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Neuroradiology |
1 From the Department of Neurology and Neuroradiology, Beijing Tiantan Hospital, Capital University of Medical Sciences, 6 Tiantan Xili, 100050 Beijing, China. Received January 24, 2006; revision requested March 27; revision received April 9; accepted May 17; final version accepted August 21. Address correspondence to W.J.J. (e-mail: cjr.jiangweijian{at}vip.163.com).
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ABSTRACT |
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 TOP ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONADVANCES IN KNOWLEDGEReferences |
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Materials and Methods: Institutional ethics committee approval was obtained, with waiver of informed consent. Records were reviewed of 181 consecutive elective stent placement procedures in 169 patients (mean age, 51.8 years; 142 male and 27 female patients) with symptomatic intracranial stenosis of more than 50% diameter reduction. Complications were evaluated. Fisher exact or 
2 tests were used to assess statistical differences between rates for discrete variables. Stratification analysis was used to assess the significant relationship (P < .05) between a potential risk factor and a complication.
Results: Complications occurred in 20 patients (11.8%) of 169 patients: Ten patients (5.9%) had stroke (four patients had symptomatic intracranial hemorrhages [ICHs], and two of these patients died; six patients had ischemic strokes). Six patients had target-lesion thrombosis for which intrathrombus thrombolysis resulted in early complete patency without sequelae, two had asymptomatic ICHs, one had transient ischemic attack, and one had asymptomatic dissection. Perioperative noncompliance with antiplatelet therapy was found to be significantly associated with target-lesion thrombosis (two of eight patients [noncompliance] vs four of 161 patients [compliance], P = .027). Stratification analysis revealed a significant correlation between the use of double stents for a lesion and ICH (P = .005).
Conclusion: Cerebrovascular complications from elective stent placement for intracranial stenosis are diverse. The use of double stents for a lesion is an independent risk factor for ICH. Perioperative noncompliance with antiplatelet therapy is associated with a higher frequency of target-lesion thrombosis.
© RSNA, 2007
The annual risk of ipsilateral ischemic stroke in patients with symptomatic intracranial atherosclerotic stenosis may reach 10%–24% despite optimal medical therapy (1–6). Angioplasty with or without stent placement may be a promising treatment option for symptomatic intracranial stenosis (7–18). Stent-assisted angioplasty can diminish the risks of dissection and elastic recoil associated with balloon angioplasty alone, but the procedural risks such as intraluminal thrombus, perforator stroke, and intracranial hemorrhage (ICH) remain a prime concern (7–20). Currently, the reports of cerebrovascular complications in stent placement for intracranial stenosis remain relatively few because of the small number of patients included in such reports or the lack of analysis of factors that might be associated with these complications (13–17,20). Thus, the purpose of our study was to retrospectively evaluate the cerebrovascular complications from elective stent placement for symptomatic intracranial stenosis and to explore preliminarily which factors are associated with complications.
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MATERIALS AND METHODS |
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Two neurologists who specialize in stroke treatment (T.W.L. and K.H.D.) in consensus reviewed the records for 181 consecutive elective stent placement procedures in 169 patients between September 5, 2001, and November 30, 2004. These records included data in 40 patients with symptomatic intracranial stenosis, and these data were published previously (14). There were 142 male and 27 female patients. The mean age was 51.8 years ± 12.76 (standard deviation) (range, 16–79 years; median, 52 years). The qualifying event was stroke in 69 (40.8%) patients and transient ischemic attacks (TIAs) in 100 (59.2%) patients. One hundred forty-three (84.6%) patients had a relevant regional infarct (ie, an infarct in the territory of the stenotic artery on a magnetic resonance image) and 26 (15.4%) did not. These ischemic events and relevant regional infarcts were attributed to 181 intracranial stenoses with a diameter reduction of 50% or more. The reference diameter was that of the normal vessel distal to the stenotic lesion; if the distal vessel was diseased, the diameter of the normal vessel proximal to the stenosis was used as the reference diameter.
Target Lesions
On the basis of the findings of cerebral angiography, 113 of 181 stenoses were located in the anterior circulation and 68 were located in the posterior circulation. Ninety-nine stenoses were at the M1 segment of the middle cerebral artery (MCA), one was at the M2 segment of the MCA, 13 were at the ophthalmic or communicating internal carotid artery, 31 were at the basilar artery, 31 were at the intracranial (fourth part) vertebral artery (VA), five were at the vertebrobasilar junction, and one was at the posterior inferior cerebellar artery. Eighty-two lesions involved bifurcation, and 99 did not. Fifty-nine stenoses were categorized as type A lesions (<5 mm in length, smooth, concentric or mildly eccentric stenosis); 100 stenoses, as type B lesions (5–10 mm in length, eccentric or angled [>45°] stenosis); and 22 stenoses, as type C lesions (>10 mm in length, angled [>90°] stenosis) (14). Forty-eight accesses between the target lesion and the end of the guiding catheter to be placed were categorized as type 1 (mild tortuosity and smooth vessel wall); 84 accesses, as type 2 (moderate tortuosity and irregular vessel wall); and 49 accesses, as type 3 (severe tortuosity) (14).
All except two patients had one or more atherosclerotic risk factors (arterial hypertension, diabetes mellitus, hyperlipidemia, hyperhomocysteinemia, and smoking). In two patients without risk factors, one who was 42 years old had eccentric plaques present in both the main right MCA (90% diameter reduction) and the right communicating internal carotid artery (50% diameter reduction), and these findings supported the idea that atherosclerosis was the likely cause. The other patient who was 16 years old had a spontaneous dissection and stenosis of the left MCA trunk that resulted in stroke and recurrent TIAs despite antithrombotic therapy. The lesion was presumed to be due to fibromuscular dysplasia. Thus, all intracranial stenoses but one were considered atherosclerotic.
Antiplatelet Therapy
The patients were pretreated with 300 mg of aspirin (Bayer, Leverkusen, Germany) daily plus 75 mg of clopidogrel (Sanofi, Paris, France) daily or 250 mg of ticlopidine (Sanofi) twice daily 7 days before surgery. Treatment was continued for at least 6 months after stent placement. Perioperative noncompliance with antiplatelet therapy was defined as no pretreatment with dual antiplatelet therapy or discontinuation of treatment within 30 days after stent placement.
Interventional Procedure
A low-dose nimodipine (Bayer) infusion was started 2 hours before surgery for prevention of vasospasm. Two anticoagulation regimens were employed. In the initial 68 patients, heparin was administered intravenously as a bolus of 3000 U (Shanghai No. 1 Biochemical and Pharmaceutical, Shanghai, China), followed by an infusion at 800 U/h to maintain an activated clotting time between 250 and 300 seconds. In the subsequent 101 patients, the heparin bolus and infusion were reduced to 2000 and 500 U/h, respectively, to maintain an activated clotting time between 160 and 220 seconds, which was the same as that for the protocol of the PROACT (Intra-arterial Pro-urokinase for Acute Ischemic Stroke) II study (21).
Procedures were performed by one of two interventional neuroradiologists (W.J.J. and B.D., who had 20 and 12 years of experience with endovascular therapy, respectively). With local (n = 113) or general (n = 56) anesthesia, a 6-F guiding catheter (Envoy; Cordis, Miami, Fla) was advanced to the distal cervical segment of the internal carotid artery or VA through a 6-F femoral (165 patients) or radial arterial sheath (four patients). A 0.014-inch microwire was carefully steered across the stenosis with road-map guidance and was anchored distally to support the delivery of the stent system. Assembly of a microcatheter and microwire was used in some cases when a single microwire navigation was difficult. Ioversol (Tyco Healthcare, Montreal, Quebec, Canada), 320 mg of iodine per milliliter, was used as a contrast agent during the procedure, and the total volume of ioversol we used ranged from 50 to 150 mL.
Eight types of balloon-expandable stents were used in this study (Table 1). These stents were classified into two categories: the coronary stent and the intracranial stent (Apollo; MicroPort Medical), which was specifically designed for treatment of intracranial stenosis. The coronary stent was used through 2003, after which the intracranial stent was used. The stent length was selected to completely cover the stenosis with an overhang of at least 1 mm on both sides. The diameter of the stent was the same as the diameter of a normal adjacent vessel on either side of the stenosis, whichever adjacent vessel was smaller or slightly smaller than that diameter. The stent was deployed by slow balloon inflation up to 6–8 atm, when the stent straddled the stenotic segment. The second stent was used when the lesion was not covered by the first stent completely. Double stents, which partially overlapped each other, were used in six patients (six lesions).
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Complications
Cerebrovascular complications within 30 days of the procedure were considered perioperative and procedure related (22). ICHs included parenchymal hemorrhage and subarachnoid hemorrhage detected at brain CT. Target-lesion thrombosis was defined as intraluminal thrombus within the vessel treated with a stent or its side branch that was confirmed with cerebral angiography. TIA was defined as acute onset of a focal neurologic deficit that lasted 24 hours or less. Stroke was defined as acute onset of a focal neurologic deficit that lasted longer than 24 hours and that was specifically attributable to a cerebrovascular distribution (23,24). Stroke was further classified into minor stroke (National Institutes of Health Stroke Scale [NIHSS] score of <9) (23) and major stroke (NIHSS score of 
9). Ischemic events consisted of TIAs and ischemic strokes. Stroke with the following characteristics was diagnosed as perforator stroke: (a) The onset was closely related to the procedure, and the deficits were referable to the perforator territory adjacent to the vessel treated with a stent (ie, stroke developed immediately or soon after stent placement, and the patient had a lacunar syndrome at presentation). (b) With cerebral angiography, occlusion or more than 50% diameter reduction in the stent or large artery (diameter of 1 mm or larger) had been excluded. (c) Brain CT 24 hours after stroke revealed a new infarct in the perforator territory, which was adjacent to the vessel treated with a stent, or no new lesion (25).
On the basis of the patient's syndrome, identified with clinical findings and neuroimaging findings (angiography, transcranial Doppler ultrasonography, brain CT, and perfusion CT), the probable cause of complication was determined with consensus in a multidisciplinary meeting of some authors (K.H.D., T.W.L., W.J.J., B.D., and M.J., all of whom had 5 years or more of experience in neurologic evaluation in stroke).
Target-lesion thrombosis that manifested within 3 hours after stent placement was treated with intrathrombus thrombolysis with urokinase (Livzon Libao Biochemical & Pharmaceutical, Zhuhai, China). Currently, urokinase is a drug approved by the State Food and Drug Administration of our country. Spiral dissection was treated with additional stent placement. For perforator stroke and embolic stroke, the period of anticoagulation with nadroparin calcium was extended to 1 week. Vasospasm was treated with nimodipine infusion. In patients with ICH, antiplatelet therapy was withheld, heparin was neutralized by using protamine sulfate (Shanghai No. 1 Biochemical and Pharmaceutical), and blood pressure was controlled to be within 90–110/60–80 mm Hg.
Outcome of Stroke on Day 30
The patient's neurologic status at admission and at days 1 and 30 after surgery was assessed by an experienced neurologist (K.H.D., who had 20 years of experience in neurologic evaluation in stroke) with the NIHSS score. Stroke was considered "reversible" if the NIHSS score on day 30 was the same as or less than the preoperative NIHSS score, and stroke was considered "irreversible" if the NIHSS score on day 30 was greater than the baseline NIHSS score.
Statistical Analysis
All data were analyzed according to the intention-to-treat principle. The t test was used to assess the statistical difference between the age of patients with complications and the age of patients without complications. Fisher exact or 2 tests were used to assess statistical differences between rates for discrete variables. Stratification analysis with the Cochran-Mantel-Haenszel test was used to assess the significant relationship between the potential risk factor and complication, when there was a confounding effect of another factor. All reported probability values are two sided; differences with P < .05 were considered statistically significant.
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RESULTS |
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Antiplatelet Therapy
Perioperative noncompliance with antiplatelet therapy occurred in eight patients (patients 3, 7, and 10–15 in Table 2). These patients included one who inadvertently did not receive pretreatment with dual antiplatelet agents, six with ICH complications, and one who was suspected of having ICH (subsequently found to be contrast agent retention) who stopped the antiplatelet therapy immediately.
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In the six ICHs, four were symptomatic and two were asymptomatic. Five ICHs were detected immediately after stent placement, and one occurred on day 3, presumably from hyperperfusion syndrome (the blood pressure rebounded up to 150–160/90 mm Hg after withdrawal of nimodipine therapy on day 2).
In the six target-lesion thromboses, three were detected at surgery, one occurred on day 2, one occurred on day 3, and one occurred on day 14. Five target-lesion thromboses formed in the stent, and one formed within the side branch of the target lesion. The patient had a stenosis in the right intracranial VA across the stenotic ostium of the posterior inferior cerebellar artery and developed a right VA spasm during the delivery of the guiding catheter into the right VA. Although the VA spasm was resolved completely within 5 minutes with infusion of 0.2 mg nimodipine diluted with 10 mL of normal saline into the VA and withdrawal of the guiding catheter to the right subclavian artery, the patient had vertigo, nausea, nystagmus, and left hemianesthesia. Acute occlusion of the right posterior inferior cerebellar artery was considered as the cause and then was confirmed at angiography. A microcatheter was immediately advanced into this side branch, through which the 0.5 million units of urokinase (concentration, 40 000 U/mL of normal saline) was infused within 50 minutes. Complete recanalization was then obtained, followed by the complete disappearance of the syndrome. Intrathrombus thrombolysis with urokinase (total dose range, 0.2–1.0 million units) was immediately performed in the five other patients within several minutes to 1 hour from the onset of the syndrome, and complete patency was obtained in all within 2 hours from the onset, and patients returned entirely to the preprocedural status (ie, the postprocedural NIHSS score was the same as the preprocedural NIHSS score). No bleeding complications were documented at brain CT. These six events were all categorized as TIAs.
In the five perforator strokes, which had been described in detail previously (26), four occurred during the procedure, and one occurred 10 hours after stent placement. One patient developed right occipital and thalamic infarcts 12 hours after stent placement in the basilar artery. At angiography immediately after stent placement, one patient had asymptomatic spiral dissection of the VA proximal to the vessel treated with a stent; spiral dissection was treated with additional stent placement during the same procedure. The last patient with complications experienced five attacks of transient left hemiparesis on the next day after stent placement in the right MCA and 6 hours after withdrawal of nimodipine infusion. This event was presumably due to a vasospasm of a small artery, because repeated angiography revealed a widely patent vessel with a stent and good anterograde blood flow, and the patient had no further TIAs after resumption of treatment with the nimodipine infusion.
Thus, symptomatic and asymptomatic complications occurred in 17 and three patients (two ICHs, one dissection), respectively. Stroke occurred in 10 patients (5.9%, 10 of 169): five perforator strokes, one embolic stroke, and four symptomatic ICHs.
Outcome of Strokes on Day 30
In the four symptomatic ICHs, two were fatal strokes, one was a reversible minor stroke, and one was an irreversible minor stroke. In the six ischemic strokes, five were irreversible minor strokes and one was a reversible minor stroke. Thus, the frequency of irreversible minor stroke was 3.6% (six of 169), and the case fatality ratio was 1.2% (two of 169).
Statistical Analysis
Table 2 shows that complications in 19 patients occurred after the successful placement of a stent, and one occurred during the delivery of a guiding catheter. In the 19 patients in whom complications occurred after stent placement, the complications occurred in four (9.5%) after intracranial stents were placed in 42 lesions, and they occurred in 15 (12.1%) after coronary stents were placed in 124 lesions. There was no significant difference in the complication rate between the use of intracranial stents and the use of coronary stents (P = .268). The baseline characteristics of patients with and patients without complications and the angiographic characteristics of lesions with and lesions without complications were comparable (Tables 3 and 4). The rates of complications in stent placement in anterior (10.6%, 12 of 113) and posterior (11.8%, eight of 68) circulation lesions were similar and not significantly different (P = .81). Univariable analysis (Table 5) showed that perioperative noncompliance with antiplatelet therapy was significantly associated with target-lesion thrombosis, and the use of double stents for a single lesion and high-dose intraoperative heparin therapy were significantly associated with ICH. Results of stratification analysis (Table 6) revealed a significant correlation between the use of double stents for a lesion and ICH (P < .001). No significant correlation between intraoperative heparin dose and ICH was observed after adjustment of the analysis for the potential confounding effect of the stent pattern (a single stent for a lesion vs two [double stents] for a lesion) (P = .083).
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DISCUSSION |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONADVANCES IN KNOWLEDGEReferences |
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ICH could be fatal, and it caused two deaths in the series of patients in this study. ICH was detected immediately after stent placement in all but one of the six patients who had it, and these six patients included two with asymptomatic ICHs. These findings reiterate the importance of performing brain CT immediately after stent placement for intracranial stenosis. Hyperperfusion, vessel perforation, and vessel rupture are associated with ICH after stent placement in a cerebral artery (14,20,27). Currently, aggressive systemic blood pressure control remains the best available measure to prevent and treat hyperperfusion syndrome (14,28). Our study findings suggest that the use of double stents for treatment of a lesion is an independent risk factor for ICH. The most probable mechanisms include the following: The second (proximal) stent system may impinge onto the first (distal) stent during the procedure; the forward thrust of the distal end struts of the first stent may then perforate the arterial wall; and the eccentric advancement of the second stent system within the first expanded stent (advancement caused by the relatively tortuous course of the intracranial artery) may generate a forward drag on the major cerebral arteries, and this forward drag results in avulsion or rupture of the emanating fragile perforators. Although results of stratification analysis in this study revealed that high-dose intraoperative heparin (with which an activated clotting time of 250–300 seconds was obtained) was not an independent risk factor for ICH, interestingly, the low-dose intraoperative heparin regimen (with which a lower activated clotting time of 160–220 seconds was obtained) was not associated with increased target-lesion thrombosis. These data suggest that a randomized study may be warranted to investigate the optimal activated clotting time in stent placement for intracranial stenosis.
Target-lesion thrombosis is related to local intimal injury after angioplasty. Pretreatment with a combination of clopidogrel and aspirin before surgery has been recommended (19). Our results suggest the importance of periprocedural dual antiplatelet therapy because periprocedural noncompliance with antiplatelet therapy was associated with a higher frequency of target-lesion thrombosis.
About one-fourth of complications in our study were perforator strokes. Compromise of the perforators caused by angioplasty with or without stent placement may be associated with perforator stroke (29,30). Findings in our previous study indicated that patients with a preoperative perforator infarct adjacent to the stenotic segment have a higher frequency of perforator stroke after elective stent placement for intracranial stenosis (26). Thus, physicians should weigh carefully the risk against the benefit, when a patient with large-artery disease has a perforator event (TIA or stroke) and the pertinent perforators emanate from the target lesion. Currently, we only perform stent placement procedures in such patients when certain concurrent characteristics are present, as follows: (a) imminent main trunk occlusion (for example, a critical dissecting stenosis) or a high-grade symptomatic stenosis of the basilar artery without collateral vessels from bilateral posterior communicating arteries, (b) extensive perfusion failure referable to the stenosis evidenced at perfusion CT, and (c) failure of medical therapy.
Prudent patient selection, careful periprocedural medical treatment, and a highly skilled interventionist are all required to perform stent placement for intracranial stenosis with an acceptable stroke risk (18). Swift recognition and treatment of cerebrovascular complications are crucial for good patient outcomes. Our study results suggest that aggressive endovascular and medical therapy for cerebrovascular complications (11.8%, 20 of 169) can reduce the risk for stroke (5.9%, 10 of 169) or the fatal and irreversible stroke rate (4.7%, eight of 169).
Of note, there were some limitations of our study. First, the data are from a single center and may not be generalizable to other centers for reasons of selection bias, level of experience of the interventional neuroradiologist, and multidisciplinary care. Second, our study is not a randomized controlled trial in which stent placement with the best medical treatment or with balloon angioplasty alone were compared; therefore, we could not draw any conclusions about which option is better or worse. Last, in our study, the number of patients in whom double stents were used for a lesion is small so that the observed difference in the sample ICH rates might be due to sampling uncertainty or error; therefore, further study is needed. We have not discussed the long-term outcomes and restenosis rate in this article, because the aim of this study was to focus on the procedure-related cerebrovascular complications.
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ADVANCES IN KNOWLEDGE |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONADVANCES IN KNOWLEDGEReferences |
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FOOTNOTES |
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Abbreviations: ICH = intracranial hemorrhage • MCA = middle cerebral artery • NIHSS = National Institutes of Health Stroke Scale • TIA = transient ischemic attack • VA = vertebral artery
Authors stated no financial relationship to disclose.
Author contributions: Guarantors of integrity of entire study, all authors; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; manuscript final version approval, all authors; literature research, W.J.J., B.D., T.W.L.; clinical studies, all authors; statistical analysis, X.T.X; and manuscript editing, W.J.J., T.W.L., K.H.D.
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References |
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This article has been cited by other articles:
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  W.-J. Jiang, X.-T. Xu, M. Jin, B. Du, K.-H. Dong, and J.-P. Dai Apollo Stent for Symptomatic Atherosclerotic Intracranial Stenosis: Study Results AJNR Am. J. Neuroradiol., May 1, 2007; 28(5): 830 - 834. [Abstract] [Full Text] [PDF]
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