Publications by authors named "Louis Kim"

156 Publications

Assessing the rate, natural history, and treatment trends of intracranial aneurysms in patients with intracranial dural arteriovenous fistulas: a Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) investigation.

J Neurosurg 2021 Sep 10:1-10. Epub 2021 Sep 10.

Departments of18Neurological Surgery.

Objective: There is a reported elevated risk of cerebral aneurysms in patients with intracranial dural arteriovenous fistulas (dAVFs). However, the natural history, rate of spontaneous regression, and ideal treatment regimen are not well characterized. In this study, the authors aimed to describe the characteristics of patients with dAVFs and intracranial aneurysms and propose a classification system.

Methods: The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database from 12 centers was retrospectively reviewed. Analysis was performed to compare dAVF patients with (dAVF+ cohort) and without (dAVF-only cohort) concomitant aneurysm. Aneurysms were categorized based on location as a dAVF flow-related aneurysm (FRA) or a dAVF non-flow-related aneurysm (NFRA), with further classification as extra- or intradural. Patients with traumatic pseudoaneurysms or aneurysms with associated arteriovenous malformations were excluded from the analysis. Patient demographics, dAVF anatomical information, aneurysm information, and follow-up data were collected.

Results: Of the 1077 patients, 1043 were eligible for inclusion, comprising 978 (93.8%) and 65 (6.2%) in the dAVF-only and dAVF+ cohorts, respectively. There were 96 aneurysms in the dAVF+ cohort; 10 patients (1%) harbored 12 FRAs, and 55 patients (5.3%) harbored 84 NFRAs. Dural AVF+ patients had higher rates of smoking (59.3% vs 35.2%, p < 0.001) and illicit drug use (5.8% vs 1.5%, p = 0.02). Sixteen dAVF+ patients (24.6%) presented with aneurysm rupture, which represented 16.7% of the total aneurysms. One patient (1.5%) had aneurysm rupture during follow-up. Patients with dAVF+ were more likely to have a dAVF located in nonconventional locations, less likely to have arterial supply to the dAVF from external carotid artery branches, and more likely to have supply from pial branches. Rates of cortical venous drainage and Borden type distributions were comparable between cohorts. A minority (12.5%) of aneurysms were FRAs. The majority of the aneurysms underwent treatment via either endovascular (36.5%) or microsurgical (15.6%) technique. A small proportion of aneurysms managed conservatively either with or without dAVF treatment spontaneously regressed (6.2%).

Conclusions: Patients with dAVF have a similar risk of harboring a concomitant intracranial aneurysm unrelated to the dAVF (5.3%) compared with the general population (approximately 2%-5%) and a rare risk (0.9%) of harboring an FRA. Only 50% of FRAs are intradural. Dural AVF+ patients have differences in dAVF angioarchitecture. A subset of dAVF+ patients harbor FRAs that may regress after dAVF treatment.
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http://dx.doi.org/10.3171/2021.1.JNS202861DOI Listing
September 2021

Recurrence after cure in cranial dural arteriovenous fistulas: a collaborative effort by the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR).

J Neurosurg 2021 Sep 10:1-9. Epub 2021 Sep 10.

Departments of18Neurological Surgery.

Objective: Cranial dural arteriovenous fistulas (dAVFs) are often treated with endovascular therapy, but occasionally a multimodality approach including surgery and/or radiosurgery is utilized. Recurrence after an initial angiographic cure has been reported, with estimated rates ranging from 2% to 14.3%, but few risk factors have been identified. The objective of this study was to identify risk factors associated with recurrence of dAVF after putative cure.

Methods: The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) data were retrospectively reviewed. All patients with angiographic cure after treatment and subsequent angiographic follow-up were included. The primary outcome was recurrence, with risk factor analysis. Secondary outcomes included clinical outcomes, morbidity, and mortality associated with recurrence. Risk factor analysis was performed comparing the group of patients who experienced recurrence with those with durable cure (regardless of multiple recurrences). Time-to-event analysis was performed using all collective recurrence events (multiple per patients in some cases).

Results: Of the 1077 patients included in the primary CONDOR data set, 457 met inclusion criteria. A total of 32 patients (7%) experienced 34 events of recurrence at a mean of 368.7 days (median 192 days). The recurrence rate was 4.5% overall. Kaplan-Meier analysis predicted long-term recurrence rates approaching 11% at 3 years. Grade III dAVFs treated with endovascular therapy were statistically significantly more likely to experience recurrence than those treated surgically (13.3% vs 0%, p = 0.0001). Tentorial location, cortical venous drainage, and deep cerebral venous drainage were all risk factors for recurrence. Endovascular intervention and radiosurgery were associated with recurrence. Six recurrences were symptomatic, including 2 with hemorrhage, 3 with nonhemorrhagic neurological deficit, and 1 with progressive flow-related symptoms (decreased vision).

Conclusions: Recurrence of dAVFs after putative cure can occur after endovascular treatment. Risk factors include tentorial location, cortical venous drainage, and deep cerebral drainage. Multimodality therapy can be used to achieve cure after recurrence. A delayed long-term angiographic evaluation (at least 1 year from cure) may be warranted, especially in cases with risk factors for recurrence.
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http://dx.doi.org/10.3171/2021.1.JNS202033DOI Listing
September 2021

Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR): rationale, design, and initial characterization of patient cohort.

J Neurosurg 2021 Sep 10:1-11. Epub 2021 Sep 10.

6Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia.

Objective: Cranial dural arteriovenous fistulas (dAVFs) are rare lesions, hampering efforts to understand them and improve their care. To address this challenge, investigators with an established record of dAVF investigation formed an international, multicenter consortium aimed at better elucidating dAVF pathophysiology, imaging characteristics, natural history, and patient outcomes. This report describes the design of the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) and includes characterization of the 1077-patient cohort.

Methods: Potential collaborators with established interest in the field were identified via systematic review of the literature. To ensure uniformity of data collection, a quality control process was instituted. Data were retrospectively obtained.

Results: CONDOR comprises 14 centers in the United States, the United Kingdom, the Netherlands, and Japan that have pooled their data from 1077 dAVF patients seen between 1990 and 2017. The cohort includes 359 patients (33%) with Borden type I dAVFs, 175 (16%) with Borden type II fistulas, and 529 (49%) with Borden type III fistulas. Overall, 852 patients (79%) presented with fistula-related symptoms: 427 (40%) presented with nonaggressive symptoms such as tinnitus or orbital phenomena, 258 (24%) presented with intracranial hemorrhage, and 167 (16%) presented with nonhemorrhagic neurological deficits. A smaller proportion (224 patients, 21%), whose dAVFs were discovered incidentally, were asymptomatic. Many patients (85%, 911/1077) underwent treatment via endovascular embolization (55%, 587/1077), surgery (10%, 103/1077), radiosurgery (3%, 36/1077), or multimodal therapy (17%, 184/1077). The overall angiographic cure rate was 83% (758/911 treated), and treatment-related permanent neurological morbidity was 2% (27/1467 total procedures). The median time from diagnosis to follow-up was 380 days (IQR 120-1038.5 days).

Conclusions: With more than 1000 patients, the CONDOR registry represents the largest registry of cranial dAVF patient data in the world. These unique, well-annotated data will enable multiple future analyses to be performed to better understand dAVFs and their management.
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http://dx.doi.org/10.3171/2021.1.JNS202790DOI Listing
September 2021

Dural arteriovenous fistulas without cortical venous drainage: presentation, treatment, and outcomes.

J Neurosurg 2021 Sep 10:1-9. Epub 2021 Sep 10.

16Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts.

Objective: Current evidence suggests that intracranial dural arteriovenous fistulas (dAVFs) without cortical venous drainage (CVD) have a benign clinical course. However, no large study has evaluated the safety and efficacy of current treatments and their impact over the natural history of dAVFs without CVD.

Methods: The authors conducted an analysis of the retrospectively collected multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database. Patient demographics and presenting symptoms, angiographic features of the dAVFs, and treatment outcomes of patients with Borden type I dAVFs were reviewed. Clinical and radiological follow-up information was assessed to determine rates of new intracranial hemorrhage (ICH) or nonhemorrhagic neurological deficit (NHND), worsening of venous hyperdynamic symptoms (VHSs), angiographic recurrence, and progression or spontaneous regression of dAVFs over time.

Results: A total of 342 patients/Borden type I dAVFs were identified. The mean patient age was 58.1 ± 15.6 years, and 62% were women. The mean follow-up time was 37.7 ± 54.3 months. Of 230 (67.3%) treated dAVFs, 178 (77%) underwent mainly endovascular embolization, 11 (4.7%) radiosurgery alone, and 4 (1.7%) open surgery as the primary modality. After the first embolization, most dAVFs (47.2%) achieved only partial reduction in early venous filling. Multiple complementary interventions increased complete obliteration rates from 37.9% after first embolization to 46.7% after two or more embolizations, and 55.2% after combined radiosurgery and open surgery. Immediate postprocedural complications occurred in 35 dAVFs (15.2%) and 6 (2.6%) with permanent sequelae. Of 127 completely obliterated dAVFs by any therapeutic modality, 2 (1.6%) showed angiographic recurrence/recanalization at a mean of 34.2 months after treatment. Progression to Borden-Shucart type II or III was documented in 2.2% of patients and subsequent development of a new dAVF in 1.6%. Partial spontaneous regression was found in 22 (21.4%) of 103 nontreated dAVFs. Multivariate Cox regression analysis demonstrated that older age, NHND, or severe venous-hyperdynamic symptoms at presentation and infratentorial location were associated with worse prognosis. Kaplan-Meier curves showed no significant difference for stable/improved symptoms survival probability in treated versus nontreated dAVFs. However, estimated survival times showed better trends for treated dAVFs compared with nontreated dAVFs (288.1 months vs 151.1 months, log-rank p = 0.28). This difference was statistically significant for treated dAVFs with 100% occlusion (394 months, log-rank p < 0.001).

Conclusions: Current therapeutic modalities for management of dAVFs without CVD may provide better symptom control when complete angiographic occlusion is achieved.
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http://dx.doi.org/10.3171/2021.1.JNS202825DOI Listing
September 2021

Outcome Following Hemorrhage From Cranial Dural Arteriovenous Fistulae: Analysis of the Multicenter International CONDOR Registry.

Stroke 2021 Aug 26:STROKEAHA121034707. Epub 2021 Aug 26.

Department of Neurosurgery, University of Illinois at Chicago, Chicago (M.J.K., A.A., S.A.-H.).

Background And Purpose: Dural arteriovenous fistulae can present with hemorrhage, but there remains a paucity of data regarding subsequent outcomes. We sought to use the CONDOR (Consortium for Dural Arteriovenous Fistula Outcomes Research), a multi-institutional registry, to characterize the morbidity and mortality of dural arteriovenous fistula-related hemorrhage.

Methods: A retrospective review of patients in CONDOR who presented with dural arteriovenous fistula-related hemorrhage was performed. Patient characteristics, clinical follow-up, and radiographic details were analyzed for associations with poor outcome (defined as modified Rankin Scale score ≥3).

Results: The CONDOR dataset yielded 262 patients with incident hemorrhage, with median follow-up of 1.4 years. Poor outcome was observed in 17.0% (95% CI, 12.3%-21.7%) at follow-up, including a 3.6% (95% CI, 1.3%-6.0%) mortality. Age and anticoagulant use were associated with poor outcome on multivariable analysis (odds ratio, 1.04, odds ratio, 5.1 respectively). Subtype of hemorrhage and venous shunting pattern of the lesion did not affect outcome significantly.

Conclusions: Within the CONDOR registry, dural arteriovenous fistula-related hemorrhage was associated with a relatively lower morbidity and mortality than published outcomes from other arterialized cerebrovascular lesions but still at clinically consequential rates.
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http://dx.doi.org/10.1161/STROKEAHA.121.034707DOI Listing
August 2021

Endovascular Management of Distal Anterior Cerebral Artery Aneurysms: A Multicenter Retrospective Review.

World Neurosurg 2021 Jul 18. Epub 2021 Jul 18.

Department of Neurosurgery, Division of Neuroendovascular Surgery, Medical University of South Carolina, Charleston, South Carolina, USA.

Introduction: Distal anterior cerebral artery aneurysms (DACAA) are a rare and difficult entity to manage. Endovascular treatment has evolved for safe and durable treatment of these lesions. The objective of this study is to report the safety, efficacy, and outcomes of endovascular treatment of DACAA.

Methods: A retrospective review of DACAA endovascularly treated at 5 different institutions was performed. Data included demographics, rupture status, radiographic features, endovascular technique, complication rates, and long-term angiographic and clinical outcomes. A primary endpoint was a good clinical outcome (modified Rankin scale 0-2). Secondary endpoints included complications and radiographic occlusion at follow-up.

Results: A total of 84 patients were reviewed. The mean age was 56, and 64 (71.4%) were female. Fifty-two (61.9%) aneurysms were ruptured. A good functional outcome was achieved in 59 patients (85.5%). Sixty (71.4%) aneurysms were treated with primary coiling, and the remaining 24 were treated with flow diversion. Adequate occlusion was achieved in 41 (95.3%) aneurysms treated with coiling, and 17 (89.5%) with flow diversion. There were total 11 (13%) complications. In the flow diversion category, there were 2, both related to femoral access. In the coiling category, there were 9: 5 thromboembolic, 3 ruptures, and 1 related to femoral access.

Conclusion: Endovascular treatment, and in particular, flow diversion for DACAA, is safe, feasible, and associated with good long-term angiographic and clinical outcomes.
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http://dx.doi.org/10.1016/j.wneu.2021.07.055DOI Listing
July 2021

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

The effect of Dean, Reynolds, and Womersley number on the flow in a spherical cavity on a curved round pipe. Part 1. Fluid mechanics in the cavity as a canonical flow representing intracranial aneurysms.

J Fluid Mech 2021 May 31;915. Epub 2021 Mar 31.

Department of Mechanical Engineering, University of Washington, Seattle, WA 98105, USA.

Flow in side-wall cerebral aneurysms can be ideally modelled as the combination of flow over a spherical cavity and flow in a curved circular pipe, two canonical flows. Flow in a curved pipe is known to depend on the Dean number , combining the effects of Reynolds number, , and of the curvature along the pipe centreline, . Pulsatility in the flow introduces a dependency on the Womersley number . Using stereo PIV measurements, this study investigated the effect of these three key non-dimensional parameters, by modifying pipe curvature (), flow-rate (), and pulsatility frequency (), on the flow patterns in a spherical cavity. A single counter-rotating vortex was observed in the cavity for all values of pipe curvature and , for both steady and pulsatile inflow conditions. Increasing the pipe curvature impacted both the flow patterns in the pipe and the cavity, by shifting the velocity profile towards the cavity opening and increasing the flow rate into the cavity. The circulation in the cavity was found to collapse well with only the Dean number, for both steady and pulsatile inflows. For pulsatile inflow, the counter-rotating vortex was unstable and the location of its centre over time was impacted by the curvature of the pipe, as well as the and the in the freestream. The circulation in the cavity was higher for steady inflow than for the equivalent average Reynolds and Dean number pulsatile inflow, with very limited impact of the Womersley in the range studied.
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http://dx.doi.org/10.1017/jfm.2020.1114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136084PMC
May 2021

Lagrangian Trajectory Simulation of Platelets and Synchrotron Microtomography Augment Hemodynamic Analysis of Intracranial Aneurysms Treated With Embolic Coils.

J Biomech Eng 2021 Jul;143(7)

Department of Mechanical Engineering, University of Washington, Seattle, WA 98195; Department of Neurological Surgery, University of Washington, Seattle, WA 98195; Stroke and Applied Neuroscience Center, University of Washington, Seattle, WA 98195.

As frequency of endovascular treatments for intracranial aneurysms increases, there is a growing need to understand the mechanisms for coil embolization failure. Computational fluid dynamics (CFD) modeling often simplifies modeling the endovascular coils as a homogeneous porous medium (PM), and focuses on the vascular wall endothelium, not considering the biomechanical environment of platelets. These assumptions limit the accuracy of computations for treatment predictions. We present a rigorous analysis using X-ray microtomographic imaging of the coils and a combination of Lagrangian (platelet) and Eulerian (endothelium) metrics. Four patient-specific, anatomically accurate in vitro flow phantoms of aneurysms are treated with the same patient-specific endovascular coils. Synchrotron tomography scans of the coil mass morphology are obtained. Aneurysmal hemodynamics are computationally simulated before and after coiling, using patient-specific velocity/pressure measurements. For each patient, we analyze the trajectories of thousands of platelets during several cardiac cycles, and calculate residence times (RTs) and shear exposure, relevant to thrombus formation. We quantify the inconsistencies of the PM approach, comparing them with coil-resolved (CR) simulations, showing the under- or overestimation of key hemodynamic metrics used to predict treatment outcomes. We fully characterize aneurysmal hemodynamics with converged statistics of platelet RT and shear stress history (SH), to augment the traditional wall shear stress (WSS) on the vascular endothelium. Incorporating microtomographic scans of coil morphology into hemodynamic analysis of coiled intracranial aneurysms, and augmenting traditional analysis with Lagrangian platelet metrics improves CFD predictions, and raises the potential for understanding and clinical translation of computational hemodynamics for intracranial aneurysm treatment outcomes.
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http://dx.doi.org/10.1115/1.4050375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086186PMC
July 2021

Onyx embolization for dural arteriovenous fistulas: a multi-institutional study.

J Neurointerv Surg 2021 Feb 25. Epub 2021 Feb 25.

Department of Neurosurgery, University of Illinois at Chicago, Chicago, Illinois, USA.

Background: Although the liquid embolic agent, Onyx, is often the preferred embolic treatment for cerebral dural arteriovenous fistulas (DAVFs), there have only been a limited number of single-center studies to evaluate its performance.

Objective: To carry out a multicenter study to determine the predictors of complications, obliteration, and functional outcomes associated with primary Onyx embolization of DAVFs.

Methods: From the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database, we identified patients who were treated for DAVF with Onyx-only embolization as the primary treatment between 2000 and 2013. Obliteration rate after initial embolization was determined based on the final angiographic run. Factors predictive of complete obliteration, complications, and functional independence were evaluated with multivariate logistic regression models.

Results: A total 146 patients with DAVFs were primarily embolized with Onyx. Mean follow-up was 29 months (range 0-129 months). Complete obliteration was achieved in 80 (55%) patients after initial embolization. Major cerebral complications occurred in six patients (4.1%). At last follow-up, 84% patients were functionally independent. Presence of flow symptoms, age over 65, presence of an occipital artery feeder, and preprocedural home anticoagulation use were predictive of non-obliteration. The transverse-sigmoid sinus junction location was associated with fewer complications, whereas the tentorial location was predictive of poor functional outcomes.

Conclusions: In this multicenter study, we report satisfactory performance of Onyx as a primary DAVF embolic agent. The tentorium remains a more challenging location for DAVF embolization, whereas DAVFs located at the transverse-sigmoid sinus junction are associated with fewer complications.
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http://dx.doi.org/10.1136/neurintsurg-2020-017109DOI Listing
February 2021

Observation Versus Intervention for Low-Grade Intracranial Dural Arteriovenous Fistulas.

Neurosurgery 2021 05;88(6):1111-1120

Department of Neurosurgery, Brigham and Women's Hospital, Boston, Massachusetts, USA.

Background: Low-grade intracranial dural arteriovenous fistulas (dAVF) have a benign natural history in the majority of cases. The benefit from treatment of these lesions is controversial.

Objective: To compare the outcomes of observation versus intervention for low-grade dAVFs.

Methods: We retrospectively reviewed dAVF patients from institutions participating in the CONsortium for Dural arteriovenous fistula Outcomes Research (CONDOR). Patients with low-grade (Borden type I) dAVFs were included and categorized into intervention or observation cohorts. The intervention and observation cohorts were matched in a 1:1 ratio using propensity scores. Primary outcome was modified Rankin Scale (mRS) at final follow-up. Secondary outcomes were excellent (mRS 0-1) and good (mRS 0-2) outcomes, symptomatic improvement, mortality, and obliteration at final follow-up.

Results: The intervention and observation cohorts comprised 230 and 125 patients, respectively. We found no differences in primary or secondary outcomes between the 2 unmatched cohorts at last follow-up (mean duration 36 mo), except obliteration rate was higher in the intervention cohort (78.5% vs 24.1%, P < .001). The matched intervention and observation cohorts each comprised 78 patients. We also found no differences in primary or secondary outcomes between the matched cohorts except obliteration was also more likely in the matched intervention cohort (P < .001). Procedural complication rates in the unmatched and matched intervention cohorts were 15.4% and 19.2%, respectively.

Conclusion: Intervention for low-grade intracranial dAVFs achieves superior obliteration rates compared to conservative management, but it fails to improve neurological or functional outcomes. Our findings do not support the routine treatment of low-grade dAVFs.
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http://dx.doi.org/10.1093/neuros/nyab024DOI Listing
May 2021

Transcirculation approach for stent-assisted coiling of intracranial aneurysms: a multicenter study.

J Neurointerv Surg 2021 Aug 17;13(8):711-715. Epub 2020 Nov 17.

Department of Neurosurgery, Geisinger Health System, Danville, PA, USA.

Background: The transcirculation approach (TCA) for stent-assisted coiling (SAC) of intracranial aneurysms may be useful for certain wide-neck bifurcation aneurysms as well as those with acute-angle efferent branches.

Objective: To describe a multicenter experience using the TCA for SAC.

Methods: A multicenter, retrospective study (2016-2020) of aneurysm treatment using SAC via the TCA. Angiographic outcome was scored using the Raymond Scale (adequate occlusion 1 and 2), and clinical outcome was scored using a modified Rankin Scale (good outcome 0-2) RESULTS: Twenty-nine patients with 29 aneurysms were included (62.1% female; average age 61; 89.7% unruptured; 13.8% previously treated; average dome size 6.4 mm; average neck 4.4 mm). Aneurysm locations included internal carotid artery-fetal posterior cerebral artery (n=4), internal carotid artery terminus (n=4), anterior communicating artery (n=8), vertebral artery-posterior inferior cerebellar artery (n=2), and basilar tip (n=11). The TCA used communicating arteries (93.1%; average 1.6 mm), intermediate catheters (51.7%), jailing technique (62.1%), and staged procedures (10.3%). The most common stent was the Neuroform Atlas (Stryker; 69%). Immediate adequate occlusion was obtained in 75.9%, and five patients with inadequate occlusion progressed to adequate occlusion at follow-up. One (3.4%) procedural complication occurred: a watershed stroke in the setting of baseline four-vessel extracranial disease. Two patients had a poor outcome unrelated to the TCA. The majority of patients (86.4%) had a good clinical outcome. One case of in-stent stenosis due to non-compliance with medication was seen, which resolved with medication resumption.

Conclusions: The TCA for SAC can be performed for a variety of aneurysms with a low complication rate and good clinical outcomes.
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http://dx.doi.org/10.1136/neurintsurg-2020-016899DOI Listing
August 2021

Ultrasonographic cystometry for neurogenic bladder using elastography.

Neurourol Urodyn 2021 01 16;40(1):367-375. Epub 2020 Nov 16.

Department of Urology, College of Medicine, Seoul National University, Seoul, South Korea.

Aim: Ultrasound shear wave elastography (SWE) has been used to measure elasticity (Young's modulus: YM) in solid organs. It was reported to show a better correlation with intravesical pressure (Pves) than with compliance, supporting its potential use in noninvasive cystometry. Contrariwise, conceptually, YM should be more correlated with compliance than with Pves. To optimize the potential use of YM as a noninvasive urodynamic study, the relationship between YM, Pves, and compliance was reassessed in this study.

Method: YM was serially measured using SWE along with bladder filling. To overcome problems inherent to current compliance measurements, modified dynamic compliance was developed from cystometry by a locally weighted scatter plot smoothing algorithm. Then it was matched with YM from SWE. YM was also correlated with Pves. Furthermore, to understand the nature of YM, which was measured by ultrasound, the bladder wall's modulus, which was the mathematical assessment of YM derived from cystometric data, was also calculated and compared.

Results: Thirty-two neurogenic bladder patients were included in this study. YM correlated with Pves (r = .72, p < .0001) better than with modified dynamic compliance (r = -0.43, p < .0001). The correlation of YM with Pves was even higher than that with the calculated bladder wall's modulus (r = .52, p < .0001).

Conclusion: YM measured by SWE associates with Pves better than with compliance, confirming the results of previous studies. SWE reflects the integration of both the holding capability of the bladder wall and urine rather than either of one, implying its potential utilization in noninvasive cystometry.
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http://dx.doi.org/10.1002/nau.24570DOI Listing
January 2021

Weekly dengue forecasts in Iquitos, Peru; San Juan, Puerto Rico; and Singapore.

PLoS Negl Trop Dis 2020 10 16;14(10):e0008710. Epub 2020 Oct 16.

Draper, Cambridge, Massachusetts, United States of America.

Background: Predictive models can serve as early warning systems and can be used to forecast future risk of various infectious diseases. Conventionally, regression and time series models are used to forecast dengue incidence, using dengue surveillance (e.g., case counts) and weather data. However, these models may be limited in terms of model assumptions and the number of predictors that can be included. Machine learning (ML) methods are designed to work with a large number of predictors and thus offer an appealing alternative. Here, we compared the performance of ML algorithms with that of regression models in predicting dengue cases and outbreaks from 4 to up to 12 weeks in advance. Many countries lack sufficient health surveillance infrastructure, as such we evaluated the contribution of dengue surveillance and weather data on the predictive power of these models.

Methods: We developed ML, regression, and time series models to forecast weekly dengue case counts and outbreaks in Iquitos, Peru; San Juan, Puerto Rico; and Singapore from 1990-2016. Forecasts were generated using available weekly dengue surveillance, and weather data. We evaluated the agreement between model forecasts and actual dengue observations using Mean Absolute Error and Matthew's Correlation Coefficient (MCC).

Results: For near term predictions of weekly case counts and when using surveillance data, ML models had 21% and 33% less error than regression and time series models respectively. However, using weather data only, ML models did not demonstrate a practical advantage. When forecasting weekly dengue outbreaks 12 weeks in advance, ML models achieved a maximum MCC of 0.61.

Conclusions: Our results identified 2 scenarios when ML models are advantageous over regression model: 1) predicting dengue weekly case counts 4 weeks ahead when dengue surveillance data are available and 2) predicting weekly dengue outbreaks 12 weeks ahead when dengue surveillance data are unavailable. Given the advantages of ML models, dengue early warning systems may be improved by the inclusion of these models.
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http://dx.doi.org/10.1371/journal.pntd.0008710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7567393PMC
October 2020

Economic Impact of COVID-19 on a High-Volume Academic Neurosurgical Practice.

World Neurosurg 2020 11 10;143:e561-e566. Epub 2020 Aug 10.

Department of Neurological Surgery, University of Washington, Seattle, Washington, USA.

Background: Coronavirus disease-2019 (COVID-19) is a novel disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that rapidly spread around the globe. The dramatic increase in the number of cases and deaths have placed tremendous strain on health care systems worldwide. As health care workers and society adjust to focus treatment and prevention of COVID-19, other facets of the health care enterprise are affected, particularly surgical volume and revenue. The purpose of this study was to describe the financial impact of COVID-19 on an academic neurosurgery department.

Methods: A retrospective review of weekly average daily work relative value units (wRVUs) were compared before and after COVID-19 in the fiscal year 2020. A comparative time period of the same months in the year prior was also included for review. We also review strategies for triaging neurosurgical disease as needing emergent, urgent, or routine operative treatment.

Results: Daily average wRVU after COVID-19 dropped significantly with losses in all weeks examined. Of the 7 weeks in the current post-COVID period, the weekly daily average wRVU was 173 (range, 128-363). The mean decline was 51.4% compared with the pre-COVID era. Both inpatient and outpatient revenue was affected.

Conclusions: COVID-19 had a profound detrimental effect on surgical productivity and revenue generation.
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http://dx.doi.org/10.1016/j.wneu.2020.08.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416742PMC
November 2020

Spasm, stenosis and shelves: balloon-assisted tracking techniques in endovascular interventions.

J Cerebrovasc Endovasc Neurosurg 2020 Mar 31;22(1):26-30. Epub 2020 Mar 31.

Department of Radiology, University of Washington School of Medicine, Seattle, WA, USA.

The technique of balloon-assisted tracking (BAT) has been demonstrated in transradial cardio-angiographic procedures. Using three commonly encountered clinical scenarios, we outline the technical details of BAT for managing peripheral and cerebral interventions with challenging vascular access. We describe methods used to overcome vasospasm, stenosis and vascular shelves during interventions for acute ischemic stroke, but these issues are not unique to neuroendovascular cases and the techniques can be applied across all endovascular interventions. We present three acute stroke interventions where anatomic challenges were overcome with the use of endovascular BAT. This article describes a novel application for BAT techniques in endovascular interventions to assist with access in peripheral, cervical and intracranial vessels. These methods can also be used to improve access during diagnostic cerebral angiography. BAT is a useful adjunct when navigating catheters through vasospasm, tortuous anatomy, vascular step-offs or intraluminal plaques.
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http://dx.doi.org/10.7461/jcen.2020.22.1.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307611PMC
March 2020

Minimizing SARS-CoV-2 exposure when performing surgical interventions during the COVID-19 pandemic.

J Neurointerv Surg 2020 Jul 20;12(7):643-647. Epub 2020 May 20.

Neurosurgery, Lenox Hill Hospital, New York, New York, USA.

Background: Infection from the SARS-CoV-2 virus has led to the COVID-19 pandemic. Given the large number of patients affected, healthcare personnel and facility resources are stretched to the limit; however, the need for urgent and emergent neurosurgical care continues. This article describes best practices when performing neurosurgical procedures on patients with COVID-19 based on multi-institutional experiences.

Methods: We assembled neurosurgical practitioners from 13 different health systems from across the USA, including those in hot spots, to describe their practices in managing neurosurgical emergencies within the COVID-19 environment.

Results: Patients presenting with neurosurgical emergencies should be considered as persons under investigation (PUI) and thus maximal personal protective equipment (PPE) should be donned during interaction and transfer. Intubations and extubations should be done with only anesthesia staff donning maximal PPE in a negative pressure environment. Operating room (OR) staff should enter the room once the air has been cleared of particulate matter. Certain OR suites should be designated as covid ORs, thus allowing for all neurosurgical cases on covid/PUI patients to be performed in these rooms, which will require a terminal clean post procedure. Each COVID OR suite should be attached to an anteroom which is a negative pressure room with a HEPA filter, thus allowing for donning and doffing of PPE without risking contamination of clean areas.

Conclusion: Based on a multi-institutional collaborative effort, we describe best practices when providing neurosurgical treatment for patients with COVID-19 in order to optimize clinical care and minimize the exposure of patients and staff.
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http://dx.doi.org/10.1136/neurintsurg-2020-016161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298685PMC
July 2020

Magnetic resonance vessel wall imaging in cerebrovascular diseases

Neurosurg Focus 2019 12 13;47(6):E4. Epub 2019 Dec 13.

Departments of1Neurological Surgery.

Cerebrovascular diseases manifest as abnormalities of and disruption to the intracranial vasculature and its capacity to carry blood to the brain. However, the pathogenesis of many cerebrovascular diseases begins in the vessel wall. Traditional luminal and perfusion imaging techniques do not provide adequate information regarding the differentiation, onset, or progression of disease. Intracranial high-resolution MR vessel wall imaging (VWI) has emerged as an invaluable technique for understanding and evaluating cerebrovascular diseases. The location and pattern of contrast enhancement in intracranial VWI provides new insight into the inflammatory etiology of cerebrovascular diseases and has potential to permit earlier diagnosis and treatment. In this report, technical considerations of VWI are discussed and current applications of VWI in vascular malformations, blunt cerebrovascular injury/dissection, and steno-occlusive cerebrovascular vasculopathies are reviewed.
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http://dx.doi.org/10.3171/2019.9.FOCUS19599DOI Listing
December 2019

Endovascular management of iatrogenic dissection into the petrous segment of the internal carotid artery during mechanical thrombectomy for acute stroke.

J Clin Neurosci 2020 Jan 10;71:273-274. Epub 2019 Dec 10.

University of Washington School of Medicine, Departments of Neurological Surgery, Radiology, Mechanical Engineering, and Stroke and Applied Neuroscience Center, United States. Electronic address:

Iatrogenic dissection of the internal carotid artery is a well-known complication that can occur during mechanical thrombectomy for acute stroke. The vast majority of these injuries are limited to the cervical segment, and only in exceptional circumstances do they require surgical intervention. In the present case, extension of the lesion into the petrous segment of the carotid artery resulted in an acute neurologic decline necessitating emergent endovascular repair. We discuss the nuances of managing an exceptionally rare presentation of this complication.
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http://dx.doi.org/10.1016/j.jocn.2019.11.037DOI Listing
January 2020

Flow Diversion for Treatment of Intracranial Aneurysms in Pediatric Patients: Multicenter Case Series.

Neurosurgery 2020 07;87(1):53-62

Department of Neurosurgery, Baylor College of Medicine, Houston, Texas.

Background: Though the Pipeline Embolization Device (Medtronic) is approved for use in adults 22 yr and older, the high efficacy and long-term durability of the device is attractive for treatment of intracranial aneurysms in younger patients who often have aneurysms less amenable to traditional endovascular treatments.

Objective: To report technical, angiographic, and clinical outcomes in patients aged 21 or below undergoing flow-diversion treatment for intracranial aneurysms.

Methods: Retrospective review across 16 institutions identified 39 patients aged 21 or below undergoing 46 treatment sessions with Pipeline Embolization Device placement between 2012 and 2018. A total of 50 intracranial aneurysms were treated. Details regarding patient demographics, aneurysm characteristics, treatment considerations, clinical outcomes, and aneurysm occlusion were obtained and analyzed in a multicenter database.

Results: A total of 70% of patients were male. Nonsaccular morphology was seen in half of identified aneurysms. Six aneurysms were giant, and five patients were treated acutely after ruptured presentation. Eight patients were younger than 10 yr of age. Complete aneurysm occlusion was seen in 74% of treated aneurysms. Three aneurysms (6%) were retreated. A total of 83% of patients had a modified Rankin Scale scores of ≤2 at last clinical follow-up. There were 2 early mortalities (4.3%) in the immediate postprocedure period because of rerupture of a treated ruptured aneurysm. No recanalization of a previously occluded aneurysm was observed.

Conclusion: Flow-diversion treatment is a safe and effective treatment for intracranial aneurysms in patients younger than 22 yr. Rates of complete aneurysm occlusion and adverse events are comparable for rates seen in older patients.
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http://dx.doi.org/10.1093/neuros/nyz380DOI Listing
July 2020

Platelet Dynamics and Hemodynamics of Cerebral Aneurysms Treated with Flow-Diverting Stents.

Ann Biomed Eng 2020 Jan 23;48(1):490-501. Epub 2019 Sep 23.

Mechanical Engineering, University of Washington, 4000 15th Ave NE, Box 352600, Seattle, WA, 98195, USA.

Flow-diverting stents (FDS) are used to treat cerebral aneurysms. They promote the formation of a stable thrombus within the aneurysmal sac and, if successful, isolate the aneurysmal dome from mechanical stresses to prevent rupture. Platelet activation, a mechanism necessary for thrombus formation, is known to respond to biomechanical stimuli, particularly to the platelets' residence time and shear stress exposure. Currently, there is no reliable method for predicting FDS treatment outcomes, either a priori or after the procedure. Eulerian computational fluid dynamic (CFD) studies of aneurysmal flow have searched for predictors of endovascular treatment outcome; however, the hemodynamics of thrombus formation cannot be fully understood without considering the platelets' trajectories and their mechanics-triggered activation. Lagrangian analysis of the fluid mechanics in the aneurysmal vasculature provides novel metrics by tracking the platelets' residence time (RT) and shear history (SH). Eulerian and Lagrangian parameters are compared for 19 patient-specific cases, both pre- and post-treatment, to assess the degree of change caused by the FDS and subsequent treatment efficacy.
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http://dx.doi.org/10.1007/s10439-019-02368-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837281PMC
January 2020

Transradial intraoperative cerebral angiography: a multicenter case series and technical report.

J Neurointerv Surg 2020 Feb 4;12(2):170-175. Epub 2019 Sep 4.

Department of Neurosurgery, Washington University in St Louis School of Medicine, St Louis, Missouri, USA.

Background: Use of the radial artery as an access site for neurointerventional procedures is gaining popularity after several studies in interventional cardiology have demonstrated superior patient safety, decreased length of stay, and patient preference compared with femoral artery access. The transradial approach has yet to be characterized for intraoperative cerebral angiography.

Objective: To report a multicenter experience on the use of radial artery access in intraoperative cerebral angiography, including case series and discussion of technical nuances.

Methods: 27 patients underwent attempted transradial cerebral angiography betweenMay 2017 and May 2019. Data were collected regarding technique, patient positioning, vessels selected, technical success rate, and access site complications.

Results: 24 of the 27 patients (88.8%) underwent successful transradial intraoperative cerebral angiography. 18 patients (66.7%) were positioned supine, 6 patients (22.2%) were positioned prone, 1 patient (3.7%) was positioned lateral, and 2 patients (7.4%) were positioned three-quarters prone. A total of 31 vessels were selected including 13 right carotid arteries (8 common, 1 external, 4 internal), 11 left carotid arteries (9 common and 2 internal), and 6 vertebral arteries (5 right and 1 left). Two patients (7.4%) required conversion to femoral access in order to complete the intraoperative angiogram (1 due to arterial vasospasm and 1 due to inadvertent venous catheterization). One procedure (3.7%) was aborted because of inability to obtain the appropriate fluoroscopic views due to patient positioning. No patient experienced stroke, arterial dissection, or access site complication.

Conclusions: Transradial intraoperative cerebral angiography is safe and feasible with potential for improved operating room workflow ergonomics, faster patient mobility in the postoperative period, and reduced costs.
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http://dx.doi.org/10.1136/neurintsurg-2019-015207DOI Listing
February 2020

Predictors of preoperative endovascular embolization of meningiomas: subanalysis of anatomic location and arterial supply.

J Neurointerv Surg 2020 Feb 15;12(2):204-208. Epub 2019 Jul 15.

Neurological Surgery, University of Washington, Seattle, Washington, USA.

Introduction: Endovascular embolization of intracranial meningiomas is commonly used as an adjunct to surgical resection. We sought to describe the anatomic locations and vascular supplies of meningiomas to identify characteristics predictive of successful preoperative endovascular embolization.

Methods: We conducted a retrospective review of 139 meningioma cases receiving cerebral angiograms for possible preoperative endovascular embolization at our institution between December 2000 and March 2017. The extent of embolization, arterial supply, anatomic location, and procedural complications were recorded for each case. Univariate and multivariate analyses were performed to identify tumor characteristics that predicted successful embolization.

Results: Of the total meningioma patients undergoing preoperative angiography, 78% (108/139) were successfully embolized, with a 2.8% periprocedural complication rate (3/108). Within the subset of patients with successful embolization, 31% (33/108) achieved complete angiographic embolization. Significant multivariate predictors of embolization (either partial or complete) were convexity/parasagittal locations (OR 5.15, 95% CI 0.93 to 28.54, p=0.060), meningohypophyseal trunk (MHT, OR 4.65, 95% CI 1.63 to 13.23, p=0.004), middle meningeal artery (MMA, OR 10.89, 95% CI 3.43 to 34.64, p<0.001), and ascending pharyngeal artery supply (APA, OR 9.96, 95% CI 1.88 to 52.73, p=0.007). Significant predictors for complete embolization were convexity/parasagittal locations (OR 4.79, 95% CI 1.66 to 13.84, p=0.004) and embolized APA supply (OR 6.94, 95% CI 1.90 to 25.39, p=0.003). Multiple arterial supply was a negative predictor of complete embolization (OR 0.38, 95% CI 0.15 to 0.98, p=0.05).

Conclusions: Tumor characteristics can be used to predict the likelihood of preoperative meningioma embolization. Parasagittal and convexity meningiomas, and those with APA supply, are most likely to achieve complete angiographic embolization.
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http://dx.doi.org/10.1136/neurintsurg-2019-015129DOI Listing
February 2020

A phase II randomized controlled trial of tiopronin for aneurysmal subarachnoid hemorrhage.

J Neurosurg 2019 Jul 12:1-9. Epub 2019 Jul 12.

1Department of Neurological Surgery, Columbia University Medical Center.

Objective: Delayed cerebral ischemia (DCI) is a significant contributor to poor outcomes after aneurysmal subarachnoid hemorrhage (aSAH). The neurotoxin 3-aminopropanal (3-AP) is upregulated in cerebral ischemia. This phase II clinical trial evaluated the efficacy of tiopronin in reducing CSF 3-AP levels in patients with aSAH.

Methods: In this prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial, 60 patients were assigned to receive tiopronin or placebo in a 1:1 ratio. Treatment was commenced within 96 hours after aSAH onset, administered at a dose of 3 g daily, and continued until 14 days after aSAH or hospital discharge, whichever occurred earlier. The primary efficacy outcome was the CSF 3-AP level at 7 ± 1 days after aSAH.

Results: Of the 60 enrolled patients, 29 (97%) and 27 (93%) in the tiopronin and placebo arms, respectively, received more than one dose of the study drug or placebo. At post-aSAH day 7 ± 1, CSF samples were available in 41% (n = 12/29) and 48% (n = 13/27) of patients in the tiopronin and placebo arms, respectively. No difference in CSF 3-AP levels at post-aSAH day 7 ± 1 was observed between the study arms (11 ± 12 nmol/mL vs 13 ± 18 nmol/mL; p = 0.766). Prespecified adverse events led to early treatment cessation for 4 patients in the tiopronin arm and 2 in the placebo arm.

Conclusions: The power of this study was affected by missing data. Therefore, the authors could not establish or refute an effect of tiopronin on CSF 3-AP levels. Additional observational studies investigating the role of 3-AP as a biomarker for DCI may be warranted prior to its use as a molecular target in future clinical trials.Clinical trial registration no.: NCT01095731 (ClinicalTrials.gov).
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http://dx.doi.org/10.3171/2019.4.JNS19478DOI Listing
July 2019

Clinical outcomes and cost-effectiveness analysis for the treatment of basilar tip aneurysms.

J Neurointerv Surg 2019 Dec 25;11(12):1210-1215. Epub 2019 Jun 25.

Department of Neurological Surgery, University of Washington, Seattle, Washington, USA.

Background: Endovascular treatment of basilar tip aneurysms is less invasive than microsurgical clipping, but requires closer follow-up.

Objective: To characterize the additional costs associated with endovascular treatment of basilar tip aneurysms rather than microsurgical clipping.

Materials And Methods: We obtained clinical records and billing information for 141 basilar tip aneurysms treated with clip ligation (n=48) or endovascular embolization (n=93). Costs included direct and indirect costs associated with index hospitalization, as well as re-treatments, follow-up visits, imaging studies, rehabilitation, and disability. Effectiveness of treatment was quantified by converting functional outcomes (modified Rankin Scale (mRS) score) into quality-adjusted life-years (QALYs). Cost-effectiveness was performed using cost/QALY ratios.

Results: Average index hospitalization costs were significantly higher for patients with unruptured aneurysms treated with clip ligation ($71 400 ± $47 100) compared with coil embolization ($33 500 ± $22 600), balloon-assisted coiling ($26 200 ± $11 600), and stent-assisted coiling ($38 500 ± $20 900). Multivariate predictors for higher index hospitalization cost included vasospasm requiring endovascular intervention, placement of a ventriculoperitoneal shunt, longer length of stay, larger aneurysm neck and width, higher Hunt-Hess grade, and treatment-associated complications. At 1 year, endovascular treatment was associated with lower cost/QALY than clip ligation in unruptured aneurysms ($52 000/QALY vs $137 000/QALY, respectively, p=0.006), but comparable rates in ruptured aneurysms ($193 000/QALY vs $233 000/QALY, p=0.277). Multivariate predictors for higher cost/QALY included worse mRS score at discharge, procedural complications, and larger aneurysm width.

Conclusions: Coil embolization of basilar tip aneurysms is associated with a lower cost/QALY. This effect is sustained during follow-up. Clinical condition at discharge is the most significant predictor of overall cost/QALY at 1 year.
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http://dx.doi.org/10.1136/neurintsurg-2019-014747DOI Listing
December 2019

Somatic PDGFRB Activating Variants in Fusiform Cerebral Aneurysms.

Am J Hum Genet 2019 05 25;104(5):968-976. Epub 2019 Apr 25.

Department of Neurosurgery, University of Washington School of Medicine, Seattle, Washington 98195, USA. Electronic address:

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 β 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 auto-phosphorylation, 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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http://dx.doi.org/10.1016/j.ajhg.2019.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506794PMC
May 2019

Genetic correlates of wall shear stress in a patient-specific 3D-printed cerebral aneurysm model.

J Neurointerv Surg 2019 Oct 12;11(10):999-1003. Epub 2019 Apr 12.

Neurological Surgery, University of Washington, Seattle, WA, USA.

Objectives: To study the correlation between wall shear stress and endothelial cell expression in a patient-specific, three-dimensional (3D)-printed model of a cerebral aneurysm.

Materials And Methods: A 3D-printed model of a cerebral aneurysm was created from a patient's angiogram. After populating the model with human endothelial cells, it was exposed to media under flow for 24 hours. Endothelial cell morphology was characterized in five regions of the 3D-printed model using confocal microscopy. Endothelial cells were then harvested from distinct regions of the 3D-printed model for mRNA collection and gene analysis via quantitative polymerase chain reaction (qPCR.) Cell morphology and mRNA measurement were correlated with computational fluid dynamics simulations.

Results: The model was successfully populated with endothelial cells, which survived under flow for 24 hours. Endothelial morphology showed alignment with flow in the proximal and distal parent vessel and aneurysm neck, but disorganization in the aneurysm dome. Genetic analysis of endothelial mRNA expression in the aneurysm dome and distal parent vessel was compared with the proximal parent vessels. ADAMTS-1 and NOS3 were downregulated in the aneurysm dome, while GJA4 was upregulated in the distal parent vessel. Disorganized morphology and decreased ADAMTS-1 and NOS3 expression correlated with areas of substantially lower wall shear stress and wall shear stress gradient in computational fluid dynamics simulations.

Conclusions: Creating 3D-printed models of patient-specific cerebral aneurysms populated with human endothelial cells is feasible. Analysis of these cells after exposure to flow demonstrates differences in both cell morphology and genetic expression, which correlate with areas of differential hemodynamic stress.
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http://dx.doi.org/10.1136/neurintsurg-2018-014669DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6744304PMC
October 2019

Endovascular thrombectomy in pediatric patients with large vessel occlusion.

J Neurointerv Surg 2019 Jul 6;11(7):729-732. Epub 2019 Mar 6.

The Mount Sinai Health System, New York, New York, USA.

Background: Pediatric acute ischemic stroke with underlying large vessel occlusion is a rare disease with significant morbidity and mortality. There is a paucity of data about the safety and outcomes of endovascular thrombectomy in these cases, especially with modern devices.

Methods: We conducted a retrospective review of all pediatric stroke patients who underwent endovascular thrombectomy in nine US tertiary centers between 2008 and 2017.

Results: Nineteen patients (63.2% male) with a mean (SD) age of 10.9(6) years and weight 44.6 (30.8) kg were included. Mean (SD) NIH Stroke Scale (NIHSS) score at presentation was 13.9 (5.7). CT-based assessment was obtained in 88.2% of the patients and 58.8% of the patients had perfusion-based assessment. All procedures were performed via the transfemoral approach. The first-pass device was stentriever in 52.6% of cases and aspiration in 36.8%. Successful revascularization was achieved in 89.5% of the patients after a mean (SD) of 2.2 (1.5) passes, with a mean (SD) groin puncture to recanalization time of 48.7 (37.3) min (median 41.5). The mean (SD) reduction in NIHSS from admission to discharge was 10.2 (6.2). A good neurological outcome was achieved in 89.5% of the patients. One patient had post-revascularization seizure, but no other procedural complications or mortality occurred.

Conclusions: Endovascular thrombectomy is safe and feasible in selected pediatric patients. Technical and neurological outcomes were comparable to adult literature with no safety concerns with the use of standard adult devices in patients as young as 18 months. This large series adds to the growing literature but further studies are warranted.
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http://dx.doi.org/10.1136/neurintsurg-2018-014320DOI Listing
July 2019
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