Direct angioplasty for acute ischemic stroke due to intracranial atherosclerotic stenosis-related large vessel occlusion

Abstract

Background

Intracranial artery atherosclerotic stenosis (ICAS) is among the causes of intracranial large artery occlusion (LVO). The optimal treatment strategy for patients with ischemic stroke due to ICAS-related LVO remains unclear. In this retrospective case series, we discussed our experience with direct angioplasty as frontline therapy for ICAS-related LVO.

Methods

We extracted data for patients who had a known pre-existing ICAS and undergone direct angioplasty as frontline therapy for ICAS-related LVO in the anterior circulation at our institution between January 2019 and December 2019. We analysed procedural details, the degree of reperfusion, functional outcomes, and complications. Successful reperfusion was defined as a modified Treatment in Cerebral Ischemia (mTICI) score of 2 b − 3. Functional outcomes at 90 days were assessed using modified Rankin Scale (mRS) scores (good outcome: mRS of 0–2).

Results

We analysed data for five patients (mean age: 51.6 ± 11 years). The mean time from symptom onset to recanalization was 371 ± 38.6 min. Occlusions involved the first segment of the middle cerebral artery in four patients and the intracranial internal carotid artery in one patient. Successful reperfusion was achieved in four (80%) patients. The remaining patient (20%) underwent intracranial stenting as rescue therapy, achieving a final mTICI of 2a. No re-occlusion was observed on follow-up images. Four patients (80%) achieved good outcomes at 90 days. There were no cases of symptomatic intracranial hemorrhage, although asymptomatic intracranial haemorrhage was observed in one patient.

Conclusion

Direct angioplasty may represent an alternative treatment strategy in patients with acute ischemic stroke due to known ICAS-related LVO.

Introduction

Since the publication of findings from five randomised clinical trials, endovascular treatment has become standard for patients with acute ischemic stroke due to large vessel occlusion (LVO).^1–5 Severe atherosclerotic stenosis of the intracranial arteries (ICAS) is among the major causes of large intracranial artery occlusion in Asian and Hispanic populations and accounts for approximately 12–30% of all strokes due to LVO.^6–8 However, the optimal treatment strategy for patients with ischemic stroke due to ICAS-related LVO remains unclear.⁹ ICAS-related LVO is often refractory to stent-retriever thrombectomy.¹⁰ Rescue therapy such as angioplasty and/or stenting is usually necessary for successful reperfusion in patients with ICAS-related LVO.⁹ We assumed that skipping thrombectomy prior to angioplasty may lead to faster recanalization and improved outcomes. In the present study, we aimed to analyse data for five patients with acute ischemic stroke due to ICAS-related LVO, focusing on indications of angioplasty as frontline therapy in these patients.

Methods

The present study was approved by the appropriate institutional ethics committee. All patients provided written informed consent.

All patients undergoing endovascular treatment for ischemic stroke at a single institution were prospectively registered in an electronic database. For this study, we extracted data for patients with acute ischemic stroke due to ICAS-related LVO in the anterior circulation who had undergone angioplasty as frontline therapy between January 2019 and December 2019. All patients had a diagnosis of severe ICAS as determined via previous magnetic resonance angiography (MRA). ICAS-related LVO was defined as an occlusion located at the site of ICAS on previous MRA. Direct angioplasty was indicated when computed tomography (CT) angiography or digital subtraction angiography (DSA) revealed occlusions with short thrombus (clot burden score (CBS): 7 to 10).¹¹

The following data were extracted and analysed: demographic characteristics, baseline National Institutes of Health Stroke Scale (NIHSS) scores, baseline Alberta Stroke Program Early CT Scores (ASPECTS), collateral status, CBS, previous stroke, intravenous thrombolysis (IV), time from stroke onset to groin puncture, and procedure duration.

Technical procedures

All interventional procedures were performed under conscious sedation without heparinisation. A microcatheter was navigated with a guidewire (Traxcess 14, Microvention, Aliso Viejo, CA, USA) to the distal lumen of the occlusion site. Following angiography performed, each patient underwent reperfusion therapy using a semi-compliant intracranial balloon catheter (Neuro RX, Sinomed, Tianjin, China). Balloon sizes were determined based on the surgeon’s discretion. The diameter of the balloon should approximate the lesser of the vessel diameters just proximal and distal to the occlusion. The balloon was inflated under nominal pressure for 30 seconds. Patients then received an intra-arterial infusion of tirofiban (Grandpharma, Wuhan, China), a glycoprotein IIb/IIIa inhibitor. Tirofiban was injected at a rate of 1.5 ml/min through the guiding catheter. The total dosage of tirofiban typically ranged from 0.5 mg to 1.0 mg during the procedure.¹² DSA was performed immediately after the infusion and was repeated 20 minutes later to assess recanalization. Procedures were completed when we observed successful reperfusion without the tendency for re-occlusion. Stent-retriever thrombectomy or intracranial stenting was performed as a rescue therapy in cases of unsuccessful recanalization. IV tirofiban was administered at a maintenance dose of 0.25 mg/h for 24 h. Aspirin (100 mg/day) and clopidogrel (75 mg/day) were administered 4 hours prior to the discontinuation of tirofiban.

Outcomes and complications

The degree of reperfusion was assessed on the last DSA angiogram, based on the modified Treatment in Cerebral Ischemia (mTICI) score. Successful reperfusion was defined as an mTICI score of 2 b − 3 on the last angiogram. Functional outcomes at 90 days were assessed using modified Rankin Scale (mRS) scores. Scores of 0 to 2 were considered indicative of good outcomes. Complications included vessel perforation, arterial dissection, intracranial haemorrhage, progression of stroke, embolism in new territories, and recurrent stroke in the same territories at the 90-day follow-up. Intracranial hemorrhage was assessed via non-contrast CT 24 h following the procedure. Symptomatic hemorrhage was defined as an increase of 4 or more points on the NIHSS.

Statistical analysis

Data were analysed using descriptive statistics. Continuous variables were expressed as the mean ± standard deviation or as medians and quartiles. Categorical variables were expressed as absolute values (i.e., number of patients) and relative frequencies (percentages).

Results

Patient characteristics

A total of 192 patients with ischemic stroke underwent endovascular treatment between January 2019 and December 2019. LVO due to ICAS in the anterior circulation was observed in 12.8% (19/149) of patients. Among them, five patients (mean age: 57 ± 11.2 years) underwent angioplasty as frontline therapy and were included in the present series. All four patients (80%) with previous stroke exhibited preoperative mRS scores of 0. Occlusions were located on the left side in four patients (80%). Occlusions involved the first segment of the middle cerebral artery (M1) in four patients (80%) and the intracranial internal carotid artery in one patient (20%). The mean baseline NIHSS score was 17.6 (range: 11–26). Two patients received intravenous thrombolytic agents prior to endovascular treatment. The mean time from symptom onset to recanalization was 304 ± 62.6 min. The duration of the procedure ranged from 30 to 160 min. Detailed patient characteristics are presented in Table 1.

Table 1.

Clinical characteristics.

Patient No.	1	2	3	4	5
Occlusion location	Left M1	Right M1	Left M1	Left M1	Left ICA
Hypertension	Yes	Yes	Yes	Yes	Yes
Hypercholesterolemia	Yes	No	No	No	No
Diabetes mellitus	No	No	No	Yes	Yes
Previous stroke	Yes	Yes	No	Yes	Yes
Baseline NIHSS	16	11	20	26	15
Baseline ASPECTS	10	7	9	9	10
Intravenous thrombolysis	No	Yes	No	No	Yes
Time from onset to groin puncture (min)	320	295	390	215	300
Time from puncture to recanalization min)	30	40	45	160	60

M1, first segment of the middle cerebral artery; ICA, internal carotid artery; NIHSS, National Institutes of Health Stroke Scale; ASPECTS, Alberta Stroke Program Early CT Score.

Outcomes and complications

Successful reperfusion was achieved in four patients (80%), two patients (40%) exhibited complete reperfusion (mTICI: 3). The patient who did not exhibit successful reperfusion following angioplasty underwent stenting as rescue therapy (final mTICI: 2a). Good outcomes were observed in two patients (40%) at the 90-day follow-up. Four patients (80%) achieved favourable outcomes (mRS: 0–3). We observed no recurrence of ischemic stroke among these five patients, although asymptomatic intracranial haemorrhage was noted in one patient (20%). No other complications were reported (Table 2).

Table 2.

Outcomes and complications.

Patient No.	1	2	3	4	5
mTICI score	3	2b	2b	2a	3
Rescue therapy	No	No	No	Stenting	No
Asymptomatic hemorrhage	No	No	No	Yes	No
mRS score at 90 days	0	1	3	4	3

mTICI, modified Treatment in Cerebral Ischemia; mRS, modified Rankin Scale.

Case illustration

Case 1

An adult male (patient No. 1) presented 5 hours after the onset of left hemispheric stroke and aphasia. His baseline NIHSS and ASPECTS scores were 16 and 10, respectively. Three months earlier, he had experienced a minor stroke accompanied by weakness in his right limbs. MRA performed 3 months prior to admission revealed severe stenosis in the left M1 (Figure 1(a)). DSA during the more recent attack indicated an occlusion of the left M1 with good collaterals. Retro-flow reconstituted the distal portion of M1 (Figure 1(b)), suggestive of ICAS-related LVO. Direct angioplasty was performed using a balloon catheter (Neuro RX 2.0*15, Sinomed, Tianjin, China) (Figure 1(c)). Following angioplasty, his mTICI score was 3 (Figure 1(d) to (f)). The time from onset to groin puncture was 320 min, while the duration of the procedure was 30 min. Tirofiban was administered for 24 h, followed by aspirin and clopidogrel. The patient recovered immediately after the procedure, and his mRS score at 90 days was 0. No recurrence of stroke or transient ischemic attack occurred within this 90-day period.

Figure 1.

Images of case 1. (a) MRA performed 3 months prior to admission revealed severe stenosis in the left M1. (b) DSA during the more recent attack indicated occlusion of the left M1 with good collaterals. Retro-flow reconstituted the distal portion of M1. (c) Direct angioplasty was performed using a balloon catheter. (d–f) Angioplasty achieved an mTICI score of 3. MRA, magnetic resonance angiography; M1, first segment of the middle cerebral artery; DSA, digital subtraction angiography; mTICI: modified Treatment in Cerebral Ischemia.

Case 2

An adult male (patient No. 2) presented 6.5 hours after the onset of right hemispheric stroke. His baseline NIHSS and ASPECTS scores were 11 and 7, respectively. Two months earlier, he had experienced a minor stroke presented with weakness in his left limbs. MRA performed 2 months prior to admission revealed severe stenosis in both M1 (Figure 2(a)). DSA during the more recent attack indicated an occlusion of the right M1 (Figure 2(b)), suggestive of ICAS-related LVO. Direct angioplasty was performed using a balloon catheter (Neuro RX 1.5*10, Sinomed, Tianjin, China) (Figure 2(c)). Following angioplasty, his mTICI score was 2 b (Figure 2(d) to (f)). The time from onset to groin puncture was 295 min, while the duration of the procedure was 40 min. Tirofiban was administered for 24 h, followed by aspirin and clopidogrel. The patient’s mRS score at 90 days was 1. No recurrence of stroke or transient ischemic attack occurred within this 90-day period.

Figure 2.

Images of case 2. (a) MRA performed 2 months prior to admission revealed severe stenosis in both M1. (b) DSA during the more recent attack indicated occlusion of the right M1. (c) Direct angioplasty was performed using a balloon catheter. (d–f) Angioplasty achieved an mTICI score of 2 b. MRA, magnetic resonance angiography; M1, first segment of the middle cerebral artery; DSA, digital subtraction angiography; mTICI: modified Treatment in Cerebral Ischemia.

Discussion

In the present study, we summarised data for patients with ischemic stroke due to ICAS-related LVO who had a known pre-existing stenosis in their artery and undergone direct angioplasty as frontline therapy at our institution. The rate of successful reperfusion following direct angioplasty was high, and no severe complications were observed.

ICAS-related LVO occurs when fixed intracranial stenosis is observed at the site of occlusion following thrombectomy.¹³ Although the diagnosis of ICAS-related LVO remains challenging, the presence of progressive symptoms and/or a history of atherosclerotic disease may aid in diagnosis. Eighty percent of patients in our study had previously experienced a stroke, and all patients exhibited intracranial artery stenosis on previous MRA images. Furthermore, more recent DSA images revealed occlusions at the site of previous ICAS in our patients. Such findings were used to make definitive diagnoses of ICAS-related LVO.

Current guidelines recommend stent-retriever or aspiration thrombectomy for LVO.¹⁴ However, the optimal treatment strategy for ICAS-related LVO remains to be determined, given that performing thrombectomy first may lead to thrombus removal without dilation of the atherosclerotic plaque. Furthermore, thrombectomy may lead to injury of the intima, resulting in immediate re-occlusion.¹⁵ Indeed, only a portion of patients with ICAS-related LVO achieve successful reperfusion following thrombectomy.¹⁶ Previous studies have noted that more than one third of patients exhibit immediate re-occlusion following thrombectomy, which typically necessitates rescue therapy.¹⁷ Jia et al.¹⁸ reported that 63.8% of patients accepted rescue therapy following re-occlusion, while another multicentre prospective cohort study reported that rescue therapy was performed in 71.7% of patients.¹⁹ When performed as rescue therapy, angioplasty and/or stenting can reduce the risk of re-occlusion in patients with ICAS-related LVO, without increasing the risk of intracranial haemorrhage. Although the final rate of successful reperfusion was similar, previous studies have indicated that clinical outcomes are poorer among patients with ICAS than among those without ICAS.^20,21 This finding may be attributable to the long procedure duration in patients with ICAS: One study noted that mean procedure times (155 min vs. 40 min) were significantly longer in patients with ICAS-related LVO undergoing rescue stenting or angioplasty.²² Skipping thrombectomy prior to angioplasty may lead to faster recanalization and improved outcomes. In our study, the procedure duration was under 60 min in most cases, similar to findings reported in a previous study.²³

Several studies have highlighted the safety and efficacy of angioplasty as rescue treatment following thrombectomy in patients with ICAS-related LVO.^24,25 Use of a balloon catheter for angioplasty can increase the diameter of the lumen lesion and reduce the risk of intra-procedure re-occlusion. Tokunaga et al.²⁶ reported that direct angioplasty with or without intra-arterial thrombolysis for acute LVO is associated with a low risk of haemorrhagic complications. Nakano et al.²⁷ also reported a high rate of recanalization and good outcomes in patients with LVO who had undergone direct angioplasty. In accordance with these findings, successful recanalization was achieved in 80% of our patients without severe complications, with 40% exhibiting good outcomes.

A potential disadvantage of direct angioplasty for ICAS-related LVO is the risk of distal embolisation.²⁸ Angioplasty can fragment relatively long thrombus, which can then migrate distally. To avoid distal embolization, thrombus length should be evaluated prior to angioplasty. A CBS of 7–10 on CT angiography indicates a short thrombus and has been associated with good outcomes following endovascular treatment.¹¹ Thrombus length can also be assessed using DSA. Thrombus length is defined as the distance between the most distal filling of the blocked artery and the most proximal filling of the closest collateral vessel.²⁹ When collaterals are absent, the distal margin of the thrombus is defined based on the proximal retrograde flow of contrast on a microcatheter angiogram. Long thrombus has also been associated with poor clinical outcomes.³⁰ Thus, patients with longer thrombus were excluded from the present study and underwent thrombectomy first. No cases of distal embolization were observed in our series.

The present study possesses some limitations of note, including its small sample size. In addition, although we extracted data from a prospective database, the case series was retrospective in nature. As such, we were unable to examine follow-up images or the degree of long-term reperfusion. Further randomised studies are required to determine the optimal treatment strategy for patients with ischemic stroke due to ICAS-related LVO.

Conclusion

Direct angioplasty may represent an alternative treatment strategy in patients with acute ischemic stroke due to known ICAS-related LVO.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Ethics approval

This study was approved by the ethics committee of The First Affiliated Hospital of Harbin Medical University.

Declaration of conflicting interests

The author(s) received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Huaizhang Shi https://orcid.org/0000-0003-3150-6234