- Department of Neurosurgery, Showa General Hospital, Kodaira, Tokyo, Japan
- Department of Neurosurgery, The University of Tokyo Hospital, Tokyo, Japan
- Department of Neurosurgery, Fuji Brain Institute and Hospital, Fujinomiya, Shizuoka, Japan
- Department of Pathology, Showa General Hospital, Kodaira, Japan
Department of Neurosurgery, Showa General Hospital, Kodaira, Tokyo, Japan
DOI:10.4103/2152-7806.153709Copyright: © 2015 Fukushima Y. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
How to cite this article: Fukushima Y, Miyawaki S, Inoue T, Shimizu S, Yoshikawa G, Imai H, Saito N, Tsutsumi K. Repeated de novo aneurysm formation after anastomotic surgery: Potential risk of genetic variant RNF213 c.14576G>A. Surg Neurol Int 20-Mar-2015;6:41
How to cite this URL: Fukushima Y, Miyawaki S, Inoue T, Shimizu S, Yoshikawa G, Imai H, Saito N, Tsutsumi K. Repeated de novo aneurysm formation after anastomotic surgery: Potential risk of genetic variant RNF213 c.14576G>A. Surg Neurol Int 20-Mar-2015;6:41. Available from: http://sni.wpengine.com/surgicalint_articles/repeated-de-novo-aneurysm-formation-anastomotic-surgery-potential-risk-genetic-variant-rnf213-c-14576ga/
Background:De novo aneurysm formation after intracranial anastomotic surgery is a relatively rare complication with fewer than 20 reported cases, and the mechanism is still unclear.
Case Description:A 63-year-old male treated for symptomatic internal carotid artery occlusion developed de novo aneurysms twice after anastomoses first of the superficial temporal artery-middle cerebral artery and second of the external carotid artery-radial artery-middle cerebral artery over a 10-year period. The first de novo aneurysm was successfully resected with pathological diagnosis of true aneurysm. The second de novo aneurysm thrombosed naturally after gradual growth. Genetic testing of the patient revealed the c.14576G>A (p.R4859K) variant in ring finger protein 213, which is a susceptibility gene for moyamoya disease.
Conclusions:This genetic variant was probably involved in the repeated de novo aneurysm formation, and this case represents a rare phenotype of the genetic variant.
External carotid artery (ECA)-internal carotid artery (ICA) anastomosis is a well-established surgical procedure for the treatment of ischemic cerebrovascular disease such as moyamoya disease (MMD), and giant cerebral aneurysms combined with major artery ligation.[
We describe an extremely rare case of repeated de novo aneurysm formation after first and second ECA-ICA anastomoses for symptomatic ICA occlusion. Genetic analysis of the patient revealed the c.14576G>A (p.R4859K, rs112735431) variant in ring finger protein 213 (RNF213; a gene located in chromosome 17q; based on the National Center for Biotechnology Information Reference sequence NP_065965.4), which is known to be a susceptibility gene for MMD.[
History and presentation
A 63-year-old male was admitted to Showa General Hospital with right hemiparesis. He had a history of hypertension, and no other risk factor of atherosclerosis. Magnetic resonance (MR) imaging revealed acute cerebral infarction in the left watershed area [
(a) Diffusion-weighted MR image at onset indicating acute watershed infarction due to hemodynamic insufficiency. (b and c) MR angiogram (b) and lateral DSA of the left common carotid artery (c) at the onset showing occlusion of the left ICA at the cervical portion (arrow). (d) Lateral DSA of the left common carotid artery after the first anastomosis in which the blood flow from the STA perfuses both proximal and distal to the anastomotic site (arrow). (e and f) MR angiogram (e) and lateral DSA of the left common carotid artery (f) performed 2.5 years after the first anastomosis showing de novo aneurysm at the anastomotic site (arrow)
First anastomosis and postoperative course
The patient underwent a left superficial temporal artery (STA)-middle cerebral artery (MCA) single anastomosis at the M4 portion with 15 sutures of 10-0 monofilament nylon [
(a) Intraoperative photograph of the first STA-MCA anastomosis (arrowhead). (b and c) Intraoperative photographs of the trapping of the aneurysm and second ECA-RA-M2 and STA-M4 anastomoses showing the de novo aneurysm (arrow) pretrapping view (b), and posttrapping and anastomoses (arrowhead) view (c). d: M4 portion of the MCA distal to the anastomosis; M2: M2 portion of the MCA; p: M4 portion of the MCA proximal to the anastomosis; RA: Radial artery; STA: Superficial temporal artery
The patient underwent trapping of the aneurysm and left ECA-radial artery (RA)-MCA (M2 portion) and STA-MCA (M4 portion) anastomoses. Intraoperative findings showed that the de novo aneurysm at the anastomotic site had adhered to the superficial dura mater and the bottom brain surface with connective tissue. Clipping of the aneurysm was difficult, because the aneurysm was located exactly at the site of anastomosis [
Photomicrographs of resected de novo aneurysm. Left: Wall of the aneurysm dome (arrow) is thinned and consisted of collagen fibers. Asterisk = aneurysm lumen. Elastica van Gieson stain, original magnification ×20. Right: Fragmented smooth muscle cells (arrowhead) are detected throughout the circumference. Alpha-smooth muscle actin stain, original magnification ×20
(a and b) Postoperative lateral DSA of the left common carotid artery (a) and follow-up MR angiogram (b) showing good patency of the ECA-RA-MCA (arrow) and STA-MCA (arrowhead) anastomoses. C–E: T2-weighted MR image (c) and MR angiograms (d and e) performed 6 years after the second anastomosis showing second de novo aneurysm located remote from the anastomotic site (arrow: Aneurysm, arrowhead: Anastomotic site) (f)Lateral DSA of the left common carotid artery exhibiting the dilated artery (M3 portion) without visualization of the aneurysm lumen (arrow)
Follow-up MR angiography showed good patency of the anastomoses and no other abnormal findings over the next 3 years [
Genetic analysis and ethical considerations
The patient's son had been incidentally diagnosed with asymptomatic right MCA occlusion, so these craniocervical major artery diseases were suspected to have some association with genetic factors. The patient was referred to The University of Tokyo Hospital and genetic analysis was performed there as described previously.[
In the present case, the first de novo aneurysm at the anastomotic site was detected at 2.5 years after the STA-MCA anastomosis surgery, and was successfully resected with a pathological diagnosis of true aneurysm. The second de novo aneurysm located remote from the anastomotic site was detected at 4 years after the ECA-RA-MCA anastomosis surgery, and was thrombosed naturally after gradual growth. This unique case represents repeated de novo aneurysm formation after ECA-ICA anastomosis. The extreme rarity of such repeated aneurysm formation and his family history suggested the involvement of genetic predisposing factors, leading us to identify the presence of the genetic variant RNF213 c.14576G>A.
The genetic variant c.14576G>A in RNF213 has significant associations with MMD and various phenotypes of non-MMD intracranial major artery stenosis and occlusion (ICASO).[
Vascular endothelial cells derived from induced pluripotent stem cells obtained from MMD patients carrying the RNF213 variant had reduced angiogenic activities, and overexpression of RNF213 variant in HeLa cells inhibited cell proliferation in vitro.[
We would refer to some limitations of this case report. First, the extreme rarity of the present case cannot be explained only by the presence of the genetic variant. STA-MCA anastomosis is a common surgical procedure for MMD and ICASO, and about 80% of patients with MMD and 20% of patients with ICASO had the genetic variant RNF213 c.14576G>A.[
The present extremely rare case of repeated de novo aneurysm formation after the first STA-MCA and second ECA-RA-MCA anastomoses occurred in a patient with the genetic variant RNF213 c.14576G>A. We consider that the genetic variant was involved in the repeated de novo aneurysm formation, and this case represents a rare phenotype of the genetic variant RNF213 c.14576G>A.
This work was supported by a Grant-in-Aid for Scientific Research (B) (No. 25293304) to Dr. Saito and by grants from SENSHIN Medical Research Foundation to Dr. Miyawaki. The other authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.
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