Publications by authors named "Daniel L Cooke"

92 Publications

How to iGuide: flat panel detector, CT-assisted, minimally invasive evacuation of intracranial hematomas.

J Neurointerv Surg 2021 Oct 11. Epub 2021 Oct 11.

Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, Tennessee, USA

Evidence is growing to support minimally invasive surgical evacuation of intraparenchymal hematomas, particularly those with minimal residual hematoma volumes following evacuation. To maximize the potential for neurologic recovery, it is imperative that the trajectory for access to the hematoma minimizes disruption of normal parenchyma. Flat panel detector CT-based navigation and needle guidance software provides a platform that uses flat panel detector CT imaging obtained on the angiography table to aid reliable and safe access to the hematoma. In addition to providing a high degree of accuracy, this method also allows convenient and rapid re-imaging to assess navigation accuracy and the degree of hematoma evacuation prior to procedural completion. We provide a practical review of the iGuide needle guidance software and the methodology for incorporating its use, and the software of other vendors, in a variety of minimally invasive methods for evacuation of intraparenchymal hematomas.
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http://dx.doi.org/10.1136/neurintsurg-2021-017903DOI Listing
October 2021

Factors associated with seizures at initial presentation in pediatric patients with cerebral arteriovenous malformations.

J Neurosurg Pediatr 2021 Sep 24:1-6. Epub 2021 Sep 24.

1Department of Neurological Surgery, University of California San Francisco, San Francisco.

Objective: Children with cerebral arteriovenous malformations (AVMs) can present with seizures, potentially increasing morbidity and impacting clinical management. However, the factors that lead to seizures as a presenting sign are not well defined. While AVM-related seizures have been described in case series, most studies have focused on adults and have included patients who developed seizures after an AVM rupture. To address this, the authors sought to analyze demographic and morphological characteristics of AVMs in a large cohort of children.

Methods: The demographic, clinical, and AVM morphological characteristics of 189 pediatric patients from a single-center database were studied. Univariate and multivariate logistic regression models were used to test the effect of these characteristics on seizures as an initial presenting symptom in patients with unruptured brain AVMs.

Results: Overall, 28 of 189 patients initially presented with seizures (14.8%). By univariate comparison, frontal lobe location (p = 0.02), larger AVM size (p = 0.003), older patient age (p = 0.04), and the Supplemented Spetzler-Martin (Supp-SM) grade (0.0006) were associated with seizure presentation. Multivariate analysis confirmed an independent effect of frontal lobe AVM location and higher Supp-SM grade. All patients presenting with seizures had AVMs in the cortex or subcortical white matter.

Conclusions: While children and adults share some risk factors for seizure presentation, their risk factor profiles do not entirely overlap. Pediatric patients with cortical AVMs in the frontal lobe were more likely to present with seizures. Additionally, the Supp-SM grade was highly associated with seizure presentation. Future clinical research should focus on the effect of therapeutic interventions targeting AVMs on seizure control in these patients.
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http://dx.doi.org/10.3171/2021.6.PEDS21126DOI Listing
September 2021

Radial artery access anatomy: considerations for neuroendovascular procedures.

J Neurointerv Surg 2021 Sep 22. Epub 2021 Sep 22.

Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA.

Although enthusiasm for transradial access for neurointerventional procedures has grown, a unique set of considerations bear emphasis to preserve safety and minimize complications. In the first part of this review series, we will review important anatomical considerations for safe and easy neuroendovascular procedures from a transradial approach. These include normal and variant radial artery anatomy, the anatomic snuffbox, as well as axillary, brachial, and great vessel arterial anatomy that is imperative for the neuroendovascular surgeon to be intimately familiar prior to pursuing transradial access procedures. In the next part of the review series, we will focus on safety and complications specific to a transradial approach.
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http://dx.doi.org/10.1136/neurintsurg-2021-017871DOI Listing
September 2021

Radial artery access for neuroendovascular procedures: safety review and complications.

J Neurointerv Surg 2021 Sep 22. Epub 2021 Sep 22.

Radiology & Biomedical Imaging, University California San Francisco, San Francisco, California, USA.

Although enthusiasm for transradial access for neurointerventional procedures has grown, a unique set of considerations bear emphasis to preserve safety and minimize complications. In the first part of this review series, we reviewed anatomical considerations for safe and easy neuroendovascular procedures from a transradial approach. In this second part of the review series, we aim to (1) summarize evidence for safety of the transradial approach, and (2) explain complications and their management.
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http://dx.doi.org/10.1136/neurintsurg-2021-017325DOI Listing
September 2021

Robotics for neuroendovascular intervention: Background and primer.

Neuroradiol J 2021 Aug 16:19714009211034829. Epub 2021 Aug 16.

Department of Radiology and Biomedical Imaging, University of California San Francisco, USA.

The simultaneous growth of robotic-assisted surgery and telemedicine in recent years has only been accelerated by the recent coronavirus disease 2019 pandemic. Robotic assistance for neurovascular intervention has garnered significant interest due to opportunities for tele-stroke models of care for remote underserved areas. Lessons learned from medical robots in interventional cardiology and neurosurgery have contributed to incremental but vital advances in medical robotics despite important limitations. In this article, we discuss robot types and their clinical justification and ethics, as well as a general overview on available robots in thoracic/abdominal surgery, neurosurgery, and cardiac electrophysiology. We conclude with current clinical research in neuroendovascular intervention and a perspective on future directions.
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http://dx.doi.org/10.1177/19714009211034829DOI Listing
August 2021

Concurrent presentation of brain arteriovenous malformation, peripheral arteriovenous malformation, and cerebellar astrocytoma: Case report.

Interdiscip Neurosurg 2020 Jun 14;20. Epub 2020 Feb 14.

Department of Radiology and Biomedical Imaging, Division of Neurointerventional Radiology, University of California, San Francisco School of Medicine, San Francisco, CA, United States.

Background: We report a rare case of a 19-year-old female progressively affected by a peripheral arteriovenous malformation (pAVM), a midline cerebellar astrocytoma, and a brain arteriovenous malformation (bAVM).

Case Description: She presented with a pulsatile mass on her left cheek, which was classified as a pAVM through angiography. Following treatment with embolization and surgical resection, she returned with enlargement of the mass and imaging incidentally identified a cerebellar astrocytoma. Suboccipital craniotomy, C1 laminectomy, and endoscopic third ventriculostomy were subsequently performed. She was later treated again for growth of her pAVM, and angiography revealed the presence of a left temporal bAVM, which was resected via a pterional craniotomy.

Conclusions: Pathological staining identified activation of mTOR and RAS/MAPK pathway in the patient's pAVM and bAVM tissue samples. Furthermore, genetic sequencing demonstrated an activating MAPK21 (K57N) mutation in the pAVM and a gain of distal chromosome 7q in the pilocytic astrocytoma. No germline mutation was identified to explain all pathologies. This case demonstrates the need for continued development and further integration of multi-disciplinary genetic, radiological, and neurological treatment teams to effectively care for such complex presentations.
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http://dx.doi.org/10.1016/j.inat.2020.100689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302203PMC
June 2020

Safety and efficacy results of the Flow Redirection Endoluminal Device (FRED) stent system in the treatment of intracranial aneurysms: US pivotal trial.

J Neurointerv Surg 2021 Jul 19. Epub 2021 Jul 19.

Department of Radiology and Biomedical Imaging, UCSF, San Francisco, CA, USA.

Objective: To evaluate the safety and effectiveness of the Flow Redirection Endoluminal Device (FRED) flow diverter in support of an application for Food and Drug Administration approval in the USA.

Methods: 145 patients were enrolled in a prospective, single-arm multicenter trial. Patients with aneurysms of unfavorable morphology for traditional endovascular therapies (large, wide-necked, fusiform, etc) were included. The trial was designed to demonstrate non-inferiority in both safety and effectiveness, comparing trial results with performance goals (PGs) established from peer-reviewed published literature. The primary safety endpoint was death or major stroke (National Institutes of Health Stroke Scale score ≥4 points) within 30 days of the procedure, or any major ipsilateral stroke or neurological death within the first year. The primary effectiveness endpoint was complete occlusion of the target aneurysm with ≤50% stenosis of the parent artery at 12 months after treatment, and in which an alternative treatment of the target intracranial aneurysm had not been performed.

Results: 145 patients underwent attempted placement of a FRED device, and one or more devices were placed in all 145 patients. 135/145 (93%) had a single device placed. Core laboratory adjudication deemed 106 (73.1%) of the aneurysms large or giant. A safety endpoint was experienced by 9/145 (6.2%) patients, successfully achieving the safety PG of <15%. The effectiveness PG of >46% aneurysm occlusion was also achieved, with the effectiveness endpoint being met in 80/139 (57.6%) CONCLUSION: As compared with historically derived performance benchmarks, the FRED flow diverter is both safe and effective for the treatment of appropriately selected intracranial aneurysms.

Clinical Registration Number: NCT01801007.
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http://dx.doi.org/10.1136/neurintsurg-2021-017469DOI Listing
July 2021

Somatic mosaicism in the MAPK pathway in sporadic brain arteriovenous malformation and association with phenotype.

J Neurosurg 2021 Jul 2:1-8. Epub 2021 Jul 2.

Departments of1Anesthesia and Perioperative Care.

Objective: Sporadic brain arteriovenous malformation (BAVM) is a tangled vascular lesion characterized by direct artery-to-vein connections that can cause life-threatening intracerebral hemorrhage (ICH). Recently, somatic mutations in KRAS have been reported in sporadic BAVM, and mutations in other mitogen-activated protein kinase (MAPK) signaling pathway genes have been identified in other vascular malformations. The objectives of this study were to systematically evaluate somatic mutations in MAPK pathway genes in patients with sporadic BAVM lesions and to evaluate the association of somatic mutations with phenotypes of sporadic BAVM severity.

Methods: The authors performed whole-exome sequencing on paired lesion and blood DNA samples from 14 patients with sporadic BAVM, and 295 genes in the MAPK signaling pathway were evaluated to identify genes with somatic mutations in multiple patients with BAVM. Digital droplet polymerase chain reaction was used to validate KRAS G12V and G12D mutations and to assay an additional 56 BAVM samples.

Results: The authors identified a total of 24 candidate BAVM-associated somatic variants in 11 MAPK pathway genes. The previously identified KRAS G12V and G12D mutations were the only recurrent mutations. Overall, somatic KRAS G12V was present in 14.5% of BAVM lesions and G12D was present in 31.9%. The authors did not detect a significant association between the presence or allelic burden of KRAS mutation and three BAVM phenotypes: lesion size (maximum diameter), age at diagnosis, and age at ICH.

Conclusions: The authors confirmed the high prevalence of somatic KRAS mutations in sporadic BAVM lesions and identified several candidate somatic variants in other MAPK pathway genes. These somatic variants may contribute to understanding of the etiology of sporadic BAVM and the clinical characteristics of patients with this condition.
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http://dx.doi.org/10.3171/2020.11.JNS202031DOI Listing
July 2021

Proof-of-concept single-arm trial of bevacizumab therapy for brain arteriovenous malformation.

BMJ Neurol Open 2021 17;3(1):e000114. Epub 2021 Mar 17.

Radiology and Biomedical Imaging, UCSF, San Francisco, California, USA.

Brain arteriovenous malformations (bAVMs) are relatively rare, although their potential for secondary intracranial haemorrhage (ICH) makes their diagnosis and management essential to the community. Currently, invasive therapies (surgical resection, stereotactic radiosurgery and endovascular embolisation) are the only interventions that offer a reduction in ICH risk. There is no designated medical therapy for bAVM, although there is growing animal and human evidence supporting a role for bevacizumab to reduce the size of AVMs. In this single-arm pilot study, two patients with large bAVMs (deemed unresectable by an interdisciplinary team) received bevacizumab 5 mg/kg every 2 weeks for 12 weeks. Due to limitations of external funding, the intended sample size of 10 participants was not reached. Primary outcome measure was change in bAVM volume from baseline at 26 and 52 weeks. No change in bAVM volume was observed 26 or 52 weeks after bevacizumab treatment. No clinically important adverse events were observed during the 52-week study period. There were no observed instances of ICH. Sera vascular endothelial growth factor levels were reduced at 26 weeks and returned to baseline at 52 weeks. This pilot study is the first to test bevacizumab for patients with bAVMs. Bevacizumab therapy was well tolerated in both subjects. No radiographic changes were observed over the 52-week study period. Subsequent larger clinical trials are in order to assess for dose-dependent efficacy and rarer adverse drug effects. Trial registration number: NCT02314377.
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http://dx.doi.org/10.1136/bmjno-2020-000114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204171PMC
March 2021

Endovascular treatment strategy, technique, and outcomes for dural arteriovenous fistulas of the marginal sinus region.

J Neurointerv Surg 2021 May 26. Epub 2021 May 26.

Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA.

Background: Dural arteriovenous fistulas (AVF) of the foramen magnum region (FMR) are technically challenging lesions to treat. Transvenous (TV), transarterial (TA), and surgical approaches have been described, but the optimum treatment strategy is not defined.

Objective: To report treatment strategies and outcomes for FMR-AVF at a single, high-volume referral center.

Methods: A retrospective review from January 2010 to August 2020 identified patients with FMR-AVF at a single referral center. Angiographic features, treatment (observation, endovascular, surgical), and follow-up of angiographic and clinical results were recorded. The technical aspects of TV embolization are then presented in detail.

Results: 29 FMR-AVF were identified in 28 patients. Of these, 24/29 (82.8%) were treated and 5/29 (17.2%) were observed. Treatment was endovascular in 21/24 (87.5%), combined (endovascular+surgical) in 2/24 (8.3%), and surgical in 1/24 (4.2%). Endovascular treatments were 76.2% TV, 14.3% TA, and 9.5% combined TV/TA. Sufficient follow-up data were available for 20/28 (71.4%) with mean follow-up of 16.8 months. No AVF recurrence was seen for TA/TV, combined endovascular/surgical, or surgical groups, and there was one recurrence (7.1%) in the TV group. Symptomatic improvement was seen in all groups: TV (71.4% complete, 28.6% partial), TA (66.7% complete, 33.3% no follow-up), TV+TA (100% partial), endovascular/surgical (100% complete), and surgical (100% partial). Minor non-neurologic complications included 1/14 (7.1%) in the TV group and 1/3 (33.3%) in the TA/TV group.

Conclusion: Endovascular treatment is safe and effective for most FMR-AVF. TV embolization has a high cure rate with few complications.
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http://dx.doi.org/10.1136/neurintsurg-2021-017476DOI Listing
May 2021

The Geometry of Y-Stent Configurations Used for Wide-Necked Aneurysm Treatment: Analyzing Double-Barrel Stents In Vitro Using Flat-Panel Computed Tomography.

World Neurosurg 2021 07 19;151:e363-e371. Epub 2021 Apr 19.

Department of Neurointerventional Radiology, University of California San Francisco, San Francisco, California, USA.

Background: Stent-assisted coil embolization of wide-necked bifurcation aneurysms often employs a Y configuration stent. A similar stent configuration, termed kissing/double-barrel (KDB), is used often at the aortoiliac bifurcation. Studies of KDB stents in aortoiliac disease show that rates of thromboembolic complications vary with the cross-sectional geometry of the stent pair, a function of the radial crush resistive force of each stent. We assessed cross-sectional geometry of intracranial stent pairs in an in vitro model of the basilar artery using flat-panel computed tomography.

Methods: In a silicone model of a wide-necked basilar tip aneurysm, 6 simulated KDB stent deployment trials were performed using combinations of 5 stents (Enterprise 1, Enterprise 2, Neuroform Atlas, LVIS, LVIS Jr.). Flat-panel computed tomography reconstructions were used to assess cross-sectional stent geometry. Relative conformability, defined by ovalization and D-ratio, radial crush resistive force (predicted vs. actual), and radial mismatch fraction were compared by stent type (braided vs. laser-cut).

Results: Several distinct forms of cross-sectional stent geometry were observed. Braided stents had lower ovalization and D-ratio (P = 0.015) than laser-cut stents. The Neuroform Atlas/LVIS combination yielded the lowest radial mismatch fraction (19.7% vs. mean 44.3% ± 0.7%). Braided stents tended to have a deployed stent radius closer to the expected (nominal) diameter (i.e., higher relative crush resistive force) than laser-cut stents (measured vs. nominal diameter discrepancy +38.6% ± 21.1% vs. -10.7% ±16.1%, P = 0.14).

Conclusions: In constant anatomy, cross-sectional geometry of the KDB stent configuration will vary depending on the design and structure of the stents employed.
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http://dx.doi.org/10.1016/j.wneu.2021.04.042DOI Listing
July 2021

Intrasaccular flow disruption (WEB) of a large wide-necked basilar apex aneurysm using PulseRider-assistance.

Interdiscip Neurosurg 2021 Jun 29;24. Epub 2020 Dec 29.

Department of Radiology & Biomedical Imaging, University of California San Francisco, San Francisco, CA 94143, USA.

Large, wide-necked basilar apex aneurysms are difficult to treat. Microsurgical clipping can result in neurologic morbidity and mortality. Endovascular treatment often leaves remnants that need retreatment and/or stent placement with dual antiplatelet therapy. The Woven EndoBridge (WEB) is an intrasaccular flow disruption device that can be used without dual antiplatelet therapy. However, the WEB cannot typically be used in large or giant aneurysms 10 mm because the largest diameter device is the 11 × 9.6 mm single layer sphere (SLS). We present a case in which we use a PulseRider aneurysm neck reconstruction device in the basilar artery to assist in WEB deployment within a 22 mm basilar apex aneurysm with 14 mm neck, thereby permitting aspirin monotherapy postoperatively.
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http://dx.doi.org/10.1016/j.inat.2020.101072DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018600PMC
June 2021

Computed tomography perfusion abnormalities after carotid endarterectomy help in the diagnosis of reversible cerebral vasoconstriction syndrome.

J Vasc Surg Cases Innov Tech 2021 Mar 27;7(1):171-175. Epub 2020 Oct 27.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, School of Medicine, San Francisco, Calif.

Acute neurologic deficits in the postoperative period after carotid endarterectomy (CEA) can prompt extensive diagnostic evaluation. Reversible cerebral vasoconstriction syndrome (RCVS) is an underrecognized cause of acute neurologic deficit after CEA. We present the case of RCVS in an 84-year-old male patient who had experienced left limb weakness after CEA, prompting multiple code stroke activations. The present case is novel because the obtained computed tomography perfusion imaging studies demonstrated abnormalities that have not been previously described in patients with RCVS. These findings, combined with the cerebral angiography findings, led to the rapid diagnosis and delivery of intra-arterial vasodilator therapy. He experienced subsequent resolution of his symptoms and radiologic abnormalities.
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http://dx.doi.org/10.1016/j.jvscit.2020.10.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973125PMC
March 2021

Combined Use of X-ray Angiography and Intraprocedural MRI Enables Tissue-based Decision Making Regarding Revascularization during Acute Ischemic Stroke Intervention.

Radiology 2021 04 9;299(1):167-176. Epub 2021 Feb 9.

From the Department of Radiology & Biomedical Imaging, Division of Interventional Neuroradiology (K.H.N., B.F.K., D.M., A.C., J.M., M.R.A., C.F.D., V.V.H., R.T.H., T.M., M.W.W., D.L.C., S.W.H.), and Department of Neurology (J.V., C.H.S.), University of California San Francisco, 505 Parnassus Ave, L-351, San Francisco, CA 94143-0628; and Siemens Medical Solutions, Malvern, Pa (K.M., H.B.).

Background For patients with acute ischemic stroke undergoing endovascular mechanical thrombectomy with x-ray angiography, the use of adjuncts to maintain vessel patency, such as stents or antiplatelet medications, can increase risk of periprocedural complications. Criteria for using these adjuncts are not well defined. Purpose To evaluate use of MRI to guide critical decision making by using a combined biplane x-ray neuroangiography 3.0-T MRI suite during acute ischemic stroke intervention. Materials and Methods This retrospective observational study evaluated consecutive patients undergoing endovascular intervention for acute ischemic stroke between July 2019 and May 2020 who underwent either angiography with MRI or angiography alone. Cerebral tissue viability was assessed by using MRI as the reference standard. For statistical analysis, Fisher exact test and Student test were used to compare groups. Results Of 47 patients undergoing acute stroke intervention, 12 patients (median age, 69 years; interquartile range, 60-77 years; nine men) underwent x-ray angiography with MRI whereas the remaining 35 patients (median age, 80 years; interquartile range, 68-86 years; 22 men) underwent angiography alone. MRI results influenced clinical decision making in one of three ways: whether or not to perform initial or additional mechanical thrombectomy, whether or not to place an intracranial stent, and administration of antithrombotic or blood pressure medications. In this initial experience, decision making during endovascular acute stroke intervention in the combined angiography-MRI suite was better informed at MRI, such that therapy was guided in real time by the viability of the at-risk cerebral tissue. Conclusion Integrating intraprocedural 3.0-T MRI into acute ischemic stroke treatment was feasible and guided decisions of whether or not to continue thrombectomy, to place stents, or to administer antithrombotic medication or provide blood pressure medications. © RSNA, 2021 See also the editorial by Lev and Leslie-Mazwi in this issue.
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http://dx.doi.org/10.1148/radiol.2021202750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997614PMC
April 2021

Spetzler-Martin Grade III Arteriovenous Malformations: A Multicenter Propensity-Adjusted Analysis of the Effects of Preoperative Embolization.

Neurosurgery 2021 04;88(5):996-1002

Department of Neurosurgery, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona.

Background: Spetzler-Martin (SM) grade III arteriovenous malformations (AVMs) are at the boundary of safe operability, and preoperative embolization may reduce surgical risks.

Objective: To evaluate the benefits of preoperative AVM embolization by comparing neurological outcomes in patients with grade III AVMs treated with or without preoperative embolization.

Methods: All microsurgically treated grade III AVMs were identified from 2011 to 2018 at 2 medical centers. Neurological outcomes, measured as final modified Rankin Scale scores (mRS) and changes in mRS from preoperative baseline to last follow-up evaluation, were compared in patients with and without preoperative embolization.

Results: Of the 102 patients with grade III AVMs who were treated microsurgically, 57 (56%) underwent preoperative embolization. Significant differences were found between the patients with and without embolization in AVM eloquence (74% vs 93%, P = .02), size ≥ 3 cm (47% vs 73%, P = .01), diffuseness (7% vs 22%, P = .04), and mean final mRS (1.1 vs 2.0, P = .005). Poor outcomes were more frequent in patients without embolization (38%) than with embolization (7%) (final mRS > 2; P < .001). Propensity-adjusted analysis revealed AVM resection without embolization was a risk factor for poor outcome (mRS score > 2; odds ratio, 4.2; 95% CI, 1.1-16; P = .03).

Conclusion: Nonembolization of SM grade III AVMs is associated with an increased risk of poor neurological outcomes after microsurgical resection. Preoperative embolization of intermediate-grade AVMs selected because of large AVM size, surgical inaccessibility of feeding arteries, and high flow should be employed more often than anticipated, even in the context of increasing microsurgical experience with AVMs.
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http://dx.doi.org/10.1093/neuros/nyaa551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8324218PMC
April 2021

The Expanding Cell Diversity of the Brain Vasculature.

Front Physiol 2020 3;11:600767. Epub 2020 Dec 3.

Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA, United States.

The cerebrovasculature is essential to brain health and is tasked with ensuring adequate delivery of oxygen and metabolic precursors to ensure normal neurologic function. This is coordinated through a dynamic, multi-directional cellular interplay between vascular, neuronal, and glial cells. Molecular exchanges across the blood-brain barrier or the close matching of regional blood flow with brain activation are not uniformly assigned to arteries, capillaries, and veins. Evidence has supported functional segmentation of the brain vasculature. This is achieved in part through morphologic or transcriptional heterogeneity of brain vascular cells-including endothelium, pericytes, and vascular smooth muscle. Advances with single cell genomic technologies have shown increasing cell complexity of the brain vasculature identifying previously unknown cell types and further subclassifying transcriptional diversity in cardinal vascular cell types. Cell-type specific molecular transitions or zonations have been identified. In this review, we summarize emerging evidence for the expanding vascular cell diversity in the brain and how this may provide a cellular basis for functional segmentation along the arterial-venous axis.
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http://dx.doi.org/10.3389/fphys.2020.600767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7744630PMC
December 2020

Preface.

Handb Clin Neurol 2021;176:ix

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http://dx.doi.org/10.1016/B978-0-444-64034-5.09987-9DOI Listing
July 2021

Vascular anomalies: Classification and management.

Handb Clin Neurol 2021 ;176:345-360

Departments of Radiology and Biomedical Imaging, Neurological Surgery, Neurology, and Anesthesia and Perioperative Care, University of California San Francisco, School of Medicine, San Francisco, CA, United States. Electronic address:

Vascular anomalies are broadly classified into two major categories: vascular tumors and vascular malformations. Most vascular anomalies are caused by sporadic mosaic gene mutations, and recent genetic studies have advanced our understanding of the molecular pathways involved in their pathogenesis. These findings have suggested new therapeutic approaches to vascular anomalies, focusing on their pathogenetic mechanism. This chapter seeks to integrate an improved molecular understanding within the updated classification system of the International Society for Study of Vascular Anomalies. We emphasize the genetic, radiologic, and interventional aspects of diagnosis and management in hopes of allowing improved multidisciplinary collaboration surrounding these complex and interesting anomalies.
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http://dx.doi.org/10.1016/B978-0-444-64034-5.00003-1DOI Listing
July 2021

Cerebral arteriovenous fistulae.

Handb Clin Neurol 2021 ;176:179-198

Departments of Radiology and Biomedical Imaging, Neurological Surgery, Neurology, and Anesthesia and Perioperative Care, University of California San Francisco, School of Medicine, San Francisco, CA, United States.

Dural arteriovenous fistulae (dAVFs) are diverse, complex lesions that share the common feature of arteriovenous shunting without an intervening nidus. In this chapter, the ensuing discussion is organized by dAVF location, followed by further consideration of less common, distinct types of dAVFs-carotid cavernous fistulae, pial arteriovenous fistulae, and vein of Galen malformations. For each lesion type, epidemiology, clinical presentation, imaging findings, classification considerations, and treatment options are discussed.
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http://dx.doi.org/10.1016/B978-0-444-64034-5.00004-3DOI Listing
July 2021

Brain arteriovenous malformations.

Handb Clin Neurol 2021 ;176:171-178

Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, United States. Electronic address:

Brain arteriovenous malformations are an important cause of intracerebral hemorrhage in the young. Ruptured AVM's are often treated, as the risk of rebleeding is high. The treatment of incidentally discovered, unruptured AVMs is controversial as the morbidity and mortality of treatment may exceed that of the AVM's natural history. Management is multimodal and includes observation with follow up, as well as microsurgical resection, endovascular embolization, and stereotactic radiosurgery. Multidisciplinary teams are important in evaluating patients for treatment. The goal of treatment is complete AVM obliteration while preserving neurologic function.
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http://dx.doi.org/10.1016/B978-0-444-64034-5.00020-1DOI Listing
July 2021

Comparing Occlusive Balloon Performance Using 3-Dimensional Printed Models of Intracranial Aneurysmal Defects.

World Neurosurg 2021 02 13;146:e888-e895. Epub 2020 Nov 13.

Department of Radiology, University of California, San Francisco, California, USA.

Objective: Balloon remodeling microcatheters are essential in assisting endovascular coiling of brain aneurysms, but the performance and pressure requirements of different balloon types when used in aneurysmal defects are currently unknown.

Methods: We used Tinkercad (Autodesk, Montreal, Quebec) to create model vessels with aneurysmal defects and 3-dimensionally printed these designs with polylactic acid using the Ultimaker2 (Ultimaker, Geldermalsen, Netherlands). We constructed a pressurized box capable of reaching physiologic pressures that housed our vessels and then tested compliant remodeling balloons under fluoroscopy from 3 manufacturers: Hyperglide (Medtronic, Minneapolis, Minnesota, USA), Transform (Stryker Neurovascular, Fremont, California, USA), and Scepter C (Microvention, Tustin, California, USA). Each balloon was inflated to a nominal and supranominal point at each defect, and at each inflation the maximum diameter of the balloon and internal balloon pressure were recorded. The Phillips Intellivue (Phillips, Amsterdam, The Netherlands) monitor was adapted for internal balloon pressure monitoring. A multivariate linear regression analysis was performed to model balloon compliance (balloon diameter divided by pressure).

Results: Multivariate regression modeling demonstrated the Scepter balloon had significantly greater compliance compared with both the Hyperglide and Transform balloons (P < 0.001). In addition, we found that Scepter balloons had higher compliance in larger defects compared with the other types of balloons and performance differences based on vessel size.

Conclusions: Scepter balloons require less pressure compared with their counterparts to adequately deform through model defects, specifically in larger aneurysm necks in smaller vessel diameters. This result could inform operators of optimal balloon type and size when trying to minimize balloon pressure in fragile brain aneurysms.
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http://dx.doi.org/10.1016/j.wneu.2020.11.030DOI Listing
February 2021

Virtual 2D angiography from four-dimensional digital subtraction angiography (4D-DSA): A feasibility study.

Interv Neuroradiol 2021 Apr 26;27(2):307-313. Epub 2020 Sep 26.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.

Background: Digital subtraction angiography (DSA) remains the gold standard for angiographic evaluation of cerebrovascular pathology, however, multiple acquisitions requiring additional time and radiation are often needed. In contrast, 3D-DSA provides volumetric information from a single injection but neglects temporal information. Four-dimensional-DSA (4D-DSA) combines temporal information of 2D-DSA with volumetric information of 3D-DSA to provide time-resolved tomographic 3D reconstructions, potentially reducing procedure time and radiation. This work evaluates the diagnostic quality of virtual single-frame 4D-DSA relative to 2D-DSA images by assessing clinicians' ability to evaluate cerebrovascular pathology.

Methods: Single-frame images of four projections from 4D-DSA and their corresponding 2D-DSA images (n = 15) were rated by two neurointerventional radiologists. Images were graded based on diagnostic quality (0 = non-diagnostic, 1 = poor, 2 = acceptable, 3 = good). Dose area product (DAP) for each case was recorded for all 2D-DSA, 4D-DSA acquisitions, and the overall procedure.

Results: The mean diagnostic quality of all four 4D-DSA projections from both raters was 1.75 while the mean of 2D-DSA projections was 2.8. Student's t-test revealed significant difference in diagnostic quality between 4D-DSA and 2D-DSA at all four projections (p < 0.001). On average 4D-DSA acquisitions accounted for 30% dose compared to the overall average aggregated dose per procedure.

Conclusions: The difference in image quality between virtual single-frame 4D-DSA and their respective 2D-DSA images is statistically significant. Furthermore, 4D-DSA acquisitions require less radiation dose than conventional procedures with 2D-DSA acquisitions.
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http://dx.doi.org/10.1177/1591019920961604DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050537PMC
April 2021

Brain Arteriovenous Malformation Recurrence After Apparent Microsurgical Cure: Increased Risk in Children Who Present With Arteriovenous Malformation Rupture.

Stroke 2020 10 11;51(10):2990-2996. Epub 2020 Sep 11.

Division of Neurointerventional Radiology, Department of Radiology and Biomedical Imaging (A.C., G.D., M.T.C., E.R.S., D.L.C., M.R.A., C.F.D., V.V.H., R.T.H., S.W.H.), University of California, San Francisco.

Background And Purpose: Do children have an increased risk for brain arteriovenous malformation (AVM) recurrence compared with adults and does this risk vary depending on initial presentation with AVM rupture?

Methods: We retrospectively studied 115 patients initially presenting with brain AVM under age 25 years who underwent complete surgical resection of the AVM as documented by digital subtraction angiography (DSA) and had delayed follow-up DSA to evaluate for AVM recurrence after apparent initial cure.

Results: The mean time from baseline DSA to follow-up DSA was 2.3 years, ranging from 0 to 15 years. Twelve patients (10.4% of the 115 patient cohort and 16.7% of 72 patients with hemorrhage at initial presentation) demonstrated AVM recurrence on follow-up DSA. All patients with recurrence initially presented with intracranial hemorrhage, and intracranial hemorrhage was a significant predictor of recurrence (log rank =0.037). Among patients with initial hemorrhage, the 5-year recurrence rate was 17.8% (95% CI, 8.3%-35.7%). All recurrences occurred in patients who were children at the time of their initial presentation; the oldest was 15 years of age at the time of initial AVM surgery. The 5-year recurrence rate for children (0-18 years of age) with an initial presentation of hemorrhage was 21.4% (95% CI, 10.1%-41.9%). Using Cox regression, we found the risk of AVM recurrence decreased by 14% per each year increase in age at the time of initial surgical resection (hazard ratio=0.86 [95% CI, 0.75-0.99]; =0.031).

Conclusions: There is a high rate of recurrence of apparently cured brain AVMs in children who initially present with AVM rupture. Imaging follow-up is warranted to prevent re-rupture.
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http://dx.doi.org/10.1161/STROKEAHA.120.030135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731776PMC
October 2020

Controversies and Advances in Adult Intracranial Bypass Surgery in 2020.

Oper Neurosurg (Hagerstown) 2020 12;20(1):1-7

Department of Neurological Surgery, University of California, San Francisco, California.

Cerebral revascularization utilizing a variety of bypass techniques can provide either flow augmentation or flow replacement in the treatment of a range of intracranial pathologies, including moyamoya disease, intracranial atherosclerotic disease, and complex aneurysms that are not amenable to endovascular or simple surgical techniques. Though once routine, the publication of high-quality prospective evidence, along with the development of flow-diverting stents, has limited the indications for extracranial-to-intracranial (EC-IC) bypass. Nevertheless, advances in imaging, assessment of cerebral hemodynamics, and surgical technique have changed the risk-benefit calculus for EC-IC bypass. New variations of revascularization surgery involving multiple anastomoses, flow preserving solutions, IC-IC constructs, and posterior circulation bypasses have been pioneered for otherwise difficult to treat pathology including giant aneurysms, dolichoectasia, and medically refractory intracranial atherosclerosis. This review provides a practical update on recent advances in adult intracranial bypass surgery.
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http://dx.doi.org/10.1093/ons/opaa276DOI Listing
December 2020

An Update on Medications for Brain Arteriovenous Malformations.

Neurosurgery 2020 10;87(5):871-878

Department of Neurological Surgery, University of California, San Francisco, San Francisco, California.

Despite a variety of treatment options for brain arteriovenous malformations (bAVMs), many lesions remain challenging to treat and present significant ongoing risk for hemorrhage. In Vitro investigations have recently led to a greater understanding of the formation, growth, and rupture of bAVMs. This has, in turn, led to the development of therapeutic targets for medications for bAVMs, some of which have begun testing in clinical trials in humans. These include bevacizumab, targeting the vascular endothelial growth factor driven angiogenic pathway; thalidomide or lenalidomide, targeting blood-brain barrier impairment; and doxycycline, targeting matrix metalloproteinase overexpression. A variety of other medications appear promising but either requires adaptation from other disease states or development from early bench studies into the clinical realm. This review aims to provide an overview of the current state of development of medications targeting bAVMs and to highlight their likely applications in the future.
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http://dx.doi.org/10.1093/neuros/nyaa192DOI Listing
October 2020

High-Flow Vascular Malformations in Children.

Semin Neurol 2020 06 6;40(3):303-314. Epub 2020 Apr 6.

Department of Neurological Surgery, University of California San Francisco, San Francisco, California.

Children can have a variety of intracranial vascular anomalies ranging from small and incidental with no clinical consequences to complex lesions that can cause substantial neurologic deficits, heart failure, or profoundly affect development. In contrast to high-flow lesions with direct arterial-to-venous shunts, low-flow lesions such as cavernous malformations are associated with a lower likelihood of substantial hemorrhage, and a more benign course. Management of vascular anomalies in children has to incorporate an understanding of how treatment strategies may affect the normal development of the central nervous system. In this review, we discuss the etiologies, epidemiology, natural history, and genetic risk factors of three high-flow vascular malformations seen in children: brain arteriovenous malformations, intracranial dural arteriovenous fistulas, and vein of Galen malformations.
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http://dx.doi.org/10.1055/s-0040-1708869DOI Listing
June 2020

A New Era of Extended Time Window Acute Stroke Interventions Guided by Imaging.

Neurohospitalist 2020 Jan 19;10(1):29-37. Epub 2019 Aug 19.

Department of Radiology and Biomedical Imaging, University of California San Francisco, CA, USA.

Ischemic stroke is one of the most debilitating and deadliest conditions worldwide. Intravenous t-PA is the current standard treatment within 4 hours after onset of symptoms. Recent randomized controlled trials have demonstrated the efficacy of neurointerventional intra-arterial treatment in acute ischemic stroke. About 20% of acute ischemic stroke are classified as wake-up strokes, which falls out of the conventional treatment time window. New evidence suggests that some patients with longer time from symptom onset (up to 24 hours) may benefit from thrombectomy, probably in part due to variations in collateral circulation among individual patients. Advanced imaging can play a crucial role in identifying patients who could benefit from endovascular intervention presenting within extended treatment time windows. In this article, we review the advanced imaging algorithm for ischemic stroke workup in the multiple studies published to date and summarize the results of the clinical trials for late ischemic stroke that can be clinically useful.
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http://dx.doi.org/10.1177/1941874419870701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6900647PMC
January 2020

Early postmarket results with PulseRider for treatment of wide-necked intracranial aneurysms: a multicenter experience.

J Neurosurg 2019 Nov 8:1-10. Epub 2019 Nov 8.

Departments of1Neurosurgery and.

Objective: Traditionally, stent-assisted coiling and balloon remodeling have been the primary endovascular treatments for wide-necked intracranial aneurysms with complex morphologies. PulseRider is an aneurysm neck reconstruction device that provides parent vessel protection for aneurysm coiling. The objective of this study was to report early postmarket results with the PulseRider device.

Methods: This study was a prospective registry of patients treated with PulseRider at 13 American neurointerventional centers following FDA approval of this device. Data collected included clinical presentation, aneurysm characteristics, treatment details, and perioperative events. Follow-up data included degree of aneurysm occlusion and delayed (> 30 days after the procedure) complications.

Results: A total of 54 aneurysms were treated, with the same number of PulseRider devices, across 13 centers. Fourteen cases were in off-label locations (7 anterior communicating artery, 6 middle cerebral artery, and 1 A1 segment anterior cerebral artery aneurysms). The average dome/neck ratio was 1.2. Technical success was achieved in 52 cases (96.2%). Major complications included the following: 3 procedure-related posterior cerebral artery strokes, a device-related intraoperative aneurysm rupture, and a delayed device thrombosis. Immediately postoperative Raymond-Roy occlusion classification (RROC) class 1 was achieved in 21 cases (40.3%), class 2 in 15 (28.8%), and class 3 in 16 cases (30.7%). Additional devices were used in 3 aneurysms. For those patients with 3- or 6-month angiographic follow-up (28 patients), 18 aneurysms (64.2%) were RROC class 1 and 8 (28.5%) were RROC class 2.

Conclusions: PulseRider is being used in both on- and off-label cases following FDA approval. The clinical and radiographic outcomes are comparable in real-world experience to the outcomes observed in earlier studies. Further experience is needed with the device to determine its role in the neurointerventionalist's armamentarium, especially with regard to its off-label use.
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http://dx.doi.org/10.3171/2019.5.JNS19313DOI Listing
November 2019

The effect of preoperative embolization and flow dynamics on resection of brain arteriovenous malformations.

J Neurosurg 2019 May 17;132(6):1836-1844. Epub 2019 May 17.

3Radiology and Biomedical Imaging, and.

Objective: Preoperative embolization of brain arteriovenous malformations (AVMs) is performed to facilitate resection, although its impact on surgical performance has not been clearly defined. The authors tested for associations between embolization and surgical performance metrics.

Methods: The authors analyzed AVM cases resected by one neurosurgeon from 2006 to 2017. They tested whether cases with and without embolization differed from one another with respect to patient and AVM characteristics using t-tests for continuous variables and Fisher's exact tests for categorical variables. They used simple and multivariable regression models to test whether surgical outcomes (blood loss, resection time, surgical clip usage, and modified Rankin Scale [mRS] score) were associated with embolization. Additional regression analyses integrated the peak arterial afferent contrast normalized for the size of the region of interest (Cmax/ROI) into models as an additional predictor.

Results: The authors included 319 patients, of whom 151 (47%) had preoperative embolization. Embolized AVMs tended to be larger (38% with diameter > 3 cm vs 19%, p = 0.001), less likely to have hemorrhaged (48% vs 63%, p = 0.013), or be diffuse (19% vs 29%, p = 0.045). Embolized AVMs were more likely to have both superficial and deep venous drainage and less likely to have exclusively deep drainage (32% vs 17% and 12% vs 23%, respectively; p = 0.002). In multivariable analysis, embolization was not a significant predictor of blood loss or mRS score changes, but did predict longer operating times (+29 minutes, 95% CI 2-56 minutes; p = 0.034) and increased clip usage (OR 2.61, 95% CI 1.45-4.71; p = 0.001). Cmax/ROI was not a significant predictor, although cases with large Cmax/ROI tended to have longer procedure times (+25 minutes per doubling of Cmax/ROI, 95% CI 0-50 minutes; p = 0.051).

Conclusions: In this series, preoperative embolization was associated with longer median resection times and had no association with intraoperative blood loss or mRS score changes.
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http://dx.doi.org/10.3171/2019.2.JNS182743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858934PMC
May 2019
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