Endovascular treatment strategies for simultaneous bilateral anterior circulation occlusions in acute ischemic stroke: A single-center experience and systematic review of the literature

Abstract

Background

Bilateral and simultaneous occlusion of the anterior circulation is a rare event in patients with acute ischemic stroke. Although endovascular treatment is feasible and safe, the endovascular strategy to be used remains a subject of debate.

Objective

To assess the different endovascular strategies proposed for the treatment of a bilateral, simultaneous anterior circulation occlusion following acute ischemic stroke.

Methods

We present a retrospective study of the clinical and radiological records of all patients with a bilateral, simultaneous anterior circulation occlusion treated at our center between January 2019 and December 2022. Following the PRISMA guidelines, we also conducted a systematic review of the literature.

Results

Two patients with a bilateral and simultaneous middle cerebral artery occlusion were treated at our center during the study period. A TICI score ≥2b was obtained in 4 out of 4 occlusions. Modified Rankin Scale (mRS) at 90 days was 0 and 4, respectively. The literature review retrieved reports on 22 patients. The most frequent bilateral occlusion sites were internal carotid artery-middle cerebral artery. The clinical presentation was severe in most patients. A combined thrombectomy technique proved to have the highest number of first-pass recanalization. A TICI ≥2b was obtained in 95% of patients and an mRS ≤2 was found in 31.8% of patients.

Conclusions

In patients with bilateral and simultaneous occlusion of the anterior circulation, endovascular treatment using a combined technique appears to be rapid and effective. The clinical evolution of this patient population strongly depends on the severity of the onset symptoms.

Introduction

Multiple vessel occlusion occurs in approximately 10% of acute ischemic stroke (AIS) cases and is associated with a poor outcome. ¹ In most cases, the occluded vessels are located in the same vascular territory.^1,2 Bilateral and simultaneous occlusion of the anterior circulation is a very rare event, with a reported incidence of 0.34% in patients with AIS. ³ This clinical event is poorly described in the literature and different aspects of both the endovascular treatment and clinical evolution remain unclear. The presence of multiple large vessel occlusions exposes the patient to greater ischemic damage than a patient with a single large vessel occlusion. ¹ It has already been reported in the literature that endovascular treatment in this patient population has the same safety profile compared with patients with a single occlusion. ⁴ In such a patient population, it is crucial to achieve a rapid recanalization of the first site as a second occlusion of a contralateral large vessel still needs to be treated. For this reason, the thrombectomy technique used must be effective in as few steps as possible with a low risk of incomplete clot recovery to reduce the risk of thrombus fragmentation with the production of distal emboli.

We report here our experience of the treatment of bilateral and simultaneous occlusion by single femoral access and a combined thrombectomy technique comprising direct thromboaspiration (DTA) combined with stent-retriever thrombectomy (SRT). We also conducted a comprehensive systematic review of the literature to investigate the different strategies proposed and clinical outcomes in this rare patient population.

Methods

Patient population

We conducted a single-center, retrospective study of the clinical and radiological records of all patients presenting with AIS who were treated at our institution between January 1, 2019, and December 31, 2022. All patients who presented with bilateral and simultaneous occlusion of the anterior circulation were included in the study. Ethics approval was granted by the local institutional review board. Peri-procedural radiological images were retrospectively reviewed by two physicians with experience in the endovascular treatment of AIS (PM, GB) in a consensus reading. Patients’ medical records were reviewed to assess their clinical outcome.

Patients presenting with AIS were evaluated by CT scan, CT perfusion (RAPID software, iSchemiaView, Redwood City, California, USA) and CT angiography. Eligible patients received intravenous rt-PA after the CT scan.

Endovascular technique

According to our institutional protocol, endovascular procedures were performed with patients under general anesthesia using a bi-plane C-arm (Allura Clarity FD20, Philips Healthcare, Best, The Netherlands) via a single common femoral artery approach. Procedures were performed without heparinization. Arterial blood pressure was invasively monitored and amines were provided to maintain a mean arterial blood pressure of 90–100 mmHg throughout the procedure. A main catheter was placed in the internal carotid artery (ICA) and a combined endovascular treatment with SRT (CATCH MINI, Balt, Montmorency, France; TREVO 4 × 21 Striker, Kalamazoo, Michigan, USA) associated with DTA (Sofia 5, MicroVention, Aliso Viejo, California, USA) was performed. After recanalization, the thrombectomy system was placed in the contralateral ICA and the same thrombectomy procedure was performed. In the case of failure, the same procedure was repeated.

Literature review

Search strategy

Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for a scoping review, ⁵ we performed a systematic review of the English language literature using the Pubmed, Embase, World of Science, and Cochrane Library databases up to December 2022, as well as other methods such as Google Scholar, Prospero, and research papers mentioned in the references of articles and reviews of neuroradiology. Keywords and MeSH terms included “stroke,” “bilateral,” “dual thrombectomy” using also Boolean operators to articulate the research for reproducibility. Reference lists of selected articles and available non-systematic reviews were hand-searched for other potential citations. Duplicates were identified using EndNote software.

Study selection and data extraction

Two authors (GB and PB) independently screened titles and abstracts for articles reporting on AIS due to simultaneous bilateral anterior circulation occlusion treated by mechanical thrombectomy, with a non-restriction on the study design. This was followed by a full-text screening of any retained studies from the first screening step. Studies that included bilateral occlusions of the ICA or with simultaneous occlusion of the anterior and posterior circulation were excluded as they were characterized by a more dramatic clinical evolution. The following data were extracted from the full text of each study: year of publication; study design; patient characteristics; past medical history; treatment; stroke occlusion site; National Institutes of Health Stroke Scale (NIHSS) at admission; onset of symptoms; thrombectomy location, duration, and techniques used; number of thrombectomy passages; TICI score; and outcome (NIHSS or modified Rankin Score [mRS] or clinical evaluation). Bias risk assessment was evaluated by the Cochrane Collaboration Risk of Bias Tool. ⁶

Results

Case series

A total of 658 patients presenting with an AIS due to large-vessel occlusion were treated at our institution during the study period. Most were treated with a combined Stentriever technique in combination with aspiration catheter, according to our usual approach. Among these, we identified 2 patients (0.30%) with bilateral and simultaneous MCA occlusion (Table 1). Patient 1 presented with fluent aphasia and a NIHSS of 6, whereas patient 2 presented with an NIHSS of 29 and subsequent severe clinical deterioration with a Glasgow Coma Scale score of 5. In patient 1, both MCAs were recanalized at the first thrombectomy step, as was the case for the left MCA in patient 2 (Figures 1 and 2). In patient 2, thrombectomy of the right MCA required four thrombectomy passes. Duration of the procedures from inguinal puncture to revascularization of the second vessel was 45 min in patient 1 and 75 min in patient 2. Patient 1 showed an NIHSS of 0, whereas patient 2 had an NIHSS of 19 at 24 h after treatment. The mRS at 3 months was 0 and 4 for patients 1 and 2, respectively.

Table 1.

Patients’ baseline characteristics.

	Patient 1	Patient 2
Age	70–80	60–70
Gender	Female	Female
Risk factor	Atrial fibrillation	-
Medical therapy	Apixaban	-
Admission NIHSS	6	29
Glasgow Coma Scale	15	5
Occluded arteries	Right-M1 Left-M2	Right-M1 Left-M1
Ischemic core	Right + Left 0 ml	Right-32 ml Left-0 ml
Ischemic penumbra	Right + Left 77 ml	Right + Left 251ml
Onset to treatment	660 min	195 min.
Groin to recanalization	45 min	75 min
EVT techinique	Stentriever + aspiration	Stentriever + aspiration
First EVT side	Left	Left
Femoral access	Single	Single
N° of passes	Right-1 pass Left-1 pass	Right-4 passes Left-1 pass
TICI	Right-3 Left-3	Right-2b67 Left-3
NIHSS 24h	0	19
mRS 90 days	0	4

EVT, endovascular treatment; TICI, thrombolysis in cerebral infarction; mRS, modified Rankin Score; NIHSS, National Institutes of Health Stroke Scale; ml, milliliters; GCS, Glasgow Coma Scale; min., minutes.

Figure 1.

(A) CT angiography with bilateral middle cerebral artery occlusion; (B) RAPID summary with hypoperfusion of both cerebral hemispheres in the absence of ischemic core.

Figure 2.

(A) right M1 occluded; (B) right M1 post thrombectomy; (C) left M2 occluded; (D) left M2 post thrombectomy; (E-F) placement of stentriever and aspiration catheter in right middle cerebral artery; (G-H) placement of stentriever and aspiration catheter in left middle cerebral artery; (I-L) 48 h MRI, DWI b = 1000.

Literature review

We retrieved 707 papers for screening through the databases and 262 additional publications using other methods of identification. Subsequently, 12 studies with the appropriate report of outcomes of interest were retained for inclusion in the review (Figure 3). These comprised 10^3,7–15 case reports with a total of 12 patients, and two^4,16 retrospective multicenter case series with a total of 22 patients with bilateral simultaneous occlusion of the anterior circulation. Regarding Saad et al., ⁴ data from bilateral anterior circulation occlusion patients only could not be extracted. Patient and study characteristics are shown in Table 2. Fourteen of 22 patients (63.6%) had atrial fibrillation and 12/22 patients (54.5%) had hypertension. The most frequent occlusions were ICA-MCA in 8/22 patients and MCA-MCA (both M1 segments) in 2/22 patients. The clinical presentation was severe in most patients with a NIHSS >10 or clinical onset with coma. In 16/22 patients (72.7%), the endovascular procedure was performed under general anesthesia, whereas the type of anesthesia used was not reported for the remaining patients.

Figure 3.

PRISMA-P flow diagram.

Table 2.

Studies included in the literature review.

Authors/ Year	Design	Age	Sex	Risk factor	Stroke occlusion site	Admission NIHSS	Initial ASPECTS	i.v. rt-PA	GA	Time to thrombectomy	n° of femoral acces	EVT Duration	Thrombectomy techniques on the right	Thrombectomy techniques on the left	Thrombectomy passages	TICI	Post EVT NIHSS	mRS 90 days
Pop et al. 2013	Case report Case report	78 66	Female Female	Atrial fibrillation	MCA-ICA ICA-MCA	26 18	9 10	Yes Yes	Yes Yes	320 min. 280 min.	2 2	100 min. 82 min.	SRT SRT	SRT SRT	2–1 2–1	2b-3 2b-3	NR	0 3
Dietrich et al. 2014	Case report	72	Male	Atrial fibrillation and hypertension	M1- M1	NR	9	No	NR	NR	1	NR	Stent retriever	Stent retriever	1- multiple pass	NR	NR	NR
Ramos et al. 2018	Case report Case report	68 82	Female Female	Atrial fibrillation -Diabetes, hypertension,	M1-M2 M1-ICA	12 6	NR 10	NR yes	NR NR	480 min. 360 min.	NR NR	NR NR	SRT NR	SRT NR	1-multiple pass NR	3–0 3–3	NR NR	4 6
London et al. 2019	Case report	84	Female	Atrial fibrillation and hypertension	M1-M1	11	NR	Yes	Yes	244 min.	1	67 min.	DTA //SRT + DTA	SRT + DTA	multiple pass-1	NR	0	1
Storey et al. 2019	Case report	64	Female	Atrial fibrillation	M1-M2	NR	NR	NR	Yes	NR	1	NR	SRT + DTA	SRT + DTA	1 -1	3 - 3	NR	NR
Escalard et al. 2020	Case report	78	Female	Atrial fibrillation	M1-M1	Coma	NR	NR	Yes	220 min.	2	27 min.	SRT + DTA	DTA	1–1	3- 2c	4	2
Heyworth et al. 2020	Case report	69	Female	Atrial fibrillation	M1-M1	12	NR	NR	NR	285 min.	1	30 min.	SRT + DTA	SRT + DTA	1–1	3- 3	1	NR
Khanna et al. 2021	Case report	65	Female	Hypertension	M1 -M2	NR	NR	NR	Yes	NR	2	NR	DTA	DTA	1–1	3–3	NR	0
Wu et al. 2021	Case report	NR	NR	Atrial fibrillation	M1-M1	28	7–10	NR	NR	229 min.	2	35 min.	DTA	DTA	1-multiple pass	2B- 2B	NR	5
Kaesmacher et al. 2020	Case series of 10 patients	75.5 (IQR 61–86.5)	f 60% (6/10)	Atrial fibrillatio 50% ; Diabetes mellitus 10%; Arterial hypertension 70%	M1-M1 = 2; M2-M2 = 2; M1-M2 = 1 ; ICA-M1 = 4; ICA-M2 = 1	21 (IQR 5.5–30)	7–10	20% (2/10)	Yes (100%)	227 min. (161.5–331)	NR	129 min (IQR, 89.5–201)	NR	NR	2 (IQR, 1–4) /2 (IQR, 1–3)	≥ 2b 95.2%	8 (IQR, 2–20)	20% mRS 0–2
Joyce et al. 2022	Case report	95	Female	Hypertension Atrial fibrillation Hyperlipidemia	M1-M1	13	8	NR	No	NR	2	28	DTA	DTA	1–1	2c-3	NR	6
Saad et al. 2022	Case series of 15 cases	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-

NR, not reported; SRT, stent-retriever thrombectomy; DTA, direct thromboaspiration; GA, general anesthesia; IQR, interquartile range; min., minutes; TICI, thrombolysis in cerebral infarction ; MCA, middle cerebral artery; ICA, internal carotid artery; EVT, endovascular treatment; mRS, modified Rankin Score.

When considering the case reports,^3,7–15 mean time to thrombectomy was 302 min (range 220–480 min) in 8/12 patients. For Kaesmacher et al., ¹⁶ the median time from onset to thrombectomy was 246.5 min and the median procedural time from groin puncture to successful reperfusion of the second site was 129 min. In 6/10 patients where it was specified, endovascular treatment was performed via bilateral femoral access. When described, the thrombectomy techniques used were stand-alone SRT (8/24 sites), a combination of DTA and SRT (6/24 sites), and stand-alone DTA (8/24 sites). First-pass recanalization was achieved in 6/6 procedures for the combined technique (100%), in 4/8 (50%) procedures for stand-alone SRT, and in 6/8 for stand-alone DTA (75%). When reported, TICI 2b-3 was obtained in 19/20 occlusions (95%) in the case report series and in 95.2% of patients in the multicenter retrospective case series. ¹⁶ Seven of 22 patients presented an mRS 0–2 (31.8%) at 90 days. For 3/22 (13.6%) patients, the mRS at 90 days was not reported, but patients had a positive evolution compared to the clinical onset. All included publications were retrospective case reports with an overall high risk of bias.

Discussion

This systematic review of the literature showed that a combined SRT and DTA technique achieved the highest number of first-pass effects in the treatment of bilateral and simultaneous occlusions of the anterior circulation. The effectiveness of such a technique in this rare category of patients was also demonstrated in our clinical practice. Of note, although a bilateral femoral access can help to reduce the time of endovascular treatment, a single femoral access was sufficient to obtain a good angiographic result in a reasonable time window. The clinical evolution of the patient was highly dependent on the severity of the clinical onset and the extent of the ischemic core. The presence of multiple large vessel occlusions exposes the patient to greater ischemic damage than a patient with a single large vessel occlusion. ¹ This occurs both because more vascular territories are involved and as the function of the polygon of Willis or pial collaterals may be impaired. ¹⁶ However, Saad et al. ⁴ showed that in appropriately selected patients with multiple vessel occlusion, endovascular treatment has the same safety profile and outcome as patients with single occlusion. In addition, Kaesmaker et al. ¹ showed that patients with multivessel occlusion did not show a higher prevalence of sICH than patients with single vessel occlusion.

Our literature review retrieved only 10 case reports^3,7–15 and two retrospective multicenter series^4,16 of bilateral simultaneous MCA-MCA or MCA-ICA occlusion, which suggests that this is a rare event, involving approximately 0.34–0.35% of patients.^3,16 These data match with the experience of our center where the incidence was 0.30%. Cardioembolic origin or paradoxical embolism are the most likely causes, given the multi-territoriality of occlusions. It could be argued that a thrombus able to embolize in different territories is a fragile clot that can therefore fragment, e.g., under the effect of high blood pressure induced by AIS.^1,17 However, the combined technique of SRT in association with DTA has also been shown to be effective in the presence of clots prone to fragment.^18–24 The association of DTA with SRT reduces the risk of ineffectiveness of the endovascular procedure and thus the risk of clot fragmentation with embolization into new territories. ¹⁹ Indeed, the latter would lead to a lengthening of the procedure time, in addition to having a negative impact on the clinical evolution of the patient.

The first-pass effect has been shown to be an independent factor of a favorable outcome for patients affected by AIS. ²⁵ In this patient population, a first-pass revascularization is crucial to allow the contralateral occlusion to be managed as soon as possible. Given the severity of the clinical condition, endovascular treatment is often performed under general anesthesia in this patient population as shown in the literature review (16/22 patients treated under general anesthesia). Therefore, it is important to emphasize that the maintenance of an adequate arterial blood pressure is mandatory for a good clinical outcome ²⁶ as it supports the functionality of collateral vascularization. In the retrospective multicenter case series, ¹⁶ only 20% of patients showed an mRS 0–2 at 90 days, although the Alberta Stroke Program Early CT Score (ASPECTS) on admission was between 7 and 10 for both vascular territories. Interestingly, a median of two thrombectomy passes for each occlusion and a median procedural time of 129 min for revascularization of the second site were recorded in this study.

Although a bilateral femoral access is technically possible^3,9,12,14 and may allow bilateral revascularization in a short time window, the clinical evolution of patients was not strictly related to this type of procedure. Indeed, our review does not show a significant difference in the outcome of patients treated with a single or double femoral approach. To perform a thrombectomy with double femoral access would require the presence of two experienced operators, which is not always possible. In addition, the severity of the clinical onset, the volume of the ischemic core at admission,^27,28 and the promptness of the revascularization procedure ²⁵ in this category of patients are crucial for the clinical evolution. The choice of which occluded site should be recanalized first may be influenced by several anatomo-physiological and clinical considerations, but it would probably be appropriate to treat first the occlusion site that leads to the most severe component of the patient's clinical condition.

Study limitations

Our study has some limitations. First, this is a single-center experience with a small number of patients, thus demonstrating the rarity of the event. Second, the main limitation is the design of the included studies, given that most are case reports with a high risk of bias. Third, it is also possible that there is a publication bias in favor of studies with a positive treatment outcome. Finally, an additional limitation is the lack of clinical and procedural data, which are useful to clarify various aspects of patient management.

Conclusions

In patients with bilateral and simultaneous occlusion of the anterior circulation, endovascular treatment using a combined technique with DTA and SRT appears to be rapid and effective. The clinical evolution of this patient population strongly depends on the severity of the onset symptoms, the extent of the ischemic lesion, but also on the promptness of the revascularization procedure. Further studies and data are needed to better understand the implications of this rare clinical occurrence.

Abbreviations

AIS

acute ischemic stroke

DTA

direct thromboaspiration

ICA

internal carotid artery

NIHSS

National Institutes of Health Stroke Score

MCA

middle cerebral artery

mRS

modified Rankin Score

SRT

stent-retriever thrombectomy

TICI

thrombolysis in cerebral infarction;