Endovascular therapy versus best medical management in distal medium middle cerebral artery acute ischaemic stroke: a multinational multicentre propensity score-matched study.

BACKGROUND: The efficacy of endovascular treatment (EVT) in acute ischaemic stroke due to distal medium vessel occlusion (DMVO) remains uncertain. Our study aimed to evaluate the safety and efficacy of EVT compared with the best medical management (BMM) in DMVO. METHODS: In this prospectively collected, retrospectively reviewed, multicentre cohort study, we analysed data from the Multicentre Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy registry. Patients with acute ischaemic stroke due to DMVO in the M2, M3 and M4 segments who underwent EVT or received BMM were included. Primary outcome measures comprised 10 co-primary endpoints, including functional independence (mRS 0-2), excellent outcome (mRS 0-1), mortality (mRS 6) and haemorrhagic complications. Propensity score matching was employed to balance the cohorts. RESULTS: Among 2125 patients included in the primary analysis, 1713 received EVT and 412 received BMM. After propensity score matching, each group comprised 391 patients. At 90 days, no significant difference was observed in achieving mRS 0-2 between EVT and BMM (adjusted OR 1.00, 95% CI 0.67 to 1.50, p>0.99). However, EVT was associated with higher rates of symptomatic intracerebral haemorrhage (8.4% vs 3.0%, adjusted OR 3.56, 95% CI 1.69 to 7.48, p<0.001) and any intracranial haemorrhage (37% vs 19%, adjusted OR 2.61, 95% CI 1.81 to 3.78, p<0.001). Mortality rates were similar between groups (13% in both, adjusted OR 1.48, 95% CI 0.87 to 2.51, p=0.15). CONCLUSION: Our findings suggest that while EVT does not significantly improve functional outcomes compared with BMM in DMVO, it is associated with higher risks of haemorrhagic complications. These results support a cautious approach to the use of EVT in DMVO and highlight the need for further prospective randomised trials to refine treatment strategies.

Posterior Cerebral Artery Aneurysm Re-Rupture Following Revascularization for Moyamoya Disease.

OBJECTIVES: Aneurysms associated with hemorrhagic moyamoya disease (MMD) are reported to stabilize or recede following revascularization. CASE REPORT/RESULTS: A 29 year-old male with no past medical history presented obtunded with diffuse intraventricular hemorrhage and vascular imaging demonstrating bilateral MMD without any associated aneurysms. He underwent a delayed right-sided STA-MCA bypass and pial synangiosis, and was subsequently discharged on hospital day 24 with a modified Rankin Scale score (mRS) of 2. He returned eleven days later from a rehabilitation facility with recurrent IVH. A saccular 5 mm right P4 segment posterior cerebral artery aneurysm was seen on a diagnostic angiogram and embolized with Onyx glue. CONCLUSIONS: Distal posterior circulation artery aneurysmal rupture is a rare cause of hemorrhagic MMD. This case demonstrates the capacity of these aneurysms to re-rupture following revascularization and underscores the importance of treating the aneurysms directly.

Computed Tomography Angiography Versus Digital Subtraction Angiography for Postclipping Aneurysm Obliteration Detection.

Background and Purpose- Digital subtraction angiography has been used as the gold standard to confirm successful aneurysmal obliteration after aneurysm clipping procedures using titanium or cobalt alloy clips. Computed tomographic angiography is a newer, less invasive imaging technique also used to confirm successful aneurysmal obliteration; however, its use compared with digital subtraction angiography remains controversial. Methods- A comprehensive literature search was conducted on Pubmed, EMBASE, and Cochrane databases through November 6, 2017, for studies that evaluated postclipping aneurysm obliteration with both computed tomographic angiography and digital subtraction angiography. Pooled sensitivity, specificity, positive likelihood ratio (LR+), and negative likelihood ratio (LR-) were calculated using the bivariate random-effects model. Results- Out of 6916 studies, 13 studies met inclusion criteria for this meta-analysis. A total of 510 patients with 613 aneurysms were included. Compared with digital subtraction angiography, which detected 87 residual aneurysms, computed tomographic angiography detected 58 resulting in a pooled sensitivity of 69% (95% CI, 54%-81%) and a pooled specificity of 99% (95% CI, 97%-99%). This corresponded to LR+ of 55.5 (95% CI, 23.6-130.9) and LR- of 0.31 (95% CI, 0.20-0.48). Univariate meta-regression revealed that the pooled sensitivity was worse in prospective designs ( P interaction <0.05), and the pooled specificity was better in higher-quality studies and for postoperative aneurysm diameters of <2 mm ( P interaction <0.001 for both). Conclusions- This meta-analysis revealed that computed tomographic angiography had a favorable LR+ but not a favorable LR-. Thus, this imaging modality may be applicable to rule in, but not rule out, residual aneurysms after clipping.

Interhospital Transfer Before Thrombectomy Is Associated With Delayed Treatment and Worse Outcome in the STRATIS Registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke).

BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (P<0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06-1.79; P=0.02). Likewise, excellent outcome (modified Rankin Score 0-1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13-1.92; P=0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P=0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640.

Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke: Primary Results of the STRATIS Registry.

BACKGROUND AND PURPOSE: Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials. METHODS: STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis. RESULTS: A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab-adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2. CONCLUSIONS: This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.

Outcomes of mechanical thrombectomy in anticoagulated patients with acute distal and medium vessel stroke.

BACKGROUND: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood. METHODS: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, and hemorrhagic complications. RESULTS: Of the patients, 223 (34%) were on anticoagulation therapy. Anticoagulated patients were older (median age 78 vs 74 years; p < 0.001) and had a higher prevalence of atrial fibrillation (77% vs 26%; p < 0.001). Their baseline National Institutes of Health Stroke Scale (NIHSS) scores were also higher (median 12 vs 9; p = 0.002). Before propensity score matching (PSM), anticoagulated patients had similar rates of favorable 90-day outcomes (mRS 0-1: 30% vs 37%, p = 0.1; mRS 0-2: 47% vs 50%, p = 0.41) but higher mortality (26% vs 17%, p = 0.008). After PSM, there were no significant differences in outcomes between the two groups. CONCLUSION: Anticoagulated patients undergoing MT for AIS due to DMVO did not show significant differences in 90-day mRS outcomes, reperfusion, or hemorrhage compared to non-anticoagulated patients after adjustment for covariates.

Pretreatment predictors of very poor clinical outcomes in medium vessel occlusion stroke patients treated with mechanical thrombectomy.

BACKGROUND: Acute ischemic stroke (AIS) from primary medium vessel occlusions (MeVO) is a prevalent condition associated with substantial morbidity and mortality. Despite the common use of mechanical thrombectomy (MT) in AIS, predictors of poor outcomes in MeVO remain poorly characterized. METHODS: In this prospectively collected, retrospectively reviewed, multicenter, multinational study, data from the MAD-MT (Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy) registry were analyzed. The study included 1568 patients from 37 academic centers across North America, Asia, and Europe, treated with MT, with or without intravenous tissue plasminogen activator (IVtPA), between September 2017 and July 2021. RESULTS: Among the 1568 patients, 347 (22.2%) experienced very poor outcomes (modified Rankin score (mRS), 5-6). Key predictors of poor outcomes were advanced age (odds ratio (OR): 1.03; 95% confidence interval (CI): 1.02 to 1.04; p < 0.001), higher baseline National Institutes of Health Stroke Scale (NIHSS) scores (OR: 1.07; 95% CI: 1.05 to 1.10; p < 0.001), pre-operative glucose levels (OR: 1.01; 95% CI: 1.00 to 1.02; p < 0.001), and a baseline mRS of 4 (OR: 2.69; 95% CI: 1.25 to 5.82; p = 0.011). The multivariable model demonstrated good predictive accuracy with an area under the receiver-operating characteristic (ROC) curve of 0.76. CONCLUSIONS: This study demonstrates that advanced age, higher NIHSS scores, elevated pre-stroke mRS, and pre-operative glucose levels significantly predict very poor outcomes in AIS-MeVO patients who received MT. These findings highlight the importance of a comprehensive risk assessment in primary MeVO patients for personalized treatment strategies. However, they also suggest a need for cautious patient selection for endovascular thrombectomy. Further prospective studies are needed to confirm these findings and explore targeted therapeutic interventions.

Predictive value of follow-up infarct volume on functional outcomes in middle cerebral artery M2 segment vessel occlusion stroke treated with mechanical thrombectomy.

BACKGROUND: Medium vessel occlusion (MeVO) strokes, particularly affecting the M2 segment of the middle cerebral artery, represent a critical proportion of acute ischemic strokes, posing significant challenges in management and outcome prediction. The efficacy of mechanical thrombectomy (MT) in MeVO stroke may warrant reliable predictors of functional outcomes. This study aimed to investigate the prognostic value of follow-up infarct volume (FIV) for predicting 90-day functional outcomes in MeVO stroke patients undergoing MT. METHODS: This multicenter, retrospective cohort study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, covering patients with acute ischemic stroke due to M2 segment occlusion treated with MT. We examined the relationship between 90-day functional outcomes, measured by the modified Rankin Scale (mRS), and follow-up infarct volume (FIV), assessed through CT or MRI within 12-36 h post-MT. RESULTS: Among 130 participants, specific FIV thresholds were identified with high specificity and sensitivity for predicting outcomes. A FIV ⩽5 ml was highly specific for predicting favorable and excellent outcomes. The optimal cut-off for both prognostications was identified at ⩽15 ml by the Youden Index, with significant reductions in the likelihood of favorable outcomes observed above a 40 ml threshold. Receiver Operator Curve (ROC) analyses confirmed FIV as a superior predictor of functional outcomes compared to traditional recanalization scores, such as final modified thrombolysis in cerebral infarction score (mTICI). Multivariable analysis further highlighted the inverse relationship between FIV and positive functional outcomes. CONCLUSIONS: FIV within 36 h post-MT serves as a potent predictor of 90-day functional outcomes in patients with M2 segment MeVO strokes. Establishing FIV thresholds may aid in the prognostication of stroke outcomes, suggesting a role for FIV in guiding post intervention treatment decisions and informing clinical practice. Future research should focus on validating these findings across diverse patient populations and exploring the integration of FIV measurements with other clinical and imaging markers to enhance outcome prediction accuracy.

Mechanical Thrombectomy Versus Intravenous Thrombolysis in Distal Medium Vessel Acute Ischemic Stroke: A Multinational Multicenter Propensity Score-Matched Study.

Background and Purpose: The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods: This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results: The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0-1 and 0-2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P<0.001). Conclusion: The results of this study indicate that while MT-IVT and IVT alone show similar functional and mortality outcomes in DMVO patients, MT-IVT presents a higher risk of hemorrhagic complications, thus MT-IVT may not routinely offer additional benefits over IVT alone for all DMVO stroke patients. Further prospective randomized trials are needed to identify patient subgroups most likely to benefit from MT-IVT treatment in DMVO.

Symptomatic intracerebral hemorrhage in proximal and distal medium middle cerebral artery occlusion patients treated with mechanical thrombectomy.

BACKGROUND: Acute ischemic stroke (AIS) caused by distal medium vessel occlusions (DMVOs) represents a significant proportion of overall stroke cases. While intravenous thrombolysis (IVT) has been a primary treatment, advancements in endovascular procedures have led to increased use of mechanical thrombectomy (MT) in DMVO stroke patients. However, symptomatic intracerebral hemorrhage (sICH) remains a critical complication of AIS, particularly after undergoing intervention. This study aims to identify factors associated with sICH in DMVO stroke patients undergoing MT. METHODS: This retrospective analysis utilized data from the Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. Middle cerebral artery (MCA) DMVO stroke patients were included. The primary outcome measured was sICH, as defined per the Heidelberg Bleeding Classification. Univariable and multivariable logistic regression were used to identify factors independently associated with sICH. RESULTS: Among 1708 DMVO stroke patients, 148 (8.7%) developed sICH. Factors associated with sICH in DMVO patients treated with MT included older age (adjusted odds ratio (aOR) 1.01, 95% confidence interval (95% CI) 1.00 to 1.03, P=0.048), distal occlusion site (M3, M4) compared with medium occlusions (M2) (aOR 1.71, 95% CI 1.07 to 2.74, P=0.026), prior use of antiplatelet drugs (aOR 2.06, 95% CI 1.41 to 2.99, P<0.001), lower Alberta Stroke Program Early CT Scores (ASPECTS) (aOR 0.75, 95% CI 0.66 to 0.84, P<0.001), higher preoperative blood glucose level (aOR 1.00, 95% CI 1.00 to 1.01, P=0.012), number of passes (aOR 1.27, 95% CI 1.15 to 1.39, P<0.001), and successful recanalization (Thrombolysis In Cerebral Infarction (TICI) 2b-3) (aOR 0.43, 95% CI 0.28 to 0.66, P<0.001). CONCLUSION: This study provides novel insight into factors associated with sICH in patients undergoing MT for DMVO, emphasizing the importance of age, distal occlusion site, prior use of antiplatelet drugs, lower ASPECTS, higher preoperative blood glucose level, and procedural factors such as the number of passes and successful recanalization. Pending confirmation, consideration of these factors may improve personalized treatment strategies.

The Current State of Neurosurgery in Afghanistan.

BACKGROUND: Afghanistan has suffered through conflicts that have detrimentally impacted its health care systems. The countries' neurosurgeons have worked through wars and political upheavals to build solid practices and handle large caseloads with minimal supplies and almost no modern tools. Understanding the current state of neurosurgery in Afghanistan and the challenges faced by Afghan physicians and patients is critical to improving the country's healthcare capacity. METHODS: To assess neurosurgery research in Afghanistan, searches were conducted in databases for articles originating from Afghanistan neurosurgeons and/or neurosurgery departments. We developed a 30-question English-language survey to assess the current state of neurosurgical capacity. Surveys were distributed to neurosurgeons throughout Afghanistan via email with the assistance of our English-speaking Afghan neurosurgical colleagues. RESULTS: The neurosurgical disease burden of Afghanistan is poorly understood due to the lack of centralized and accessible databases. There are an estimated 124 neurosurgeons in the country based on modeled data. Surveys showed that government hospitals are poorly equipped, with private and military hospitals having access to slightly more modernized equipment but less accessible to the general population. The country lacks neurosurgery research with only 15 papers discovered through database searches deemed relevant to neurosurgery with Afghan affiliations. CONCLUSIONS: Afghanistan is facing existential humanitarian threats. Developing the country's neurosurgical capacity and general health care capabilities is crucial. Emphasis on training physicians and establishing communication routes, and aid deliverance with the country and its leaders is key to overcoming the many crises it faces.

Effects of the COVID-19 pandemic on stroke response times: a systematic review and meta-analysis.

OBJECTIVES: COVID-19 presents a risk for delays to stroke treatment. We examined how COVID-19 affected stroke response times. METHODS: A literature search was conducted to identify articles covering stroke during COVID-19 that included time metrics data pre- and post-pandemic. For each outcome, pooled relative change from baseline and 95% CI were calculated using random-effects models. Heterogeneity was explored through subgroup analyses comparing comprehensive stroke centers (CSCs) to non-CSCs. RESULTS: 38 included studies reported on 6109 patients during COVID-19 and 14 637 patients during the pre-COVID period. Pooled increases of 20.9% (95% CI 5.8% to 36.1%) in last-known-well (LKW) to arrival times, 1.2% (-2.9% to 5.3%) in door-to-imaging (DTI), 0.8% (-2.9% to 4.5%) in door-to-needle (DTN), 2.8% (-5.0% to 10.6%) in door-to-groin (DTG), and 19.7% (11.1% to 28.2%) in door-to-reperfusion (DTR) times were observed during COVID-19. At CSCs, LKW increased by 24.0% (-0.3% to 48.2%), DTI increased by 1.6% (-3.0% to 6.1%), DTN increased by 3.6% (1.2% to 6.0%), DTG increased by 4.6% (-5.9% to 15.1%), and DTR increased by 21.2% (12.3% to 30.1%). At non-CSCs, LKW increased by 12.4% (-1.0% to 25.7%), DTI increased by 0.2% (-2.0% to 2.4%), DTN decreased by -4.6% (-11.9% to 2.7%), DTG decreased by -0.6% (-8.3% to 7.1%), and DTR increased by 0.5% (-31.0% to 32.0%). The increases during COVID-19 in LKW (p=0.01) and DTR (p=0.00) were statistically significant, as was the difference in DTN delays between CSCs and non-CSCs (p=0.04). CONCLUSIONS: Factors during COVID-19 resulted in significantly delayed LKW and DTR, and mild delays in DTI, DTN, and DTG. CSCs experience more pronounced delays than non-CSCs.

Seizure Outcomes After Interventional Treatment in Cerebral Arteriovenous Malformation-Associated Epilepsy: A Systematic Review and Meta-Analysis.

BACKGROUND: Seizures are the second most common presenting symptom of cerebral arteriovenous malformations (AVMs). Evidence supporting different treatment modalities is continuously evolving and it remains unclear which modality offers better seizure outcomes. OBJECTIVE: To compare various interventional treatment modalities (i.e., microsurgery, radiosurgery, endovascular embolization, or multimodality treatment), regarding outcomes in AVM-associated epilepsy. METHODS: PubMed, Embase, and Web of Science were searched on December 31, 2020 for studies that evaluated outcomes in patients with AVM-associated epilepsy after undergoing different treatment modalities. Pooled analysis was performed using a random-effects model and stratified by different modalities. RESULTS: Forty-nine studies including 2668 patients were included. Interventional management was associated with a 56.0% probability of seizure freedom and a 73.0% probability of seizure improvement. The probability of discontinuing antiepileptic drugs was estimated at 38.0%. The stratified analysis showed that microsurgery was associated with a higher probability of seizure freedom and seizure improvement than was radiosurgery, endovascular, or multimodality treatment. The probability of antiepileptic drug cessation was also higher after microsurgery compared with radiation therapy; however, only clinical but not statistical significance could be inferred because of the lack of comparative analyses. CONCLUSIONS: Interventional management of AVM-related epilepsy was associated with seizure freedom and seizure improvement in 56% and 73% of cases. Microsurgery seemed to be associated with a higher incidence of seizure freedom and seizure improvement than did other modalities. Future well-designed comparative studies are needed to draw definitive conclusions regarding each modality.

Somatic Variants in SVIL in Cerebral Aneurysms.

Background and Objectives: While somatic mutations have been well-studied in cancer, their roles in other complex traits are much less understood. Our goal is to identify somatic variants that may contribute to the formation of saccular cerebral aneurysms. Methods: We performed whole-exome sequencing on aneurysm tissues and paired peripheral blood. RNA sequencing and the CRISPR/Cas9 system were then used to perform functional validation of our results. Results: Somatic variants involved in supervillin (SVIL) or its regulation were found in 17% of aneurysm tissues. In the presence of a mutation in the SVIL gene, the expression level of SVIL was downregulated in the aneurysm tissue compared with normal control vessels. Downstream signaling pathways that were induced by knockdown of SVIL via the CRISPR/Cas9 system in vascular smooth muscle cells (vSMCs) were determined by evaluating changes in gene expression and protein kinase phosphorylation. We found that SVIL regulated the phenotypic modulation of vSMCs to the synthetic phenotype via Krüppel-like factor 4 and platelet-derived growth factor and affected cell migration of vSMCs via the RhoA/ROCK pathway. Discussion: We propose that somatic variants form a novel mechanism for the development of cerebral aneurysms. Specifically, somatic variants in SVIL result in the phenotypic modulation of vSMCs, which increases the susceptibility to aneurysm formation. This finding suggests a new avenue for the therapeutic intervention and prevention of cerebral aneurysms.

Concomitant Embolization and Microsurgical Resection of a Giant, Hypervascular Skull Base Meningioma: 2-Dimensional Operative Video.

Some skull base tumors can be extremely hypervascular, incorporating multiple vascular territories and demonstrating arteriovenous shunting. Devascularization is a critical step undertaken early in meningioma surgery, necessary before the debulking that is required in skull base tumors. While devascularization can often be achieved with appropriate approach selection, bony drilling, and microsurgical cautery, preoperative embolization of meningiomas has an invaluable role in selected cases.1,2 Embolization, however, does have added risk, magnified in large tumors by the potential infarction with subsequent edema that can potentially lead to acute deterioration and neurosurgical emergency. Hence, to achieve devascularization of an extremely vascular tumor, embolization and surgical resection should be performed concomitantly, as one operation, in which embolization might be the first stage, or might be performed after the craniotomy flap is raised, if necessary.3 Naturally, this requires the multifaceted neurosurgical expertise of embolization and microsurgical resection, and the facility to perform such. We present a case of a giant, hypervascular, radiation-induced, skull base meningioma with internal and external carotid artery supply in a young patient with deteriorating vision in his only eye. Selective embolization of the internal maxillary, middle meningeal, and middle cerebral artery blood supplies was performed. Microsurgical interruption of the ethmoidal artery blood supply was then performed. This hybrid approach safely and effectively devascularized the tumor and allowed for a complete resection of this high-risk tumor4 while minimizing risk to the ophthalmic artery and optic nerve. The patient was consented for surgery.

Endovascular treatment of a ruptured posterior fossa pure arterial malformation: illustrative case.

BACKGROUND: Pure arterial malformations (PAMs) are rare vascular anomalies that are commonly mistaken for other vascular malformations. Because of their purported benign natural history, PAMs are often conservatively managed. The authors report the case of a ruptured PAM leading to subarachnoid hemorrhage (SAH) with intraventricular extension that was treated endovascularly. OBSERVATIONS: A 38-year-old man presented with a 1-day history of headaches and nausea. A computed tomography scan demonstrated diffuse SAH with intraventricular extension, and angiography revealed a right posterior inferior cerebellar artery-associated PAM. The PAM was treated with endovascular Onyx embolization. LESSONS: To the authors' knowledge, only 2 other cases of SAH associated with PAM have been reported. In those 2 cases, surgical clipping was pursued for definitive treatment. Here, the authors report the first case of a ruptured PAM treated using an endovascular approach, showing its feasibility as a treatment option particularly in patients in whom open surgery is too high a risk.

Safety of the APOLLO Onyx delivery microcatheter for embolization of brain arteriovenous malformations: results from a prospective post-market study.

BACKGROUND: Catheter retention and difficulty in retrieval have been observed during embolization of brain arteriovenous malformations (bAVMs) with the Onyx liquid embolic system (Onyx). The Apollo Onyx delivery microcatheter (Apollo) is a single lumen catheter designed for controlled delivery of Onyx into the neurovasculature, with a detachable distal tip to aid catheter retrieval. This study evaluates the safety of the Apollo for delivery of Onyx during embolization of bAVMs. METHODS: This was a prospective, non-randomized, single-arm, multicenter, post-market study of patients with a bAVM who underwent Onyx embolization with the Apollo between May 2015 and February 2018. The primary endpoint was any catheter-related adverse event (AE) at 30 days, such as unintentional tip detachment or malfunction with clinical sequelae, or retained catheter. Procedure-related AEs (untoward medical occurrence, disease, injury, or clinical signs) and serious AEs (life threatening illness or injury, permanent physiological impairment, hospitalization, or requiring intervention) were also recorded. RESULTS: A total of 112 patients were enrolled (mean age 44.1±17.6 years, 56.3% men), and 201 Apollo devices were used in 142 embolization procedures. The mean Spetzler-Martin grade was 2.38. The primary endpoint was not observed (0/112, 0%). The catheter tip detached during 83 (58.5%) procedures, of which 2 (2.4%) were unintentional and did not result in clinical sequelae. At 30 days, procedure related AEs occurred in 26 (23.2%) patients, and procedure-related serious AEs in 12 (10.7%). At 12 months, there were 3 (2.7%) mortalities, including 2 (1.8%) neurological deaths, none of which were device-related. CONCLUSION: This study demonstrates the safety of Apollo for Onyx embolization of bAVMs. CLINICAL TRIAL REGISTRATION: CNCT02378883.

Comparison of PED and FRED flow diverters for posterior circulation aneurysms: a propensity score matched cohort study.

BACKGROUND: Flow diversion is a common endovascular treatment for cerebral aneurysms, but studies comparing different types of flow diverters are scarce. OBJECTIVE: To perform a propensity score matched cohort study comparing the Pipeline Embolization Device (PED) and Flow Redirection Intraluminal Device (FRED) for posterior circulation aneurysms. METHODS: Consecutive aneurysms of the posterior circulation treated at 25 neurovascular centers with either PED or FRED were collected. Propensity score matching was used to control for age, duration of follow-up imaging, adjunctive coiling, and aneurysm location, size, and morphology; previously ruptured aneurysms were excluded. The two devices were compared for the following outcomes: procedural complications, aneurysm occlusion, and functional outcome. RESULTS: A total of 375 aneurysms of the posterior circulation were treated in 369 patients. The PED was used in 285 (77.2%) and FRED in 84 (22.8%) procedures. Aneurysms treated with the PED were more commonly fusiform and larger than those treated with FRED. To account for these important differences, propensity score matching was performed resulting in 33 PED and FRED unruptured aneurysm pairs. No differences were found in occlusion status and neurologic thromboembolic or hemorrhagic complications between the two devices. The proportion of patients with favorable functional outcome was higher with FRED (100% vs 87.9%, p=0.04). CONCLUSION: Comparative analysis of PED and FRED for the treatment of unruptured posterior circulation aneurysms did not identify significant differences in aneurysm occlusion or neurologic complications. Variations in functional outcomes warrant additional investigations.

Supraselective injection of intraarterial melphalan as the primary treatment for late presentation unilateral multifocal stage Vb retinoblastoma.

PURPOSE: The purpose of this study was to report a case of a 7-year-old girl with unilateral, multifocal Reese Ellsworth Stage Vb retinoblastoma who was successfully treated using intraarterial chemotherapy infusion as the primary therapy. METHODS: This is an interventional case report. A 7-year-old girl presented with advanced unilateral retinoblastoma. The patient received intraarterial melphalan infusion therapy as the primary treatment. RESULTS: Complete tumor resolution was seen at 1 month after intraarterial melphalan infusion. CONCLUSION: This case of advanced retinoblastoma in a 7-year-old girl was successfully treated with intraarterial melphalan infusion alone. Treatment resulted in complete resolution of the tumor 1 month after treatment. In comparison with systemic chemotherapy, intraarterial melphalan infusion therapy may be a less toxic and more effective primary treatment option in the future management of advanced retinoblastoma.

Direct percutaneous embolization of a carotid body tumor with Onyx.

Carotid body tumors (CBTs) are rare highly vascular lesions that frequently require preoperative embolization to minimize surgical morbidity secondary to blood loss. Embolization has typically been performed via a transarterial route. However, this frequently results in incomplete devascularization of the tumor due to the complex angioarchitecture of the feeding arteries. Direct intralesional embolization has been used to gain easier accesses to the tumor vasculature and thus increase the likelihood of complete embolization. Cyanoacrylate glue has been the most commonly used embolic agent. The authors present a case of CBT that underwent direct intralesional embolization using Onyx (ev3; ethylene vinyl alcohol copolymer). To their knowledge, there have been no previous reports of direct percutaneous embolization of a CBT with this agent.