Recently, Neuroform Atlas Stent (NAS) (Stryker Neurovascular, Kalamazoo, MI, USA) with low-profiled, easy handling deliveries is being widely applied for wide-necked intracranial aneurysms [14]. Although stent-assisted coiling (SAC) has been reported to be safe and effective in treating wide-necked aneurysms, this technique requires an adjunctive device (the stent) to be remained within the artery, which can increase the rate of periprocedural thromboembolic events. Generally believed to be caused by microemboli created during or after coil embolization, most thromboembolic events are clinically silent [2]. These lesions can be caused by various intra-procedural embolic sources including friable plaques, dissection of parent vessels, air bubbles, and thrombi within aneurysms and catheters that could only be detected by post-procedural diffusion weighted imaging (DWI) [20]. However, there is increasing evidence that the cumulative burden of ischemic brain injury might cause minor deficits or aggravate vascular dementia, especially in older patients with smaller brain volumes and decreased neuronal plasticity [24].

At a time when the use of NAS is increasing worldwide due to its convenience, the impact of NAS on the occurrence of silent embolic infarction (SEI) after aneurysm coiling remains unclear. Thus, the purpose of this study was to evaluate the incidence and risk factors for SEI after SAC, particularly the impact of NAS on the occurrence of SEI.

The study was approved by the Research Ethics Board of Pusan National University Hospital (IRB number 2305-002-126).

This study investigated the incidence and characteristics of SEI after NAS-assisted coiling for the treatment of UIAs and analyzed several risk factors according to the presence of SEI. The major finding of the study was that SEI lesions were observed in 48 (50%) of total 96 patients and among them, those who had 1-3 lesions accounted for 79.2%. In addition, 69.8% of SEI lesions were <3 mm in diameter. Fortunately, there were no SEI associated with symptom. Older age (≥60 years) was significantly associated with the occurrence of SEI. The volume of SEI lesions was found to be significantly increased in older age (≥60 years), hypertension, and larger aneurysm size (≥5 mm). Furthermore, when comparing the SAC group and the simple coiling group done during the same period, there was no significant difference in the incidence or mean volume of SEI.

NAS can be delivered via a 0.0165- or a 0.017-inch microcatheter such as an Excelsior SL-10 (Stryker Neurovascular), one of the most widely used microcatheters for coil embolization [8,14]. The cell size of the NAS is small compared to that of its old version, which allows better coil retention in aneurysms. However, SAC requires that a foreign body (the stent) remain within the artery, which can increase the risk of procedure-related thromboembolic complications. Most reports on the NAS have concluded that NAS-assisted coil embolization is safe and effective in treating wide-necked aneurysms [10,16,25]. Recently, Kwon and Chung [14] have reported outcomes of SAC using NAS in 123 patients with 130 unruptured wide-necked aneurysms. The authors reported a procedure-related complication rate of 6.2%, including 3.8% of thromboembolism, which had no symptoms. Burkhardt et al. [3] have reported that the incidence of symptomatic thromboembolism in 128 patients with 128 aneurysms treated with NAS-assisted coiling is 4.7%. Despite the explosive increase in global use of this smallest profiled NAS, there has been few reports on SEI after NAS-assisted coiling to the best of our knowledge. Furthermore, according to a recent meta-analysis on the association between SEIs and cognitive function, SEI might be a factor inducing cognitive dysfunction [17]. Therefore, SEI has clinical significance because it can lead to a decline in cognitive function and increase the risk of dementia in the long term [17,24].

Among studies on SEI after aneurysm coiling, there are many studies related to incidence and risk factors. However, few studies have examined characteristics of ischemic lesions. Hahnemann et al. [7] have reported a silent embolism after SAC in their 75 consecutive cases, regardless of the type of stent. Silent embolisms were observed relatively high at 64% in their 75 consecutive patients. 70.1% of silent embolisms had 1-3 ischemic lesions and most (87.1%) of the ischemic lesions were <5 mm in diameter. These characteristics of SEI are very similar to results of our study.

Numerous studies have already investigated postprocedural DWI-positive lesions in endovascular coiling for cerebral aneurysms [1,2,11,12,19]. These lesions can be produced by manipulating the guiding catheter, difficulty of aneurysm selection, event during framing coil, amounts of coils, detachment method, surgeon’s experience, and perioperative antithrombotic agent. In these studies, detection rate is reported very widely at around 10-70%. This variability of incidence can be attributed to reasons such as differences in scan settings of MRI systems, medical conditions of patient, and premedication for periprocedural thromboembolism. The incidence of SEI (50%) in the present study was within the aforementioned range.

Regarding conditions affecting the occurrence of SEI, many studies have shown positive associations between various factors (including older age, dyslipidemia, diabetes mellitus, previous ischemic stroke, presence of white matter lesions, ruptured aneurysms, multiple aneurysms, larger dome size, larger neck size, and longer procedural time) and postprocedural DWI-positive lesions [1,9,13,19,23]. In the present study, older age, hypertension, and larger dome size were positively associated with postprocedural SEI volume, similar to previous reports. Increasing age might be related to tortuous large vessels including aortic arch, brachiocephalic trunk, common and internal carotid arteries, and tortuous origin of the vertebral artery. Catheterizing tortuous arteries could increase the risk of thromboembolism. Seo et al. [22] have reported that the occurrence of SEI increases at an older age of >55 years. The authors assumed that more atherosclerotic changes in the cerebral artery were present in older patients and that these patients were more vulnerable to thromboembolic events. High blood pressure is also well known as an important cause of atherosclerotic change in cerebral blood vessels. It can be easily explained as a risk factor in SEI. Several papers have already demonstrated that larger aneurysms are associated with increased risk of periprocedural ischemic stroke [6,23,26]. Intra-aneurysmal clot is more frequent in larger aneurysms before endovascular treatment and larger aneurysms are more likely to have residual flow within the coil mass than small aneurysms. Furthermore, for stent deployment, large size aneurysms can make it difficult to achieve good wall apposition, thus increasing the risk of periprocedural ischemic stroke. The present study also found that aneurysm size (≥5 mm) was significant risk factor for the occurrence of SEI after NAS-assisted aneurysm coiling. Regarding other risk factors, there are several reports that have proved a close correlation between procedure time and the occurrence of SEI, although not demonstrated in the present study [7,15]. Lee et al. [15] have reported that every 10 minutes increase in the procedure time was independently associated with the risk of thromboembolism, after adjusting the analysis (adjusted odds ratio, 1.11; 95% CI, 1.01-1.21). According to report on SEI after SAC of UIAs studied by Hahnemann et al. [7], the number of patients with DWI lesions was significantly increased in older patients (≥55 years) and longer intervention times (≥120 minutes). In addition, with the recent increase in the application of flow diverter to the treatment of UIAs, flow diverter is also emerging as an important risk factor for the occurrence of SEI [26].

Whether neck remodeling stent increases postprocedural SEI lesions in endovascular treatment for cerebral aneurysm remains controversial. Several studies have demonstrated positive associations between SAC and postprocedural DWI-positive lesions, whereas others have not [5,7,19]. Schubert et al. [21] have compared the rate of embolic events in patients treated with SAC with that in those treated with coiling alone. The authors observed no significant difference in rate of embolic events between the two procedures. In the present study, we observed DWI lesions in 50% of all SAC cases (n=96) and 57.1% of all simple coiling group (n=28). In the group without NAS, the incidence of SEI was rather slightly higher. Although accurate comparisons might be difficult due to the small number of controls, the authors carefully agree that NAS with low profiled has a minimal impact on the occurrence of SEI. This is a surprising result since SAC involves increased technical complexity.

To our best knowledge, there are few studies on the difference in thrombosis incidence according to the type of stent. Nii et al. [18] evaluated the incidence and timed the development of acute in-stent thrombosis during SAC with braided- or laser-cut stents. The authors reported that there was no significant difference in the incidence of in-stent thrombosis between the different stent types and it developed earlier after the placement of braided stents. They suggested lower wall shear stress due to denser metal coverage of braided stents as the reason why thrombus formation occurs earlier in braided than laser-cut stents [4,18].

The present study had several limitations including its retrospective data collection and a small number of control group treated with simple coiling. Thus, effects of possible selection bias cannot be excluded. Another limitation of this study was the lack of acquisition of a pretreatment DWI sequence. Thus, we cannot completely eliminate the possibility that some of the DWI lesions might have been due to other causes including pre-procedural diagnostic angiography. NAS-coil embolization was performed after approximately 2 weeks diagnostic angiography. Therefore, we tried our best to distinguish between previous and new DWI positive lesions through differences in signal intensity. Moreover, owing to a single-center design, the present results might be specific to our techniques and machines. Finally, two different MRI systems were used for assessing the appearance of DWI-positive lesions.

A total of 106 SEI lesions were observed in 48 (50%) of 96 patients. SEI occurred more frequently in older patients and the volume of SEI was found to be significantly increased in older age (≥60 years), hypertension, and aneurysm size ≥5 mm. SEIs are common after NAS-assisted coiling with an incidence comparable to those after simple coiling. Most SEIs were less than 3 mm in diameter and consisted of 1-3 lesions. SEI rarely caused symptoms as expected. They occurred more frequently at an older age. Therefore, the authors agree that the use of NAS in the treatment of UIA does not seem to be associated with an increased risk of thromboembolic events if antiplatelet premedication has been performed well. Further studies should focus on the relationship between SEIs and their long-term clinical effects.