INTRODUCTION

Intracranial atherosclerotic stenosis (ICAS) is one of the main causes of stroke, especially in the Asian population (1). The current guidelines for the treatment of ICAS are still antiplatelet aggregation drugs, but for moderate and severe ICAS patients with the drug treatment, the annual recurrence rate of stroke is 10-24% (2). Wingspan stents,self-expandable stents, were approved by FDA for the treatment of ICAS. However, the SAMMPRIS multicenter study was terminated early because the stroke and mortality rate in the wingspan stent group within 30 days were significantly higher than those in the drug treatment group, and the adverse events were twice as high as expected (3). There are few reports on the treatment of intracranial atherosclerotic stenosis with enterprise stents. This study reports the follow-up results of enterprise stent in the treatment of symptomatic complex intracranial atherosclerotic stenosis since 2014.

METHODS

Patient population

53 patients with symptomatic ischemic stroke were treated with enterprise stents in our department from Jan. 2014 to Dec. 2017 (27 patients with symptomatic intracranial stenosis, 21 patients with atherosclerotic intracranial large vessel occlusion and 5 patients with cerebral artery dissection). 20 lesions met the following inclusion criteria: 1) intracranial atherosclerotic stenosis was ≥70% confirmed by DSA using the formulas described by the Warfarin Aspirin Symptomatic Intracranial Disease (WASID) method;2) length of lesion is > 10 mm; 3) cerebral infarction in the blood supply area within 90 days; 4) still with recurrent symptoms under anti-platelet aggregation therapy. Patients with any of the following were excluded: 1) total occlusive lesion; 2)non-atherosclerotic stenosis; 3) preoperative modifined Rankin Scale (mRS) score is over 3; 4)acute cerebral infarction within 24 hours.

Procedures

Preoperative preparation

1) preoperative evaluation of cerebral ischemia degree by cranial CT perfusion or MR perfusion-weighted imaging, and DSA were performed to evaluate path classification [referring to LMA classification (4)], the stenosis rate, the length of lesions, the diameter of proximal and distal vessels,relationship with branch blood vessels and collateral circulation compensation. 2) antiplatelet aggregation drugs (100 mg aspirin plus 75 mg clopidogrel daily)were given before operation for at least 5 days, and thromboela-stogram was used to detect the effect of antiplatelet aggregation drugs. The patients with insufficient platelet inhibition (AA < 50%, ADP <30%) were given an intensive anti-platelet aggregation drug. During the perioperative period,lipid-regulating drugs (Atto vastatin 20 mg qd or Rosuvastatin 10 mg qd) were given for at least 3 months. At the same time, drug therapy for corresponding risk factors was given.

Operation process

Patients were performed under general anesthesia,the femoral artery was punctured with modified seldinger technique, a 6F envoy guiding catheter(Cordis, USA) was introduced through a femoral sheath. The whole body heparinization was achieved by injecting with heparin sodium (1 mg/ kg) through vein. Cerebral angiography was performed prior to the treatments. The stenosis, diameter and length of the target lesion were calculated again. Referring to the diameter of the target lesion, the gateway balloon catheter (Boston Scientific, USA) was selected with 80% of the “normal” parent artery proximal to the stenosis and the length was selected to match the stenosis. With the help of 0.014 in transend or synchro microguide wire (Stryker, USA), the gateway balloon catheter reached stenosis segment,the balloon was dilated slowly, with a final pressure of 6 atm for about 3 minutes. Withdraw the balloon catheter and feed into the select plus microcatheter(stryker, USA) along the microguide wire. Enterprise stent (Cordis, USA) was delivered through microcatheter, located accurately and released after crossing the narrow segment. If the residual stenosis rate was over 50%, the in-stent balloon expansion was carried out. 5 minutes after the release of the stent, the anterior-posterior and lateral arteriography of the responsible artery was performed to confirm the presence of artery and its distal branches. Xper CT was performed to see whether there was hematencephalon. Successful stent placement was defined as complete coverage of the target lesion, no displacement and thrombosis in the stent, and residual stenosis was less than 50%.

Post operation management

After the operation, a dynamic monitoring of electrocardiogram and blood pressure was provided.We kept blood pressure to target value (10%-15%lower than basic blood pressure). A daily dose of aspirin (100 mg) and clopidogrel (75 mg) was recommended for half a year followed by only aspirin(100 mg). The risk factors, such as hypertension,diabetes mellitus and hyperlipoidemia, were given treatment.

Statistics analysis was performed with the SPSS version 21.0 (IBM, Armonk, NY, USA). The baseline,imaging and stenting data of all patients were presented as means ± standard deviation for continuous variables and number for categorical data.Continuous variables were tested with the student t-test and Wilcoxon signed-rank test while categorical data with a Fisher exact test. Factors affecting restenosis were analyzed with the logistic regression method. The significant P value was set at <0.05.

Follow-up and definition of in-stent restenosis

From Jan.2014 to Dec. 2017, 20 patients with 20 lesions received treatment using the enterprise stent,15 (75.0%) were men and 5 (25.0%) were women.Their mean age was 57.20 ± 9.25 years old (age range: 44-70 years old). The details of the 20 lesions included in this study are shown in Tables 1 and 2.Enterprise stent was performed within 90 days for patients with ischemic stroke. The mean stenotic vessel length was 17.46 ± 4.39 mm (length range:11.06-26.98 mm). The mean stenosis rate was 77.45± 8.44% (rate range 70.10-94.52%) and the mean post-stent residual stenosis rate was 24.89 ± 16.61%(rate range: 0.00-48.68%). Images of procedure for a patient was showed in Figure 1.

Statistical methods

方东升的一个在肉体上被去了势的人，但失去了生命的原欲，他反而更能以一颗赤诚的心去面对自然，除了那个不为人知的秘密，他种种行为体现出来的，就是一个高尚而无私的人。因此他内心二十年如一日承受着负罪感的煎熬，直到和岳西在悬崖上命悬一线之际，他主动放弃了自己的生命，摔下悬崖，把生的希望留给了岳西。

RESULTS

Patient characteristics

Patients were followed up by telephone within 30 days, and mRS scale was used to evaluate prognosis(≤2, good prognosis; ＞2, poor prognosis). The first follow-up of DSA was 3-6 months later after the operation, followed by DSA or CTA each year. In the two-dimensional DSA image, ISR was well-defined as >50% stenosis within or immediately adjacent(within 5 mm) to the stent with >20% luminal loss.

The optimal treatment for symptomatic intracranial atheroscleroticstenosis (sICAS) remains controversial. The results of WASID and SAMMPRIS studies show that drug therapy can reduce the stroke recurrence rate. Intracranial stenting can also reducethe stroke recurrence rate by improving the blood flow of responsible lesions (5,6).Wingspan stent is the only self-expandable stent approved by FDA in the United States for the treatment of sICAS. But Lutsep et al. (6) shows that SAMMPRIS results cannot provide evidence to support that wingspan stent angioplasty is superior to intensive drug therapy. Clinical practice shows that the manipulation of winspan is complex, its unique delivery system may not be able to pass through the circuitous lesions and the head of the wingspan stent has lower softness, which can easily cause vascular injury. In addition, the radial support force of wingspan stent is larger and its continuous stimulation to endovascular membrane may lead to in-stent restenosis. It is reported in the literature that the rate of in-stent restenosis by wingspan can be as high as 31.2% (7). Feng et al. (8) considered that it was safer and more effective for long lesions (>15 mm) treated with enterprise stents than wingspan stents. Apollo stent (McroPort, Shanghai) is an intracranial dedicated ball-expanding stent with stent diameter of 2.5-4.0 mm and a stent length of 8-23 mm. In 2015, the VISSIT test results did not support that the treatment of sICAS with ball-expanding stent was better than anti-platelet aggregation drugs (9).Jiang et al. (10) consider the flexibility of apollo stent delivery system was poor. For intracranial vessels with circuitous pathway and longer than 10 mm, its operation failure rate was high, and the light transmittance of stent itself was poor. It was difficult to observe the stent under X-ray after balloon dilatation. Stent shift might occur during withdrawal of guide wire.

Table 1 Basic preoperative clinical data of selected patients

Note: a an Independent Wilcoxon test, b a Fisher exact test, NIHSS the National Institute of Health Stroke Scale, mRS modifined Rankin Scale. Comparing with the value in group in-stent restenosis, the difference is insignificant (P>0.05).

Variables N (%) P value Age, years 57.20 ± 9.25 0.689a Male gender 15 (75.0) 0.601b Hypertension 13 (65.0) 0.270b Hyperlipemia 4 (20.0) 0.491b Diabetes mellitus 6 (30.0) 0.681b Coronary artery disease 1 (5.0) 0.150b Hyperhomocystinemia 2 (10.0) 0.716b Smoking history 3 (15.0) 0.596b NIHSS score before intervention≤3 19 (95.0) 0.850b>3 1 (5.0)NIHSS score at discharge≤3 18 (90.0) 0.716b>3 2 (10.0)mRS score at discharge≤2 20 (100.0) ->3 0 (0.0)mRS score of 3 months after discharge≤2 20 (100.0) ->3 0 (0.0)

Table 2 Characteristics of diseased vessels in selected patients.

Note: ICA internal carotid artery, MCA middle cerebral artery, VA vertebral artery, BA basilar artery, Classification was according to the morphology and access criteria system. Comparing with the value in group in-stent restenosis, the difference is insignificant(P>0.05).

Variables N (%) P value Location (i)Anterior circulation 7 (35.0) 0.730b Posterior circulation 13 (65.0)Location (ii)ICA 3 (15.0) 0.447b MCA 4 (20.0)VA 8 (40.0)BA 5 (25.0)Stenosis grade, %70-79 12 (60.0) -80-89 4 (20.0)90-99 4 (20.0)Vascular lesion length, mm 17.46 ± 4.39 0.546a Reference artery stenosis, mm 77.45 ± 8.44 0.689a Post-stent residual stenosis rate, % 24.89 ± 16.61 0.416a Classification of access (4)I 9 (45.0) -II 10 (50.0)III 1 (5.0)

Figure 1. Images of procedure and follow-up for a patient. The patient presented with vertigo. New infarcts was found in the brainstem on DWI (A); preoperative DSA (B) and successful blood flow was achieved after stenting (C). At 28-month follow-up, angiography showed good patency of the BA (D).

Perioperative complications and follow-up results

“侵权责任”的笼统称谓在很大程度上掩盖了各种责任形态和制度之间的实质差异。在两大法系中，所谓的“侵权责任”都不过是各种基于相异理念的责任形态的混合物，极像一幅“马赛克拼图”。这幅拼图远看是一个整体，但走近观之，却是由形色各异的板块拼凑而成。

DISCUSSION

那我可以怎么做呢？解决方法是什么？她需要的是什么？“正面管教”让我明白：所有的行为背后都有情绪/感觉——我们做什么，怎么做，源于我们的感觉是什么。于是我先辨别她的情绪，发现她要求看电视的时候，都是她没事干的时候（基础家务活儿她现在都能做，我让她自己决定：想做就做，不想做也行）。

At present, enterprise stent therapy for sICAS is reported in few articles, showing that the restenosis rate of enterprise stent is from 3% to 24.7% (8,13-15).Vajda et al. (15) treated 189 patients with ICAD(with 209 lesions) using the enterprise stent, and had a DSA follow-up rate of 83%; they found that the in-stent restenosis rate was 24.7%, lower rate than that of wingspan (31.2%). Duffis et al. (16)considered a high sensitivity and specificity of CTA compared to DSA for the diagnosis of both any intracranial stenosis and for the diagnosis of 50%stenosis, so in our follow-up, 8 lesions (40.0%) were detected by DSA, the rest (60.0%) were checked by CTA, there was 3 (15.0%) in-stent restenosis. Wang et al. (13) considered that the large radial force of the wingspan stent could stimulate intimal hyperplasia and lead to restenosis in the stent, while enterprise was a self-expandable stent with less radial force. It can effectively reduce the rate of in-stent restenosis.At the same time, the continuous and small radial force of enterprise stent was conducive to the gradual recovery of the narrow vascular lumen.

Enterprise stents are self-expandable stents produced by Codman Company in the United States,which were expected to work with coils in the treatment of intracranial wide-necked aneurysms (11).The diameter of the stent is 4.5 mm, and the length ranges from 14 to 37 mm, which provides more choices for operators. The results of Krischek et al.(12) show that enterprise, which has a closed loop design, less radial support, and soft support conduit,is easy to be placed under the guide wire, easy to be released, and to be located more accurately,compared with wingspan.

Miao et al. (17) carried out a prospective study of targeted PTA or PTAS treatment in different types of sICAS patients. They considered that the Mori A lesions of the type I pathway were suitable for apollo stent and Mori B, C type lesions with the type III path were suitable for self-expandable stent. The Mori A lesion with a tortuous path is suitable for simple balloon dilatation with a total technical success rate of 96.3%. In this study, complex lesions were treated with balloon angioplatsy and enterprise stent implantation. The technical success rate was 100%,and only 1 patient (5.0%) had ischemic cerebrovascular complications in perioperative period,which was less than 14.7% of perioperative complications reported by SAMMPRIS.

Success rate of the operation reached 100%. There was only 1 case (5%) with distal arterial embolism which was treated with increasing fluid infusion.20 patients were available for the clinical follow-up 5-38 (13.15 ± 11.33) months after treatment. No patient experienced recurrent TIA or stroke. Overall,8 lesions (40.0%) underwent DSA follow-up examinations and 12 lesions (60.0%) were checked by CT angiography during the follow-up period. 3 lesions (15.0%) developed ISR without any cerebral ischemia symptoms.

Jiang et al. (4) reported that the mortality of Mori A, B and C were 0, 0 and 25%, respectively. And the operation success rate of Access I was significantly higher than III. In this study, there are 9 (45.0%)Access I, 10 (50.0%) Access II and 1 (5.0%) Access III, and the high success rate of operation might be related to the fewer Access III.

In this study, there are 3 cases of in-stent restenosis (including 2 in-stent occlusion and 1 restenosis). The rate of restenosis was 15.0%, which was lower than wingspan’s in-stent restenosis that was registered by American multi-center enterprise in-stent. However, our study had several limitations.The patients enrolled in the study was relatively small,and the follow-up duration was not long. Besides, our study is a single-center experience, a prospective,multicenter, randomized controlled trial is required in the future.

全国家用电器工业信息中心（NAIC）隶属于中国轻工业信息中心，是面向全国家用电器行业服务的专业信息机构，其前身为全国家用电器工业科技情报站。

随着流域经济社会的发展，工程建设突飞猛进，对砂石料的需求量越来越大，长江中下游河道采砂已经成为支撑流域经济发展的重要组成部分。但随之带来的河势稳定、防洪与通航安全、水生态环境保护以及沿江涉水工程和设施的安全等问题也越来越严重，盲目和无序开采将不可避免地带来负面影响，因此长江中下游河道采砂管理极为重要。河道采砂管理是一个涉及河道等自然系统、经济社会发展体系以及生态环境系统的大系统的、动态的复杂课题。

Conclusion

For symptomatic intracranial atherosclerotic stenosis, especially patients with complex lesions,enterprise stent implantation is safe and effective.There is few data in our center due to strict criteria for intracranial stent. Prospective, multicenter,randomized controlled trials against optimal medical treatment are expected.

REFERENCES

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15. Vajda Z, Schmid E, Güthe T, et al. The modified Bose method for the endovascular treatment of intracranial atherosclerotic arterial stenoses using the Enterprise stent.Neurosurgery 2012; 70:91-101.

16. Duffis EJ, Jethwa P, Gupta G, et al. Accuracy of computed tomographic angiography compared to digital subtraction angiography in the diagnosis of intracranial stenosis and its impact on clinical decision-making. J Stroke Cerebrovasc Dis 2013; 22:1013-1017.

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