Cerebral Venous Thrombosis Associated with COVID-19.

Despite the severity of coronavirus disease 2019 (COVID-19) being more frequently related to acute respiratory distress syndrome and acute cardiac and renal injuries, thromboembolic events have been increasingly reported. We report a unique series of young patients with COVID-19 presenting with cerebral venous system thrombosis. Three patients younger than 41 years of age with confirmed Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) infection had neurologic findings related to cerebral venous thrombosis. They were admitted during the short period of 10 days between March and April 2020 and were managed in an academic institution in a large city. One patient had thrombosis in both the superficial and deep systems; another had involvement of the straight sinus, vein of Galen, and internal cerebral veins; and a third patient had thrombosis of the deep medullary veins. Two patients presented with hemorrhagic venous infarcts. The median time from COVID-19 symptoms to a thrombotic event was 7 days (range, 2-7 days). One patient was diagnosed with new-onset diabetic ketoacidosis, and another one used oral contraceptive pills. Two patients were managed with both hydroxychloroquine and azithromycin; one was treated with lopinavir-ritonavir. All patients had a fatal outcome. Severe and potentially fatal deep cerebral thrombosis may complicate the initial clinical presentation of COVID-19. We urge awareness of this atypical manifestation.

Multicenter Postmarket Analysis of the Neuroform Atlas Stent for Stent-Assisted Coil Embolization of Intracranial Aneurysms.

BACKGROUND AND PURPOSE: The Neuroform Atlas is a new microstent to assist coil embolization of intracranial aneurysms that recently gained FDA approval. We present a postmarket multicenter analysis of the Neuroform Atlas stent. MATERIALS AND METHODS: On the basis of retrospective chart review from 11 academic centers, we analyzed patients treated with the Neuroform Atlas after FDA exemption from January 2018 to June 2019. Clinical and radiologic parameters included patient demographics, aneurysm characteristics, stent parameters, complications, and outcomes at discharge and last follow-up. RESULTS: Overall, 128 aneurysms in 128 patients (median age, 62 years) were treated with 138 stents. Risk factors included smoking (59.4%), multiple aneurysms (27.3%), and family history of aneurysms (16.4%). Most patients were treated electively (93.7%), and 8 (6.3%) underwent treatment within 2 weeks of subarachnoid hemorrhage. Previous aneurysm treatment failure was present in 21% of cases. Wide-neck aneurysms (80.5%), small aneurysm size (<7 mm, 76.6%), and bifurcation aneurysm location (basilar apex, 28.9%; anterior communicating artery, 27.3%; and middle cerebral artery bifurcation, 12.5%) were common. A single stent was used in 92.2% of cases, and a single catheter for both stent placement and coiling was used in 59.4% of cases. Technical complications during stent deployment occurred in 4.7% of cases; symptomatic thromboembolic stroke, in 2.3%; and symptomatic hemorrhage, in 0.8%. Favorable Raymond grades (Raymond-Roy occlusion classification) I and II were achieved in 82.9% at discharge and 89.5% at last follow-up. mRS ≤2 was determined in 96.9% of patients at last follow-up. The immediate Raymond-Roy occlusion classification grade correlated with aneurysm location (P < .0001) and rupture status during treatment (P = .03). CONCLUSIONS: This multicenter analysis provides a real-world safety and efficacy profile for the treatment of intracranial aneurysms with the Neuroform Atlas stent.

Toward Better Understanding of Flow Diversion in Bifurcation Aneurysms.

BACKGROUND AND PURPOSE: Flow diversion is being increasingly used to treat bifurcation aneurysms. Empiric approaches have generally led to encouraging results, and a growing body of animal and ex vivo literature addresses the fate of target aneurysms and covered branches. Our prior investigations highlighted the dynamic nature of metal coverage provided by the Pipeline Embolization Device and suggested strategies for creating optimal single and multidevice constructs. We now address the geometric and hemodynamic aspects of jailing branch vessels and neighboring target aneurysms. MATERIALS AND METHODS: Fundamental electric and fluid dynamics principles were applied to generate equations describing the relationships between changes in flow and the degree of vessel coverage in settings of variable collateral support to the jailed territory. Given the high complexity of baseline and posttreatment fluid dynamics, in vivo, we studied a simplified hypothetic system with minimum assumptions to generate the most conservative outcomes. RESULTS: In the acute setting, Pipeline Embolization Devices modify flow in covered branches, principally dependent on the amount of coverage, the efficiency of collateral support, and intrinsic resistance of the covered parenchymal territory. Up to 30% metal coverage of any branch territory is very likely to be well-tolerated regardless of device or artery size or the availability of immediate collateral support, provided, however, that no acute thrombus forms to further reduce jailed territory perfusion. CONCLUSIONS: Basic hemodynamic principles support the safety of branch coverage during aneurysm treatment with the Pipeline Embolization Device. Rational strategies to build bifurcation constructs are feasible.

Toward a Better Understanding of Dural Arteriovenous Fistula Angioarchitecture: Superselective Transvenous Embolization of a Sigmoid Common Arterial Collector.

BACKGROUND AND PURPOSE: Our aim was to propose a conceptually new angioarchitectural model of some dural arteriovenous fistulas based on subset analysis of transverse and sigmoid type lesions. The "common collector" notion argues for convergence of multiple smaller caliber arterial vessels on a common arterial collector vessel within the sinus wall. Communication of this single collector (or constellation of terminal collectors) with the sinus proper defines the site of arteriovenous fistula, which can be closed by highly targeted embolization, preserving the sinus and avoiding unnecessary permeation of indirect arterial feeders. MATERIALS AND METHODS: One hundred consecutive dural arteriovenous shunts were examined. Thirty-six transverse/sigmoid fistulas were identified within this group and analyzed for the presence of a common arterial collector as well as other parameters, including demographics, grade, treatment approach, and outcome. RESULTS: A common collector was identified in nearly all Cognard type I lesions (15 fistulas with 14 single collector vessels seen) and progressively less frequently in higher grade fistulas. Identification of the common collector requires careful angiographic analysis, including supraselective and intraprocedural angiographies during treatment, and final embolic material morphology. CONCLUSIONS: Detailed evaluation of imaging studies allows frequent identification of a vascular channel in the sinus wall, which we argue reflects a compound, common arterial channel (rather than a venous collector) with 1 or several discrete fistulous points between this vessel and the sinus proper. Targeted closure of this channel is often feasible, with sinus preservation and avoidance of embolic material penetration into arteries remote from fistula site.

Local delivery of a selective androgen receptor modulator failed as an anabolic agent in a rat bone marrow ablation model.

BACKGROUND AND PURPOSE: Selective androgen receptor modulators (SARMs) have been developed to have systemic anabolic effects on bones and muscles without the adverse effects of steroidal androgens. One unexplored therapeutic option is the targeted application of SARMs for the enhancement of local new bone formation. We evaluated the osteogenic efficacy of a locally released SARM (ORM-11984). METHODS: ORM-11984 was mixed with a copolymer of L-lactide and ɛ-caprolactone (PLCL). An in vitro dissolution test confirmed the sustainable release of ORM-11984 from the matrix. A bone marrow ablation model was used in female Sprague-Dawley rats. Implants containing 10%, 30%, or 50% ORM-11984 by weight or pure PLCL were inserted into the medullary canal of the ablated tibia. At 6 and 12 weeks, the volume of intramedullary new bone and the perimeter of bone-implant contact were measured by micro-computed tomography and histomorphometry. RESULTS: Contrary to our hypothesis, there was a negative correlation between the amount of new bone around the implant and the dose of ORM-11984. There was only a mild (and not statistically significant) enhancement of bone formation in ablated bones subjected to the lowest dose of the SARM (10%). INTERPRETATION: This study suggests that intramedullary/endosteal osteogenesis had a negative, dose-dependent response to locally released SARM. This result highlights the complexity of androgenic effects on bones and also suggests that there are biological limits to the targeted local application of SARMs.

Endoluminal Reconstruction for Nonsaccular Aneurysms of the Proximal Posterior Cerebral Artery with the Pipeline Embolization Device.

BACKGROUND AND PURPOSE: Treatment options for nonsaccular posterior cerebral artery aneurysms include a range of surgical and endovascular reconstructive and deconstructive methods. However, no truly satisfactory treatment option is available to date for lesions arising from the P1 and P2 segments. The purpose of the present case series is to investigate both the efficacy and safety of the Pipeline Embolization Device in treating these challenging aneurysms. MATERIALS AND METHODS: We present a series of 6 consecutive patients who underwent endoluminal reconstruction with the Pipeline Embolization Device for nonsaccular P1 or P2 segment aneurysms between January 2009 and June 2013. RESULTS: Aneurysm location included the P1 segment in 2 patients and the P2 segment in 4 patients. Mean aneurysm diameter was 23 mm (range, 5-44 mm). Mean length of the arterial segment involved was 10 mm (range, 6-19 mm). Clinical presentation included mass effect in 4 patients and perforator stroke and subacute aneurysmal subarachnoid hemorrhage in 1 patient each. Endovascular reconstruction was performed by using 1 Pipeline Embolization Device in 5 patients and 2 overlapping Pipeline Embolization Devices in the remaining patient. Angiographic aneurysm occlusion was immediate in 1 patient, within 6 months in 4 patients, and within 1 year in the remaining patient. Index symptoms resolved in 4 patients and stabilized in the remaining 2. No new permanent neurologic sequelae and no aneurysm recurrence were recorded during the mean follow-up period of 613 days (range, 540-725 days). CONCLUSIONS: Endovascular reconstruction with the Pipeline Embolization Device for nonsaccular aneurysms arising from the P1 and P2 segments compares favorably with historical treatment options in terms of occlusion rate, margin of safety, and neurologic outcome.

Anterior choroidal artery patency and clinical follow-up after coverage with the pipeline embolization device.

BACKGROUND AND PURPOSE: Endoluminal reconstruction with the Pipeline Embolization Device is an effective treatment option for select intracranial aneurysms. However, concerns for the patency of eloquent branch arteries covered by the Pipeline Embolization Device have been raised. We aimed to examine the patency of the anterior choroidal artery and clinical sequelae after ICA aneurysm treatment. MATERIALS AND METHODS: We prospectively analyzed all patients among our first 157 patients with ICA aneurysms treated by the Pipeline Embolization Device who required placement of at least 1 device across the ostium of the anterior choroidal artery. The primary outcome measure was angiographic patency of the anterior choroidal artery at last follow-up. Age, sex, type of aneurysm, neurologic examination data, number of Pipeline Embolization Devices used, relationship of the anterior choroidal artery to the aneurysm, and completeness of aneurysm occlusion on follow-up angiograms were also analyzed. RESULTS: Twenty-nine aneurysms requiring placement of at least 1 Pipeline Embolization Device (median = 1, range = 1-3) across the anterior choroidal artery ostium were identified. At angiographic follow-up (mean = 15.1 months; range = 12-39 months), the anterior choroidal artery remained patent, with antegrade flow in 28/29 aneurysms (96.5%), while 24/29 (82.7%) of the target aneurysms were angiographically occluded by 1-year follow-up angiography. Anterior choroidal artery occlusion, with retrograde reconstitution of the vessel, was noted in a single case. A significant correlation between the origin of the anterior choroidal artery from the aneurysm dome and failure of the aneurysms to occlude following treatment was found. CONCLUSIONS: After placement of 36 Pipeline Embolization Devices across 29 anterior choroidal arteries (median = 1 device, range = 1-3 devices), 1 of 29 anterior choroidal arteries was found occluded on angiographic follow-up. The vessel occlusion did not result in persistent clinical sequelae. Coverage of the anterior choroidal artery origin with the Pipeline Embolization Device, hence, may be considered reasonably safe when deemed necessary for aneurysm treatment.

Cavernous carotid aneurysms in the era of flow diversion: a need to revisit treatment paradigms.

BACKGROUND AND PURPOSE: Recent techniques of endoluminal reconstruction with flow-diverting stents have not been incorporated into treatment algorithms for cavernous carotid aneurysms. This study examines the authors' institutional experience and a systematic review of the literature for outcomes and complications using the Pipeline Embolization Device in unruptured cavernous carotid aneurysms. MATERIALS AND METHODS: A retrospective search for cavernous carotid aneurysms from a prospectively collected data base of aneurysms treated with the Pipeline Embolization Device at our institution was performed. Baseline demographic, clinical, and laboratory values; intrainterventional data; and data at all follow-up visits were collected. A systematic review of the literature for complication data was performed with inquiries sent when clarification of data was needed. RESULTS: Forty-three cavernous carotid aneurysms were included in the study. Our mean radiographic follow-up was 2.05 years. On last follow-up, 88.4% of the aneurysms treated had complete or near-complete occlusion. Aneurysm complete or near-complete occlusion rates at 6 months, 12 months, and 36 months were 81.4%, 89.7%, and 100%, respectively. Of patients with neuro-ophthalmologic deficits on presentation, 84.2% had improvement in their visual symptoms. Overall, we had a 0% mortality rate and a 2.3% major neurologic complication rate. Our systematic review of the literature yielded 227 cavernous carotid aneurysms treated with the Pipeline Embolization Device with mortality and morbidity rates of 0.4% and 3.1%, respectively. CONCLUSIONS: Endoluminal reconstruction with flow diversion for large unruptured cavernous carotid aneurysms can yield high efficacy with low complications. Further long-term data will be helpful in assessing the durability of the cure; however, we advocate a revisiting of current management paradigms for cavernous carotid aneurysms.

Toward an endovascular internal carotid artery classification system.

SUMMARY: Does the world need another ICA classification scheme? We believe so. The purpose of proposed angiography-driven classification is to optimize description of the carotid artery from the endovascular perspective. A review of existing, predominantly surgically-driven classifications is performed, and a new scheme, based on the study of NYU aneurysm angiographic and cross-sectional databases is proposed. Seven segments - cervical, petrous, cavernous, paraophthlamic, posterior communicating, choroidal, and terminus - are named. This nomenclature recognizes intrinsic uncertainty in precise angiographic and cross-sectional localization of aneurysms adjacent to the dural rings, regarding all lesions distal to the cavernous segment as potentially intradural. Rather than subdividing various transitional, ophthalmic, and hypophyseal aneurysm subtypes, as necessitated by their varied surgical approaches and risks, the proposed classification emphasizes their common endovascular treatment features, while recognizing that many complex, trans-segmental, and fusiform aneurysms not readily classifiable into presently available, saccular aneurysm-driven schemes, are being increasingly addressed by endovascular means. We believe this classification may find utility in standardizing nomenclature for outcome tracking, treatment trials and physician communication.

Evaluating CT perfusion using outcome measures of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: DCI is a serious complication following aneurysmal SAH and remains a leading cause of morbidity and mortality. Our aim was to evaluate CTP in aneurysmal SAH by using outcome measures of DCI. MATERIALS AND METHODS: This was a retrospective study of consecutive patients with SAH enrolled in a prospective institutional review board-approved clinical accuracy trial. Qualitative CTP deficits were determined by 2 neuroradiologists blinded to clinical and imaging data. Quantitative CTP was performed by using a standardized protocol with region-of-interest placement sampling of the cortex. Primary outcome measures were permanent neurologic deficits and infarction. The secondary outcome measure was DCI, defined as clinical deterioration. CTP test characteristics (95% CI) were determined for each outcome measure. Statistical significance was calculated by using the Fisher exact and Student t tests. ROC curves were generated to determine accuracy and threshold analysis. RESULTS: Ninety-six patients were included. Permanent neurologic deficits developed in 33% (32/96). CTP deficits were seen in 78% (25/32) of those who developed permanent neurologic deficits and 34% (22/64) of those without (P < .0001). CTP deficits had 78% (61%-89%) sensitivity, 66% (53%-76%) specificity, and 53% (39%-67%) positive and 86% (73%-93%) negative predictive values. Infarction occurred in 18% (17/96). CTP deficits were seen in 88% (15/17) of those who developed infarction and 41% (32/79) of those without (P = .0004). CTP deficits had an 88% (66%-97%) sensitivity, 59% (48%-70%) specificity, and 32% (20%-46%) positive and 96% (86%-99%) negative predictive values. DCI was diagnosed in 50% (48/96). CTP deficits were seen in 81% (39/48) of patients with DCI and in 17% (8/48) of those without (P < .0001). CTP deficits had 81% (68%-90%) sensitivity, 83% (70%-91%) specificity, and 83% (70%-91%) positive and 82% (69%-90%) negative predictive values. Quantitative CTP revealed significantly reduced CBF and prolonged MTT for DCI, permanent neurologic deficits, and infarction. ROC analysis showed that CBF and MTT had the highest accuracy. CONCLUSIONS: CTP may add prognostic information regarding DCI and poor outcomes in aneurysmal SAH.

Short-term clinico-radiographic response to super-selective intra-arterial cerebral infusion of Bevacizumab for the treatment of vestibular schwannomas in Neurofibromatosis type 2.

Neurofibromatosis type 2 (NF2) is an autosomal dominant syndrome with a prevalence of approximately 1 in 30,000. NF 2 is characterized by bilateral vestibular schwannomas, as well as meningiomas, ependymomas and gliomas. Currently, surgical resection and radiotherapy represent the mainstay of treatment, although new studies suggest a role for certain chemotherapeutic agents. Intravenous administration of Bevacizumab (Avastin, Genetech Pharmaceuticals) has been shown to be active in the treatment of vestibular schwannomas. The IV route of administration, however, carries a risk of known systemic side-effects such as bowel perforation, wound dehiscence and pulmonary embolism. In addition, the percentage of drug that reaches the tumor site may be restricted by the blood tumor barrier. This report describes the super-selective intra-arterial infusion of Bevacizumab following blood brain barrier disruption for the treatment of vestibular schwannomas in three patients with Neurofibromatosis type 2. It represents the first time such a technique has been performed for this disease. Additionally, this method of drug delivery may have important implications in the treatment of patients with vestibular schwannomas associated with Neurofibromatosis type 2.

Intraprocedural aneurysmal rupture during coil embolization of brain aneurysms: role of balloon-assisted coiling.

BACKGROUND AND PURPOSE: Intraprocedural aneurysmal rupture is a feared complication of coil embolization of intracranial aneurysms and is associated with high rates of morbidity and mortality. We report the incidence, endovascular management, and clinical outcome of patients with IAR, with emphasis on the role of the balloon-assisted technique. MATERIALS AND METHODS: We conducted a retrospective analysis of all intracranial aneurysms treated by coil embolization between September 2001 and June 2011. All patients with IAR were studied. Comparison of immediate clinical outcomes was performed by using univariate analysis (Fisher exact test). RESULTS: Of 652 intracranial aneurysms treated with coil embolization, an IAR occurred in 22 (3.4%). Rupture occurred during placement of coils in 18 cases, microcatheters in 2 cases, and a guidewire in 1 case, and during induction of anesthesia in 1 case. Before treatment, 15 of 22 (68%) patients were in good clinical condition (WFNS grade I). There were fewer patients with worsening of the WFNS grade following an IAR when the balloon-assisted technique was used (7.7%) compared with when it was not (55.5%) (P = .023). Death occurred in 2 (9.1%) patients. CONCLUSIONS: IAR is a potentially serious complication of coil embolization. If IAR occurs, balloon-assistance is helpful in obtaining rapid hemostasis resulting in better short-term outcomes.

Metabolic response of glioblastoma to superselective intra-arterial cerebral infusion of bevacizumab: a proton MR spectroscopic imaging study.

BACKGROUND AND PURPOSE: SIACI of bevacizumab has emerged as a promising novel therapy in the treatment of recurrent GB. This study assessed the potential of (1)H-MRS as an adjunctive technique in detecting metabolic changes reflective of antiproliferative effects of targeted infusion of bevacizumab in the treatment of GB. MATERIALS AND METHODS: Eighteen patients enrolled in a phase I/II study of SIACI of bevacizumab for treatment of recurrent GB were included. Concurrent MR imaging and (1)H-MRS scans were performed before and after treatment. Five distinct morphologic ROIs were evaluated for structural and metabolic changes on MR imaging and (1)H-MRS, which included enhancing, nonenhancing T2 hyperintense signal abnormality, and multiple control regions. Pre- and post-SIACI of bevacizumab peak areas for NAA, tCho, tCr, as well as tCho/tCr and tCho/NAA ratios, were derived for all 5 ROIs and compared using the Wilcoxon signed-rank test. RESULTS: A significant median decrease of 25.99% (range -55.76 to 123.94; P = .006) in tCho/NAA was found post-SIACI of bevacizumab relative to pretreatment values in regions of enhancing disease. A trend-level significant median decrease of 6.45% (range -23.71 to 37.67; P = .06) was noted in tCho/NAA posttreatment in regions of nonenhancing T2-hyperintense signal abnormality. CONCLUSIONS: The results of this (1)H-MRS analysis suggest that GB treatment with SIACI of bevacizumab may be associated with a direct antiproliferative effect, as demonstrated by significant reductions of tCho/NAA after the intervention.

Super-selective basilar artery infusion of bevacizumab and cetuximab for multiply recurrent pediatric ependymoma.

Ependymoma is a central nervous system tumor associated with a poor prognosis due to limited efficacy of current medical treatment modalities, often resulting in multiple surgical re-resections with each tumor recurrence. As traditional chemotherapeutic regimens have proved unsuccessful in long-term control of subtotally resected ependymoma, other agents targeting the tumor microenvironement including the angiogenic factors supplying neovascularization have recently been used. Anti-angiogenic agents such as bevacizumab are routinely used in adult patients with recurrent glioma. Selective intra-arterial cerebral infusion (SIACI) of biological agents within tumor-supplying cerebral vasculature has recently been re-examined as a means to avoid the systemic side-effects associated with intravenous use of bevacizumab. This technical paper describes the first reported use of SIACI for delivery of two targeted biologic agents, bevacizumab and cetuximab in a pediatric patient utilizing the basilar artery to selectively administer the drugs to the tumor microenvironment. We believe this method for therapeutic delivery will both broaden treatment options and better refine treatment methodology as the multi-modality treatment approach often required to treat patients with pediatric ependymomas and other intracranial malignancies evolves.

Intra-arterial chemotherapy for malignant gliomas: a critical analysis.

Intra-arterial (IA) chemotherapy for malignant gliomas including glioblastoma multiforme was initiated decades ago, with many preclinical and clinical studies having been performed since then. Although novel endovascular devices and techniques such as microcatheter or balloon assistance have been introduced into clinical practice, the question remains whether IA therapy is safe and superior to other drug delivery modalities such as intravenous (IV) or oral treatment regimens. This review focuses on IA delivery and surveys the available literature to assess the advantages and disadvantages of IA chemotherapy for treatment of malignant gliomas. In addition, we introduce our hypothesis of using IA delivery to selectively target cancer stem cells residing in the perivascular stem cell niche.

Endovascular treatment of spinal arteriovenous lesions: beyond the dural fistula.

During the past few decades, there have been significant advances in the understanding of spinal vascular lesions, mainly because of the evolution of imaging technology and selective spinal angiography techniques. In this article, we discuss the classification, pathophysiology, and clinical manifestations of spinal vascular lesions other than DAVFs and provide a review of the endovascular approach to treat these lesions.