consecutive VP shunt insertions and revisions were included in the study. The rate of shunt infection was 5.8% during the period in which there was no standardized shunt protocol. After the implementation of the CASIPP the infection rate decreased to 4.0%, and after introduction of the chlorhexidine/alcohol skin antisepsis, the infection rate was 0% in 379 consecutive procedures (p < 0.0001). Multivariable logistic regression analysis demonstrated that the use of chlorhexidine/alcohol with CASIPP was associated with a significant reduction in the odds of developing a shunt infection (OR 0.032, 95% CI 0-0.19, p = 0.0005). CONCLUSIONS: The implementation of a standardized shunt infection prevention bundle within the adult population, without the use of antibiotic-impregnated catheters, significantly reduced the rate of shunt infections which was sustained over many years. The use of 2% chlorhexidine gluconate in 70% isopropyl alcohol for preoperative antisepsis may have played a significant role. Multicenter studies should be completed to verify the effectiveness of the authors' protocol.

Clinical outcomes in pediatric hydrocephalus patients treated with endoscopic third ventriculostomy and choroid plexus cauterization: a systematic review and meta-analysis.

OBJECTIVE: Endoscopic third ventriculostomy and choroid plexus cauterization (ETV+CPC) is a novel procedure for infant hydrocephalus that was developed in sub-Saharan Africa to mitigate the risks associated with permanent implanted shunt hardware. This study summarizes the hydrocephalus literature surrounding the ETV+CPC intraoperative abandonment rate, perioperative mortality rate, cerebrospinal fluid infection rate, and failure rate. METHODS: This systematic review and meta-analysis followed a prespecified protocol and abides by Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search strategy using MEDLINE, EMBASE, PsychInfo, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Scopus, and Web of Science was conducted from database inception to October 2019. Studies included controlled trials, cohort studies, and case-control studies of patients with hydrocephalus younger than 18 years of age treated with ETV+CPC. Pooled estimates were calculated using DerSimonian and Laird random-effects modeling, and the significance of subgroup analyses was tested using meta-regression. The quality of the pooled outcomes was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: After screening and reviewing 12,321 citations, the authors found 16 articles that met the inclusion criteria. The pooled estimate for the ETV+CPC failure rate was 0.44 (95% CI 0.37-0.51). Subgroup analysis by geographic income level showed statistical significance (p < 0.01), with lower-middle-income countries having a lower failure rate (0.32, 95% CI 0.28-0.36) than high-income countries (0.53, 95% CI 0.47-0.60). No difference in failure rate was found between hydrocephalus etiology (p = 0.09) or definition of failure (p = 0.24). The pooled estimate for perioperative mortality rate (n = 7 studies) was 0.001 (95% CI 0.00-0.004), the intraoperative abandonment rate (n = 5 studies) was 0.04 (95% CI 0.01-0.08), and the postoperative CSF infection rate (n = 5 studies) was 0.0004 (95% CI 0.00-0.003). All pooled outcomes were found to be low-quality evidence. CONCLUSIONS: This systematic review and meta-analysis provides the most comprehensive pooled estimate for the ETV+CPC failure rate to date and demonstrates, for the first time, a statistically significant difference in failure rate by geographic income level. It also provides the first reported pooled estimates for the risk of ETV+CPC perioperative mortality, intraoperative abandonment, and CSF infection. The low quality of this evidence highlights the need for further research to improve the understanding of these critical clinical outcomes and their relevant explanatory variables and thus to appreciate which patients may benefit most from an ETV+CPC. Systematic review registration no.: CRD42020160149 (https://www.crd.york.ac.uk/prospero/).

Immediate flow-diversion characteristics of a novel primarily bioresorbable flow-diverting stent.

OBJECTIVE: Flow-diverting stents with a resorbable component have significant theoretical benefits over full metal stents, although currently there are none in clinical use. In this study, the authors sought to determine the immediate flow-diversion characteristics of a novel primarily bioresorbable flow-diverting stent. METHODS: Bioresorbable stents were deployed into glass tube models to determine porosity and pore density. In vitro flow diversion behavior was evaluated using high frame rate angiography under pulsatile flow conditions in a patient-specific silicone aneurysm model treated with the resorbable stent as well as the Surpass Evolve stent. In vivo flow diversion was characterized by deployment into 20 rabbit saccular aneurysm models, and grading was based on the O'Kelly-Marotta scale and the 4F-flow diversion predictive score. RESULTS: Porosities and pore densities of the bioresorbable stent were in the flow-diverting range for all target vessel diameters. Quantified results of immediate angiography after placement of the bioresorbable stent into a silicone aneurysm model demonstrated greater flow diversion compared to the Evolve stent. Bioresorbable stent placement in saccular aneurysm models resulted in an immediate O'Kelly-Marotta grade of A3 or better and a 4F-flow diversion predictive score of 4 or better in all cases. CONCLUSIONS: The bioresorbable stent has immediate flow-diversion characteristics that are comparable to commercially available metal stents. Longer-term studies are underway to determine the ability of the resorbable fibers to act as a neointimal scaffold and result in long-term aneurysm occlusion.

Optimal Glucose Target After Aneurysmal Subarachnoid Hemorrhage: A Matched Cohort Study.

BACKGROUND: Hyperglycemia has been associated with poor outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). However, there remains debate as to what optimal glucose targets should be in this patient population. OBJECTIVE: To assess whether we could identify an optimal glucose target for patients with aSAH. METHODS: We performed a post hoc analysis of the "clazosentan to overcome neurological ischemia and infarction occurring after subarachnoid hemorrhage" trial data set. Patients had laboratory results drawn daily for the entirety of their intensive care unit stay. Maximum blood glucose levels were assessed for a relationship with unfavorable outcomes using multiple logistic regression analysis. Maximum blood glucose levels were dichotomized based on the Youden index, which identified a maximum level of <9.2 mmol/L as the optimal cut point for prediction of unfavorable outcomes. Nearest neighbor matching was used to assess the relationship between maintaining glucose levels below the cut point and unfavorable functional outcomes (defined as a modified Rankin score of >2 at 3 mo post-aSAH). The matching was performed after calculation of a propensity score based on identified predictors of outcome and glucose levels. RESULTS: Three hundred eighty-nine patients were included in the matched analysis. Propensity scores were balanced on both the covariates and outcomes of interest. There was a significant average treatment effect (-0.143: 95% confidence interval -0.267 to -0.019) for patients who maintained glucose levels <9.2 mmol/L. CONCLUSION: Maintaining glucose levels below the identified cut point was associated with a decreased risk for unfavorable outcomes in this retrospective matched study.

Intra-arterial injection of mesenchymal stem cells to accelerate neointima formation after endovascular stenting in a rabbit model.

OBJECTIVE: Delayed neointima formation over a neurovascular stent is associated with thrombotic complications that can lead to stroke. The purpose of this study was to evaluate whether an intra-arterial injection of mesenchymal stem cells (MSCs) after stent placement leads to improved neointima and reduced thrombus formation over the device. METHODS: Solitaire stents were placed into the aortas of rabbits that were divided into MSC and control groups. The MSC group received an intra-arterial injection of MSCs through the same microcatheter used for stent deployment. Optical coherence tomography (OCT) was used to evaluate and compare neointima and thrombus formation in a blinded fashion. Explanted specimens were also imaged with scanning electron microscopy (SEM) and evaluated by observers blinded to group allocation using an endothelialization scoring system. RESULTS: The 3-day MSC group was similar to the 7-day controls in terms of stent strut coverage ratio and maximum neointimal thickness, but these values were significantly higher than the 3-day control group based on a hierarchical mixed-effects linear regression analysis. SEM revealed a significantly higher endothelialization score for the MSC group compared with controls at the same time point. There was no difference in thrombus formation between any of the groups. CONCLUSIONS: The intra-arterial injection of MSCs after endovascular stenting accelerated early neointima formation but had no effect on thrombus formation in this study. Larger studies are required to verify these findings and determine the durability and mechanism of this effect.

Reducing the risks of proximal and distal shunt failure in adult hydrocephalus: a shunt outcomes quality improvement study.

OBJECTIVE: Patient outcomes of ventriculoperitoneal (VP) shunt surgery, the mainstay treatment for hydrocephalus in adults, are poor because of high shunt failure rates. The use of neuronavigation or laparoscopy can reduce the risks of proximal or distal shunt catheter failure, respectively, but has less independent effect on overall shunt failures. No adult studies to date have combined both approaches in the setting of a shunt infection prevention protocol to reduce shunt failure. The goal of this study was to determine whether combining neuronavigation and laparoscopy with a shunt infection prevention strategy would reduce the incidence of shunt failures in adult hydrocephalic patients. METHODS: Adult patients (age ≥ 18 years) undergoing VP shunt surgery at a tertiary care institution prior to (pre-Shunt Outcomes [ShOut]) and after (post-ShOut) the start of a prospective continuous quality improvement (QI) study were compared. Pre-ShOut patients had their proximal and distal catheters placed under conventional freehand approaches. Post-ShOut patients had their shunts inserted with neuronavigational and laparoscopy assistance in placing the distal catheter in the perihepatic space (falciform technique). A shunt infection reduction protocol had been instituted 1.5 years prior to the start of the QI initiative. The primary outcome of interest was the incidence of shunt failure (including infection) confirmed by standardized criteria indicating shunt revision surgery. RESULTS: There were 244 (115 pre-ShOut and 129 post-ShOut) patients observed over 7 years. With a background of shunt infection prophylaxis, combined neuronavigation and laparoscopy was associated with a reduction in overall shunt failure rates from 37% to 14%, 45% to 22%, and 51% to 29% at 1, 2, and 3 years, respectively (HR 0.44, p < 0.001). Shunt infection rates decreased from 8% in the pre-ShOut group to 0% in the post-ShOut group. There were no proximal catheter failures in the post-ShOut group. The 2-year rates of distal catheter failure were 42% versus 20% in the pre- and post-ShOut groups, respectively (p < 0.001). CONCLUSIONS: Introducing a shunt infection prevention protocol, placing the proximal catheter under neuronavigation, and placing the peritoneal catheter in the perihepatic space by using the falciform technique led to decreased rates of infection, distal shunt failure, and overall shunt failure.

Promoting endothelialization of flow-diverting stents: a review.

Intracranial flow-diverting (FD) stents have revolutionized the treatment of intracranial aneurysms in recent years, but complications resulting from failed endothelialization can still occur. Approaches to promote endothelialization are understudied, but hold promise in mitigating both short- and long-term complications associated with FD stent insertion. The aim of this review is to highlight the various features of and modifications that have been made to FD stents in order to expedite endothelialization. More specifically, we focus on how endothelialization can be influenced by the stent design, wall apposition, surface modifications, and the inclusion of biological agents.

A Novel Parameter to Predict Supraclinoid Aneurysm Persistence After Flow Diversion with the Pipeline Embolization Device.

BACKGROUND: Aneurysm recurrence after Pipeline Embolization Device (PED) placement can be caused by oversizing of the stent as well as poor wall apposition, both of which can lead to elongation. The objective of this study was to assess whether a novel parameter for measuring device elongation based on two-dimensional imaging could be predictive for persistent aneurysm filling after treatment with the PED. METHODS: A retrospective cohort analysis was initially completed on 41 aneurysms from institution A, examining demographic, aneurysmal, and device measurements. Device measurements, including the ratio of the measured length to the nominal length (ML/NL) of the PED, were taken by reviewers blinded to the primary end point, which was aneurysm occlusion status on 6 month catheter angiogram. Findings were then externally validated against 30 aneurysms (supraclinoid only) from institution B. RESULTS: Data from institution A showed 61% complete aneurysm occlusion at 6 months, and were lower for aneurysms in the supraclinoid region. For supraclinoid aneurysms alone, combined data from both institutions showed higher rates of nonocclusion with aneurysm neck size >4 mm (P = 0.008) and a trend toward significance in aneurysms with a branch vessel (P = 0.051). The mean ML/NL ratio was significantly larger in the nonoccluded group compared with the occluded group at both institution A (ratio, 1.37 versus 1.10; P < 0.001) and institution B (ratio, 1.36 vs. 1.11; P = 0.002). CONCLUSIONS: Our data suggest that a novel parameter based on two-dimensional angiography may serve as a rapid technique to measure device elongation and predict occlusion of supraclinoid aneurysms after PED placement.

Cigarette smoking and risk of intracranial aneurysms in middle-aged women.

BACKGROUND AND PURPOSE: We previously reported a single-centre study demonstrating that smoking confers a six-fold increased risk for having an unruptured intracranial aneurysm (UIA) in women aged between 30 and 60 years and this risk was higher if the patient had chronic hypertension. There are no data with greater generalisability evaluating this association. We aimed to validate our previous findings in women from a multicentre study. METHODS: A multicentre case-control study on women aged between 30 and 60 years, that had magnetic resonance angiography (MRA) during the period 2016-2018. Cases were those with an incidental UIA, and these were matched to controls based on age and ethnicity. A multivariable conditional logistic regression was conducted to evaluate smoking status and hypertension differences between cases and controls. RESULTS: From 545 eligible patients, 113 aneurysm patients were matched to 113 controls. The most common reason for imaging was due to chronic headaches in 62.5% of cases and 44.3% of controls. A positive smoking history was encountered in 57.5% of cases and in 37.2% of controls. A multivariable analysis demonstrated a significant association between positive smoking history (OR 3.7, 95%CI 1.61 to 8.50), hypertension (OR 3.16, 95% CI 1.17 to 8.52) and both factors combined with a diagnosis of an incidental UIA (OR 6.9, 95% CI 2.49 to 19.24). CONCLUSIONS: Women aged between 30 and 60 years with a positive smoking history have a four-fold increased risk for having an UIA, and a seven-fold increased risk if they have underlying chronic hypertension. These findings indicate that women aged between 30 and 60 years with a positive smoking history might benefit from a screening recommendation.

Intrathecal Saline Infusion as an Effective Temporizing Measure in the Management of Spontaneous Intracranial Hypotension.

BACKGROUND: Spontaneous intracranial hypotension (SIH) is a rare condition for which no optimal treatment guidelines have been determined. The most common presentation is orthostatic headaches, but patients can present with a variety of symptoms. CASE DESCRIPTION: We present a case of a 34-year-old man who developed progressive orthostatic headaches and bilateral subdural collections. His symptoms along with imaging of his brain and spine were consistent with SIH. Unfortunately, his symptoms continued to progress, and his level of consciousness became affected. The patient did not respond to either conservative management or epidural blood patching. As the result of his worsening condition, a lumbar drain was inserted for the intrathecal infusion of normal saline to prevent tonsillar herniation. Once the infusion was started, his level of consciousness improved. It was discovered that his cerebrospinal fluid leak was due to an osteophyte within his thoracic spine, which was eroding the dura. He underwent a costo-transversectomy with the removal of the osteophyte and repair of the dural defect. The patient had some improvement after this procedure, but he remained more somnolent than expected. On subsequent imaging, it was found that his subdural collections had increased slightly in size and it was decided to drain them. Both collections were released under high pressure, and he went on to make an excellent recovery. CONCLUSIONS: This case demonstrates that an intrathecal saline infusion can be used as an effective temporizing measure in patients with critical symptoms of SIH and it also alerts clinicians that low-pressure subdural collections can progress to subdural collections under high pressure.

Systematic review of health economic studies in cranial neurosurgery.

OBJECTIVE As the cost of health care continues to increase, there is a growing emphasis on evaluating the relative economic value of treatment options to guide resource allocation. The objective of this systematic review was to evaluate the current evidence regarding the cost-effectiveness of cranial neurosurgery procedures. METHODS The authors performed a systematic review of the literature using PubMed, EMBASE, and the Cochrane Library, focusing on themes of economic evaluation and cranial neurosurgery following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Included studies were publications of cost-effectiveness analysis or cost-utility analysis between 1995 and 2017 in which health utility outcomes in life years (LYs), quality-adjusted life years (QALYs), or disability-adjusted life years (DALYs) were used. Three independent reviewers conducted the study appraisal, data abstraction, and quality assessment, with differences resolved by consensus discussion. RESULTS In total, 3485 citations were reviewed, with 53 studies meeting the inclusion criteria. Of those, 34 studies were published in the last 5 years. The most common subspecialty focus was cerebrovascular (32%), followed by neurooncology (26%) and functional neurosurgery (24%). Twenty-eight (53%) studies, using a willingness to pay threshold of US$50,000 per QALY or LY, found a specific surgical treatment to be cost-effective. In addition, there were 11 (21%) studies that found a specific surgical option to be economically dominant (both cost saving and having superior outcome), including endovascular thrombectomy for acute ischemic stroke, epilepsy surgery for drug-refractory epilepsy, and endoscopic pituitary tumor resection. CONCLUSIONS There is an increasing number of cost-effectiveness studies in cranial neurosurgery, especially within the last 5 years. Although there are numerous procedures, such as endovascular thrombectomy for acute ischemic stroke, that have been conclusively proven to be cost-effective, there remain promising interventions in current practice that have yet to meet cost-effectiveness thresholds.

Combined surgical and endovascular approach to treat a carotid cavernous fistula with associated brainstem venous congestion.

Endovascular embolization is the standard approach for management of carotid cavernous fistulas (CCFs) due to the ease of access and reduced level of risk associated with the procedure compared with open surgery. We present here a case of a CCF that eventually led to the development of brainstem venous congestion from perimedullary venous drainage. This fistula was not amenable to endovascular embolization due to lack of either ophthalmic vein or petrosal sinus drainage. Therefore, a craniotomy with direct puncture of the cavernous sinus was performed, followed by coil embolization to completely treat this fistula. This case demonstrates an uncommon progression of venous drainage to Cognard grade V, rare development of symptomatic brainstem venous congestion and a unique method to combine an open surgical approach with endovascular embolization to treat CCFs.