De Novo Cerebral Aneurysm Formation Associated With Proximal Stenosis BACKGROUND: Hemodynamic insults—high wall shear stress (WSS) combined with high positive WSS gradient (WSSG)—have been proposed to link to cerebral aneurysm initiation. We report 4 cases of aneurysms with proximal stenosis, including 1 de novo aneurysm, that might be associated with hemodynamic insults caused by the proximal stenosis. CLINICAL PRESENTATION: In 4 clinical cases, the diameter stenosis was 37% to 49% (mean, 42%) located 2.7 to 4.7 mm (mean, 3.7 mm) from the apex. We performed computational fluid dynamics simulations for 2 cases: a ruptured basilar terminus aneu- rysm with proximal stenosis (which had an angiogram taken 15 years previously that showed no aneurysm and no stenosis) and a cavernous carotid artery aneurysm with proximal stenosis. In both cases, the stenosis caused unphysiologically high WSS (. 7 Pa) at the apex, nearly doubling the WSS and WSSG values. To investigate the relationship between stenosis and distal hemodynamic elevation, we created a series of T-shaped vascular models by varying the degree and location of stenosis. We found that stenosis . 40% by diameter located within 10 mm from the apex caused unphysiologically high WSS and WSSG. All 4 clinical cases satisfied these conditions. CONCLUSION: Proximal stenosis could produce high WSS and high positive WSSG at the apex, thus potentially inducing de novo aneurysm formation. KEY WORDS: Aneurysm formation, Computational fluid dynamics simulations, De novo cerebral aneurysm, Hemodynamic insults, Proximal stenosis, Wall shear stress, Wall shear stress gradient Neurosurgery 73:E1080–E1090, 2013 DOI: 10.1227/NEU.0000000000000065 www.neurosurgery-online.com H emodynamic factors play an important role in the initiation of cerebral aneurysms. Several hemodynamic parameters have been proposed as factors of aneurysm formation. 1-4 Meng et al 4 and Metaxa at al 1 demonstrated in experi- mental models that arterial walls exposed to high wall shear stress (WSS) combined with high positive WSS gradient (WSSG), typically resulting from chronic flow increase at an arterial bifurcation, can undergo destructive remodeling leading to aneu- rysm initiation. 5 The questions naturally arise as to whether similar hemodynamic stress condi- tions might be associated with aneurysm initia- tion in humans and what situation could produce such conditions. To this end, it is noteworthy that several clinical reports have described the formation of de novo aneurysms after an increase in flow after therapeutic carotid artery occlusions. 6,7 How- ever, most de novo aneurysms are not specifically associated with carotid occlusions. 8-13 Thus, the cause and mechanism of aneurysm formation remain unclear. We have recently encountered 4 clinical cases of aneurysms with proximal stenosis. One of them was clearly de novo, for which an angiogram from 15 years previously showed no aneurysm and no stenosis. In this report, we investigated whether the stenosis on the feeding vessel could have caused unphysiologically high WSS and WSSG at the apex to cause the aneurysm formation. Using both patient-specific 3-dimensional (3-D) vascu- lar models and a series of idealized T-shaped bifurcation vascular models with proximal steno- sis, we performed computational fluid dynamics (CFD) simulations to investigate the relationship between proximal stenosis and increased hemo- dynamic insult that is conducive for aneurysm initiation. Kenichi Kono, MD* Osamu Masuo, MD, PhD‡ Naoyuki Nakao, MD, PhD‡ Hui Meng, PhD§ *Department of Neurosurgery, Wakayama Rosai Hospital, Wakayama, Japan; ‡Depart- ment of Neurosurgery, Wakayama Medical University, Wakayama, Japan; §Department of Mechanical & Aerospace Engineering and Toshiba Stroke and Vascular Research Center, University at Buffalo, State Univer- sity of New York, Buffalo, New York Correspondence: Kenichi Kono, MD, Department of Neurosurgery, Wakayama Rosai Hospital, 93-1 Kinomoto, Wakayama 640-8505, Japan. E-mail: vyr01450@gmail.com Received, March 8, 2013. Accepted, June 20, 2013. Published Online, July 8, 2013. Copyright ª 2013 by the Congress of Neurological Surgeons ABBREVIATIONS: BT, basilar terminus; CFD, com- putational fluid dynamics; ICA, internal carotid artery; WSS, wall shear stress; WSS, wall shear stress gradient CASE REPORT TOPIC CASE REPORT E1080 | VOLUME 73 | NUMBER 6 | DECEMBER 2013 www.neurosurgery-online.com Copyright © Congress of Neurological Surgeons. Unauthorized reproduction of this article is prohibited.