ICAS is one of the most common causes of ischemic stroke and has a high risk of recurrence, especially in Asian populations [4,7]. More than 40% of ischemic stroke cases are related to impaired blood circulation of the vertebral and basilar arteries. The risk of disease-related ischemic stroke is higher in symptomatic patients with a high-degree of atherosclerotic stenosis (> 70%) [8]. Patients with ischemic stroke in the posterior circulation usually have more severe symptoms than those with ischemic stroke in the anterior circulation [9]. For ICAS, a number of randomized controlled trials have been conducted to explore the best treatment strategies for preventing the recurrence of ischemic stroke [10–12]. However, the results suggest that intensive drug therapy combined with the control of risk factors has been clearly more efficacious than that of intracranial stenting, which is mainly due to the low recurrence rate of stroke after drug therapy and the relatively high incidence of complications related to endovascular therapy. As such, it may be difficult to perform more efficacious intravascular treatment of ICAS compared to that of drug therapy. However, according to the SAMMPRIS study, patients who received intensive medication had a 5.8% primary-endpoint event rate within 30-day follow-ups, 12.6% one-year endpoint event rate, and a 14.9% three-year endpoint-event rate. In the VISSIT trial, patients who received intensive medication had an even higher 30-day primary-endpoint event rate and one-year endpoint event rate compared to those reported from the SAMMPRIS study. Although the incidence of endpoint events in patients receiving intensive medication is lower than that of patients who receive intracranial stenting, the incidence of endpoint events is still high and unacceptable. The adverse events in these studies occurred after Winspan stenting, suggesting that such adverse events may be related to the open-loop design, large radial force, high head-end hardness, and severe tortuosity of Wingspan stents that make them difficult to pass through blood vessels; in addition, the Wingspan stent is difficult to operate and can easily induce perforating branch events [13]. Therefore, based on our experience in the treatment intracranial aneurysms, we chose Enterprise stents in our present study, which is a more mature stent for ICAS treatment. In addition, after the above two major studies, the CASSISS trial held in China released the first-stage results in 2015 [14]. The CASSISS trial continuously included 100 patients and implanted Winspan stents in 13 large centers, which showed a success rate of stent implantation of 100% and a 2% incidence of stroke and death in the postoperative 30 days, which was significantly lower than the 14.7% and 24.1% in the SAMMPRIS and the VISSIT trials, respectively. These results provide hope for further exploring ICAS endovascular treatments.
The Enterprise stent is a closed-loop self-expanding stent for assisting spring-coil embolization of wide-necked intracranial aneurysms, with a stent diameter of 4.5 mm and which consists of four different lengths—14, 22, 28, and 37 mm—that are suitable for 2.5–4.0-mm intracranial blood vessels. The Enterprise stent has a release of less than 70% and is recyclable. It has a closed-loop design so that it is easily passed through curved blood vessels, and its radial support force is smaller than that of the Winspan stent. The operation and release of the Enterprise stent are simpler than those of the Winspan stent, and its positioning is comparatively more accurate. Moreover, the Winspan stent is more prone to cause intimal hyperplasia and irritation to the vessel wall. Not many Enterprise stenting reports for ICAS treatment are currently available. A study by Vajda et al. [15] used the Enterprise stent for the treatment of symptomatic ICAS, with a success rate of 100%. The main complications occurred in four cases (9.1%) during the perioperative period (30 days), including three cases (6.8%) of ischemic perforating stroke and one case (2.2%) of reperfusion stroke. Among the 42 patients with a median follow-up of 25.6 months (range of 12–57 months), no further TIA or stroke was found. Among the 38 patients who underwent imaging-review follow-ups, three cases (6.81%) experienced > 50% restenosis in the stent after an average follow-up of 22 months. Our present study showed that for patients with symptomatic ICAs, applications of small-sized balloon angioplasty and the Enterprise stent implantation were technically successful with a lower incidence of complications. A study by Feng et al. [16] used the Enterprise stent for symptomatic ICAS treatment, which yielded a successful operation rate of 100% and the stenosis decreased from 79.3 ± 8.1% to 14.9 ± 12.3%. The perioperative ischemic stroke rate was 6.8%, and the hemorrhagic stroke rate was 2.2%. There were no further TIA or strokes during an average follow-up of 25.6 months, and restenosis in the stent was > 50% in 6.8% of the cases. The promising results of these two studies offer hope for improving ICAS treatments. However, these two studies performed ICAS stent implantations in the anterior. Although they had high successful operation rates and the incidences of short-term and long-term postoperative complications were lower than those in the SAMMPRIS trial, they did not perform detailed subgroup analysis, and the number of cases in the basilar artery group was relatively small. In addition, the specific perioperative complications, long-term results, and restenosis of the basilar artery subgroup were unclear. To further evaluate the long-term effect of Enterprise stents in the treatment of severe basilar artery stenosis, our present study performed long-term follow-ups and ultimately yielded more efficacious results. Two cases were found to have complications within the 30-day postoperative follow-ups, and one case (2.7%) had complications from perforating branch events. After active treatment, the symptoms of this patient were relieved for more than a month, and mild residual neurological dysfunction was found. Another case (2.7%) with postoperative complications developed subacute thrombosis in the stent, which was improved after active intra-arterial thrombolysis. Subsequently, no neurological dysfunction remained, with an overall perioperative rate of 5.4% (2/37). No new PCI or TIA occurred in the area receiving blood supply from the offending vessels during follow-ups, and no hyper-perfusion, arterial dissection, or death occurred. For patients who were considered to only have neurological dysfunction as a complication, their overall perioperative complications were 2.7%. The mean follow-up period was 56 ± 21 months (36–66 months). Intra-stent stenosis occurred in two patients (5.4%), and one of them had stable symptoms and continued imaging-review follow-ups. This patient had subacute thrombosis. One patient had TIA and underwent balloon dilation. The remaining patient had no TIA or PCI in the area receiving blood supply from the offending vessels during follow-up and they had 2.7% actual symptomatic stenosis. Collectively, the results of these studies were more promising than those of the restenosis rates of the Wingspan stents (31.2%).
In 2019, the long-awaited WEAVE trial was published [17], which confirmed the perioperative safety of the Wingspan stent. In this trial, the perioperative stroke and mortality rate was 2.6%, which was better than the set target of a 4% event incidence. However, the long-term results of the WEAVE trial require further follow-up. Comparing our results with the WEAVE trial showed that although perioperative complications occurred in two of our cases, basilar artery stenosis accounted for 14% (22 cases) of cases in the WEAVE trial, including two non-fatal strokes, two deaths from stroke, and a total of four patients who had an index event of stroke, hemorrhage, or death. Of the two non-fatal stroke cases, one patient had stroke in the pontine perforating branch of the basilar artery, with the postoperative modified Rankin Scale (mRS) being reduced to a score of 4. Although the incidence of stroke due to perforator occlusion was only 0.7% (1/152) and the total number of perforator events was low, the events affecting the perforating branches of the basilar artery in the WEAVE trial likely reached 4.5% (1/22), which was higher than that of our present findings. Thus, we conclude that Enterprise stenting is more beneficial in the treatment of basilar artery stenosis compared to that of Wingspan stenting. Further follow-ups of the WEAVE trial are needed because this study did not analyze the long-term efficacy of stenting and restenosis.
Our present study focused on preoperative assessment, perioperative management, surgical timing, surgical experience, perforator protection, and problems of restenosis. We used multimodal imaging to evaluate the lesion length, degree of stenosis, cerebral perfusion, and collateral circulation. Additionally, our multimodal imaging was supplemented with HR-MRI to monitor plaque location, shape, signal, thickness, and presence of localized or circular plagues. We also measured the nearby parenchymal signal as a reference to determine the plague texture, and the plague signals were categorized into equal signal, slightly lower/low signals, slightly higher/high signals, and mixed signals. HR-MRI has also been used to analyze plaque textures and locations to minimize events affecting the perforating branches of the basilar artery, especially for patients with hyperlipidemia and hyperglycemia [18]. In addition, multimodal imaging assessment has also been shown to be beneficial for preventing hyper-perfusion [19]. In the present study, during the perioperative period, we controlled blood pressure at a relatively low level of 120–130 mmHg, and we used the implementation of appropriate sedation to reduce the occurrence of cerebral hemorrhage and hyper-perfusion [20]. The bowstring effect should be avoided when loosening the balloon and stent system intraoperatively to prevent tearing of the perforating vessels and to achieve sub-satisfactory results once the balloon is expanded [21]. Perforator stroke (PS) is one of the most common complications of intracranial angioplasty and/or stent implantation [22]. The basilar artery is the most common site of PS among all perforator-rich areas. In the SAMMPRIS trial, the incidence of PS in the basilar artery was 16%. The high perioperative PS rate and its unique blood supply through perforating branches make the basilar artery a key location for studying such complications. Diabetes was associated with a significantly higher incidence of PS (11.4% vs. 2.3%, P = 0.004). Dyslipidemia was another risk factor for atherosclerosis and is associated with a high incidence of PS (7.6% vs. 1.8%, P = 0.045). The incidence of PS in patients with < 18 days difference between the time of the last symptom to the time of operation was higher than that of the patients with > 18 days difference (8.9% vs. 1.5%, P = 0.009), and 5.1% of patients were found to be associated with the PS related to surgery. Therefore, we adjusted our surgical timing to be three weeks after the last symptom onset [23]. The main cause of restenosis is the development of intimal hyperplasia, which might be related to dilated trauma, stent thrombosis, inflammatory responses of the blood vessel wall to the stent, and high radial force stimulation. The prevention of restenosis in our present study was likely due to reducing the number of balloon expansions, performance of sub-satisfactory expansion, and our choice of the Enterprise stent. Although the Enterprise stent has the capacity of recovery and release, evert effort was made to accurately localize the stent and to complete the release in one attempt. Moreover, the characteristics of the Enterprise stent also reduced the stimulation and cutting of the plague.
In summary, patients who underwent endovascular treatments were evaluated via multimodal imaging in the present study. Intravascular balloon dilation and angioplasty combined with Enterprise stent implantation was found to be a safe and effective technique for treating severe atherosclerotic stenosis of the basilar artery, which yielded a high success rate, low perioperative complication rate, and achieved efficacious medium- and long-term therapeutic outcomes.