Endovascular Treatment of Posterior Cerebral Artery Aneurysms With Flow Diversion: Case Series and Systematic Review

Wallace, Adam N.; Grossberg, Jonathan A; Almandoz, Josser E Delgado; Kamran, Mudassar; Roy, Anil K.; Kayan, Yasha; Austin, Matthew J.; Howard, Brian M.; Moran, Christopher J.; Cawley, C. Michael; Cross, DeWitte T.; Dion, Jacques E.; Kansagra, Akash P.; Osbun, Joshua W.

doi:10.1093/neuros/nyx561

Cited by 24 publications

(15 citation statements)

References 36 publications

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“…36 Fusiform aneurysms of the neurovascular tree are difficult to treat and can rupture and cause vessel occlusion or mass effect on nearby perforator vessels, resulting in neurologic deficits. 1,2,32,33 The securing of the aneurysm prior to rupture through maintenance of cerebral blood flow is the goal. Fusiform cerebral aneurysms are difficult to treat with surgery or with endovascular techniques such as stent or coil reconstruction.…”

Section: Supplemental Data Ligand Binding Induces Pdgfrb Dimerizatiomentioning

confidence: 99%

“…Fusiform cerebral aneurysms are difficult to treat with surgery or with endovascular techniques such as stent or coil reconstruction. 32,33 Regardless of treatment option, outcomes for fusiform aneurysm are poor, 32,33 highlighting a need for improved therapies for this select group of vascular lesions. The data presented suggest that some fusiform cerebral aneurysms are caused by activating variants in PDGFRB.…”

Section: Supplemental Data Ligand Binding Induces Pdgfrb Dimerizatiomentioning

confidence: 99%

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Somatic PDGFRB Activating Variants in Fusiform Cerebral Aneurysms

Karasozen

Osbun

Parada

et al. 2019

The American Journal of Human Genetics

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The role of somatic genetic variants in the pathogenesis of intracranial-aneurysm formation is unknown. We identified a 23-year-old man with progressive, right-sided intracranial aneurysms, ipsilateral to an impressive cutaneous phenotype. The index individual underwent a series of genetic evaluations for known connective-tissue disorders, but the evaluations were unrevealing. Paired-sample exome sequencing between blood and fibroblasts derived from the diseased areas detected a single novel variant predicted to cause a p.Tyr562Cys (g.149505130T>C [GRCh37/hg19]; c.1685A>G) change within the platelet-derived growth factor receptor b gene (PDGFRB), a juxtamembrane-coding region. Variant-allele fractions ranged from 18.75% to 53.33% within histologically abnormal tissue, suggesting post-zygotic or somatic mosaicism. In an independent cohort of aneurysm specimens, we detected somatic-activating PDGFRB variants in the juxtamembrane domain or the kinase activation loop in 4/6 fusiform aneurysms (and 0/38 saccular aneurysms; Fisher's exact test, p < 0.001). PDGFRB-variant, but not wild-type, patient cells were found to have overactive auto-phosphorylation with downstream activation of ERK, SRC, and AKT. The expression of discovered variants demonstrated non-ligand-dependent autophosphorylation, responsive to the kinase inhibitor sunitinib. Somatic gain-of-function variants in PDGFRB are a novel mechanism in the pathophysiology of fusiform cerebral aneurysms and suggest a potential role for targeted therapy with kinase inhibitors.

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Section: Supplemental Data Ligand Binding Induces Pdgfrb Dimerizatiomentioning

confidence: 99%

Section: Supplemental Data Ligand Binding Induces Pdgfrb Dimerizatiomentioning

confidence: 99%

Somatic PDGFRB Activating Variants in Fusiform Cerebral Aneurysms

Karasozen

Osbun

Parada

et al. 2019

The American Journal of Human Genetics

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“…The most commonly used FD in the USA, the pipeline Flex embolization device (PED; Medtronic; Minneapolis, Minnesota, USA), was approved by the US Food and Drug Administration in 2011 for the treatment of large and giant unruptured aneurysms of the cavernous and proximal supraclinoid internal carotid artery (ICA). Off label uses of FD for safe and efficacious treatment of aneurysms in other challenging locations have continued to be reported 2–4…”

Section: Introductionmentioning

confidence: 99%

Endovascular management of acute postprocedural flow diverting stent thrombosis

Townsend

Wolfe

Anadani

et al. 2019

J NeuroIntervent Surg

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IntroductionPostprocedural thrombosis is a rare complication after flow diverting stent (FD) implantation for aneurysm treatment with few reported cases in the literature. Management strategies and outcomes associated with this complication have not been reported.MethodsA multicenter retrospective series of cases of acute postprocedural FD thrombosis were compiled and prevalence was calculated based on procedural volumes over a 7 year period. Acute postprocedural FD thrombosis was defined as the development of neurologic deficit with angiographic imaging demonstrating acute thrombus within the index FD stent at least 2 hours following completion of the implantation procedure.ResultsA total of 10 cases of postprocedural thrombosis were identified at five participating centers among a total of 768 patients treated (prevalence 1.3%). Thrombosis occurred a median of 5.5 days after implantation (range 0–83 days). 9/10 patients underwent emergent angiography with intent to perform endovascular reperfusion. A variety of different endovascular treatments were used, including aspiration thrombectomy, retrievable stent thrombectomy, balloon angioplasty, and intra-arterial thrombolytic infusion, without any procedural complications. There were no instances of FD migration, stent kinking, or aneurysm rupture. 90% of patients achieved Thrombolysis in Cerebral Infarction 2B or greater revascularization. Favorable clinical outcomes (modified Rankin Scale score of 0–2) at 3 months were achieved in 88% of patients.ConclusionAcute postprocedural thrombosis of an FD is a rare complication that occurs in approximately 1–2% of patients after aneurysm treatment. Patients presenting with acute postprocedural FD thrombosis should be aggressively managed using large vessel occlusion thrombectomy techniques, as good angiographic and clinical outcomes are possible.

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“…[2][3][4] Stents also diminish flow into the aneurysm sac itself and decrease pressures at high-pressure zones of the aneurysm (distal neck and dome), which further promote stable thrombus formation. [8][9][10] FDs in other unique rupture situations such as blister and dissecting aneurysms have demonstrated value. 1 Flow diverters (FDs) are new generation stents characterized by low porosity and aptly named for their intended mechanism of action, that is, vessel reconstruction with a reduction of flow into the intracranial aneurysm and subsequent redirection along the path of the parent vessel.…”

mentioning

confidence: 99%

“…Although the ICA remains the most frequent indication for FD use, there are several publications citing their off-label use in other locations. [8][9][10] FDs in other unique rupture situations such as blister and dissecting aneurysms have demonstrated value. [11][12][13][14][15] To date, published data on the performance of FDs has been encouraging, with high rates of complete aneurysm occlusion (up to 93% of patients with complete occlusion at 180 days) despite the various sizes and complex geometries of aneurysms treated.…”

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confidence: 99%

Flow diversion for treatment of intracranial aneurysms: Mechanism and implications

Chua

Silveira

Moore

et al. 2019

Annals of Neurology

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Flow diverters are new generation stents that have recently garnered a large amount of interest for use in treatment of intracranial aneurysms. Flow diverters reduce blood flow into the aneurysm, with redirection along the path of the parent vessel. Flow stagnation into the aneurysm and neck coverage with subsequent endothelialization are the important synergistic mechanisms by which the therapy acts. Several studies have examined the mechanisms by which flow diverters subsequently lead to aneurysm occlusion. This review aims to provide a general overview of the flow diverters and their mechanism of action and potential implications. ANN NEUROL 2019;85:793-800 View this article online at wileyonlinelibrary.com.

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Endovascular Treatment of Posterior Cerebral Artery Aneurysms With Flow Diversion: Case Series and Systematic Review

Abstract: The safety and effectiveness profile of flow diverter treatment of PCA aneurysms may be acceptable in select cases.

Cited by 24 publications

References 36 publications

Somatic PDGFRB Activating Variants in Fusiform Cerebral Aneurysms

Somatic PDGFRB Activating Variants in Fusiform Cerebral Aneurysms

Endovascular management of acute postprocedural flow diverting stent thrombosis

Flow diversion for treatment of intracranial aneurysms: Mechanism and implications

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