Article Text


Original research
Anterior cerebral artery embolism during thrombectomy increases disability and mortality
  1. Vanessa Chalumeau1,
  2. Raphaël Blanc1,
  3. Hocine Redjem1,
  4. Gabriele Ciccio1,
  5. Stanislas Smajda1,
  6. Jean-Philippe Desilles1,
  7. Daniele Botta1,
  8. Simon Escalard1,
  9. William Boisseau1,
  10. Benjamin Maïer1,
  11. Julien Labreuche2,
  12. Mickaël Obadia3,
  13. Michel Piotin1,
  14. Mikael Mazighi1,4,5,6
  1. 1 Departement of Interventional Neuroradiology, Rothschild Foundation, Paris, France
  2. 2 Department of Biostatistics, Hospital Center Regional University De Lille, University of Lille, Paris, France
  3. 3 Department of Neurology, Rothschild Foundation, Paris, France
  4. 4 Denis Diderot University, Paris, France
  5. 5 INSERM U 1148, Laboratory of Vascular Translational Science, Bichat Hospital, Paris, France
  6. 6 DHU Neurovasc, Paris, France
  1. Correspondence to Dr Vanessa Chalumeau, Service de Neuroradiologie Interventionnelle Fondation, ophtalmologique Adolphe de Rothschild, Paris 75019, France; chalumeau.vanessa{at}


Objective During thrombectomy, thromboembolic migration in previously unaffected territory may occur and is not systematically notified. We report our data on the incidence, predictors, and clinical outcome of anterior cerebral artery emboli (ACAE).

Methods From a prospectively collected thrombectomy database of consecutive patients with anterior circulation stroke between January 2012 and December 2016, 690 angiographic images were analyzed to assess ACAE. The primary outcome was a favorable outcome, defined as a 3 month modified Rankin Scale score of 0–2 or equal to the pre-stroke score.

Results ACAE occurred in 65 patients (9.4%; 95% CI 7.2% to 11.6%). Internal carotid artery occlusion (tandem or terminal), Alberta Stroke Program Early CT Score <7, increasing number of passes, and use of stent retriever alone (compared with distal aspiration alone or combined with stent retriever) were found to be independent predictors of ACAE. Compared with patients without ACAE, patients with ACAE had lower rates, with an adjusted OR (95% CI) of 0.48 (0.25 to 0.92; P=0.027) for favorable outcome and 0.49 (0.25 to 0.96; P=0.038) for early neurologic improvement. ACAE was significantly associated with a higher mortality (adjusted OR 1.93; 95% CI 1.03 to 3.61; P=0.039) and intracranial hemorrhagic complications (adjusted OR 2.45; 95% CI 1.33 to 4.47; P=0.004). Despite a successful reperfusion modified Thrombolysis in Cerebral Infarction score of 2b–3 at the end of the procedure, a favorable outcome was reached in 30% of patients with ACAE compared with 52.4% in the other patients (OR 0.39; 95% CI 0.19 to 0.78; P=0.008).

Conclusions Procedural ACAE was not an uncommon condition, and was associated with increased mortality and disability rates, regardless of the success of reperfusion.

  • stroke
  • thrombectomy
  • complications
  • embolic
  • angiography

Statistics from


Since the validation of endovascular management in acute ischemic stroke,1–6 more patients are now eligible for mechanical thrombectomy (MT). Stent retrievers (SRs)1–8 and modern aspiration catheters, used alone9–12 or combined,8 9 11–14 achieve successful reperfusion rates in a large majority of cases. However, undesirable events, including thromboembolic migration in previously unaffected anterior cerebral artery (ACA) branches, may occur during the procedure. Although studies have evaluated the feasibility and efficacy of ACA revascularization,15 16 limited data are available on the impact of thromboembolic migration in previously unaffected ACA territories on outcome. With a frequency ranging from 3.5% to 11.4%,15 17 anterior cerebral artery emboli (ACAE) may be responsible for new ischemic lesions in a third of patients. However, its clinical relevance remains a source of debate.18 The purpose of this study was to evaluate the impact on functional outcome of procedure related ACAE.


Study population

Patients were identified from a prospectively gathered database of 812 acute ischemic stroke patients treated with MT between January 2012 and December 2016 in one comprehensive French stroke center. Patients with complete occlusion of the intracranial internal carotid artery (ICA) or the middle cerebral artery (MCA), confirmed on DSA and eligible for MT, were included (n=788). Angiographic images were analyzed to assess per procedural emboli in ACA branches. Patients with concomitant ACA occlusion or agenesis on prior diagnostic imaging or on a pretreatment contralateral carotid angiogram, and patients with insufficient imaging material were excluded (n=98). The study was approved by the local ethics committee.

Data collection and definitions

Patient demographics, vascular risk factors, previous antiplatelet and anticoagulation therapy, time from symptom onset (or from patient last seen normal), arterial occlusion site and lateralization, National Institutes of Health Stroke Scale (NIHSS) at admission,  administration and time from IV thrombolysis were collected prospectively. Stroke etiology was defined according to the Trial of ORG 10172 in Acute Stroke Treatment classification.19 The findings on baseline MRI for the Alberta Stroke Program Early CT Score (ASPECTS) were reported.

Procedure modalities, such as general anesthesia, use of balloon guide catheter, adjuvant balloon and/or stent angioplasty, type of device used, number of device passes, and time from groin puncture to reperfusion were also collected. The type of device used was divided into three subgroups: aspiration component alone, SR alone, or a combination of both devices during the procedure. Reperfusion results were reported using the modified Thrombolysis in Cerebral Infarction (mTICI) score. Successful reperfusion was defined as a mTICI score of ≥2b.

ACAE was defined as the occurrence of thromboembolic migration in a previously unaffected ACA territory after at least one pass of thrombectomy. A systematic pretreatment contralateral carotid angiogram confirmed the initial patency of both ACAs in the case of ICA terminus occlusion. The location of the occlusion was assessed on angiographic images and categorized following the anatomic segmentation of the ACA as A2 segment (between the anterior communicating artery and the genu of the corpus callosum), A3 segment (curving around the genu of the corpus callosum), and callosomarginal artery or distal branches.

Post-procedure clinical evaluation was defined using NIHSS at 24 hours. For each patient, the final mTICI score was retrospectively assessed by a neurointerventionalist blinded to the clinical outcome. Functional outcomes at admission and at 90 days were determined using the modified Rankin Scale (mRS) score. Mortality was defined as death occurring within 90 days.

Hemorrhagic and extended ischemic complications were assessed with follow-up CT scans and MRI obtained at 24–48 hours. Intracranial hemorrhage (ICH) was classified according to the European Cooperative Acute Stroke Study (ECASS) criteria.20 Symptomatic ICH (sICH) was defined as any ICH with an increase of at least 4 points on the NIHSS within 24 hours, or resulting in death.

Outcome measures

The primary outcome measure was a favorable outcome, defined as a 90 day mRS score of 0–2 or equal to the pre-stroke mRS score. Secondary outcomes included successful reperfusion (mTICI 2b/3 at the end of the procedure), complete reperfusion (mTICI 3 at the end of the procedure), excellent outcome (90 day mRS score of 0–1 or equal to pre-stroke score), early neurological improvement (NIHSS score of 0–1 at 24 hours or a decrease of 8 or more points in NIHSS score in 24 hours), all cause mortality at 90 day, any ICH, and sICH.

Endovascular procedure

A thrombectomy strategy was chosen at the interventionalist’s discretion using direct aspiration, an SR alone, or a combined technique in the first instance and for the remaining procedure. Accorded to the definition of a direct aspiration first pass technique (ADAPT)11 and considering the time window and possible risks, the operator was the decision maker in aborting or repeating several maneuvers with the same or combined devices, if reperfusion could not be achieved. Combined techniques also included the Solumbra techniques.13 During the procedure, ACAE occurrence may change the strategy and lead to rescue thrombectomy. In this case, the operator could use the same or different devices.

Statistical analysis

Continuous variables are expressed as means±SD or medians (IQR), and categorical variables as number (percentage). Normality of distribution was assessed using histograms and the Shapiro–Wilk test. The rate of ACAE was calculated with its 95% binomial CI. Bivariate comparisons for baseline, treatment characteristics, and outcomes between the two study groups (patients with and without ACAE) were made using the χ2 test (or Fisher’s exact test when the expected cell frequency was <5) for categorical variables, the Student’s t test for Gaussian continuous variables, and the Mann–Whitney U test for non-Gaussian continuous and ordinal categorical variables, as appropriate.

To assess the independent predictors of ACAE, all baseline and treatment characteristics with P<0.10 in the bivariate analyses were entered into a forward stepwise multivariable logistic model using an entrance criteria of P<0.10. The characteristics that remained in the forward stepwise logistic regression model were subsequently used to adjust the comparisons in outcomes between the two study groups in separate multivariable logistic models; adjusted OR were derived from these models as effect sizes using absence of ACAE as the reference group. Before developing the multivariable prognostic model of ACAE, we examined the log linearity assumption for continuous characteristics (irrespective of previous bivariate comparisons) using restricted cubic spline functions,21 as well as the absence of co-linearity between candidate predictors by calculating the variance inflation factors.22 We examined the performance of the final model in terms of calibration using the Hosmer–Lemeshow goodness of fit test and discrimination by calculating the c statistic.21

Due to the presence of missing data for clinical outcomes (favorable/excellent outcome and mortality, 3.0%; early neurological improvement, 15.8%; ICH complications, 8.3%), we performed sensitivity analyses using a multiple imputation approach to handle missing values.

Finally, we assessed the impact of ACAE on clinical efficacy and safety outcome (favorable and excellent outcomes, early neurological improvement, mortality, and any ICH) according to successful reperfusion status using logistic regression models, including the interaction term between reperfusion status and ACAE. Statistical testing was done at the two tailed α level of 0.05. Data were analyzed using SAS software V.9.3 (SAS Institute, Cary, North Carolina, USA).


Patient and treatment characteristics are described in table 1 for the overall study sample and according to the presence or absence of ACAE. Mean age of the 690 included patients was 67.1 years (SD 15.1), 362 (52.5%) were men, median baseline NIHSS score was 17 (IQR, 12 to 21), and the median time from symptom onset to groin puncture was 250 min (IQR 205 to 305). SR was used as the exclusive reperfusion technique in 141 patients (20.4%), the aspiration component alone in 278 (40.3%) patients, and the combined techniques in 271 (39.3%) patients.

Table 1

Patient and treatment characteristics in the overall study sample and according to the presence or absence of anterior cerebral artery embolism

Incidence and predictors of ACAE

ACAE occurred in 65 patients, giving an incidence rate of 9.4% (95% CI 7.2% to 11.6%). ACAE location was the A2 segment in 16 patients, the A3 segment in 18 patients, the callosomarginal artery in 18 patients, and distal branches in 13 patients. ACAE recanalization was attempted in 34 patients using aspiration (n=9) or SR (n=25). The procedure was technically successful in 24 patients and uneventful in all instances.

As shown in table 1, there was no significant difference between patients with and without ACAE regarding demographics and medical history, except for a lower rate of hypertension in patients with ACAE (43.1% vs 59.0%, P=0.013). The incidence of ACAE differed significantly in terms of location of the intracranial occlusion, with a higher incidence rate in tandem (19.3%) and ICA (15.3%) occlusions compared with isolated intracranial MCA occlusions (4.9%). ASPECTS <7 and non-cardioembolic etiology were significantly more frequent in patients with ACAE. Regarding treatment characteristics, use of IV thrombolysis prior to MT was not significantly associated with ACAE, contrary to the MT approaches. The lowest incidence rate of ACAE was found in patients treated with a distal aspiration catheter alone (5.7%), and the highest was found in patients treated with SR alone (14.2%). In addition, ACAE was significantly associated with a higher number of MT passes, but the procedure time was not significantly increased. There was no significant association with the use of balloon guide catheters or with adjuvant angioplasties. In multivariate analysis (see online supplementary table e–1), ICA occlusion (tandem or terminal), ASPECTS <7, increasing number of passes, and the use of SR alone were found to be independent predictors of ACAE.

Supplementary file 1

ACAE and outcomes

Figure 1 shows the distributions of reperfusion grade at the end of procedure and the 90 day clinical outcome according to the study group. Overall, a favorable outcome was achieved in 46.0% (95% CI 42.2% to 49.8%) of patients. Secondary outcomes rates were 83.2% (95% CI 80.4% to 86.0%) for successful reperfusion, 21.1% (95% CI 18.0% to 24.2%) for 90 day all cause mortality, 39.5% (95% CI 35.6% to 43.3%) for hemorrhagic complications, and 6.5% (95% CI 4.5% to 8.4%) for sICH.

Figure 1

(A) Distribution of post-treatment modified Treatment in Cerebral Infarction (mTICI) and (B) 90 day modified Rankin Scale (mRS) scores, according to the presence or absence of anterior cerebral artery embolism (ACAE). P values for comparison between the two study groups <0.0001 (Mann–Whitney U test).

As shown in table 2, a favorable outcome was significantly lower in patients with ACAE compared with those without (25.4% vs 48.2%; OR 0.37; 95% CI 0.20 to 0.66). After adjustment for independent ACAE predictors, this difference remained significant (adjusted OR 0.48; 95% CI 0.27 to 0.92). Similar findings were found after handling missing 90 day mRS values by multiple imputation (see supplementary table e–2). Regarding secondary outcomes, the rates of successful and complete reperfusion, excellent outcome, and early neurological improvement were higher in patients without ACAE compared with patients with ACAE, whereas the 90 day mortality and hemorrhagic complications rates were lower. Except for excellent outcome and sICH, all between group differences in favor of patients without ACAE remained significant after adjustment for independent predictors of ACAE (see supplementary table e–2).

Table 2

Outcomes according to the presence or absence of anterior cerebral artery embolism

ACAE and impact of reperfusion

When the analyses comparing clinical outcomes were stratified according to successful reperfusion status at the end of the procedure, we found no significant heterogeneity in the effect size of ACAE except for early neurological improvement (figure 2). The effect of successful reperfusion on favorable and excellent outcome was significantly greater in patients without ACAE (62.4% vs 23.6%; OR 3.57; 95% CI 2.12 to 5.99, P<0.001 for favorable outcome) whereas this benefit was not significant in patients with ACAE (30% vs 17.4%; OR 2.04; 95% CI 0.57 to 7.27, P=0.27).

Figure 2

Impact of anterior cerebral artery embolism (ACAE) on clinical outcomes according to successful reperfusion at the end of the procedure. A favorable outcome was defined as a 90 day modified Rankin Scale (mRS) score of 0 to 2 or equal to pre-stroke mRS score, and excellent outcome as a 90 day mRS of 0 to 1 or equal to pre-stroke mRS score. Early neurological improvement was defined as a National Institutes of Health Stroke Scale (NIHSS) score of 0–1 at 24 hours or a decrease of 4 or more points in the NIHSS score at 24 hours. ICH, intracerebral  hemorrhage.


The present study shows that a new embolism in the ACA territory during endovascular treatment of acute ischemic stroke is not uncommon, occurring in nearly 10% of patients, and is associated with worsened outcomes. In fact, ACAE patients experienced a twofold decrease in favorable outcome, whereas hemorrhagic complications and mortality rates were doubled. ACAE affects the prognosis and the successful reperfusion rates of MCA and tandem occlusions. The ACAE prognostic significance on survival outcomes was also confirmed in patients with successful reperfusion at the end of the procedure. Our results suggest that ACAE occurrence during the procedure may involve downstream clot fragment migration and may downplay the clinical benefit of successful reperfusion.

Incidence, risks factors, and related outcomes of new territory emboli have not been extensively studied. The initial reports of ACAE in AIS patients23 suggested a critical role of MT compared with IV or IA therapy, with a negative impact on outcome in the setting of ICA terminal occlusions. This might explain why at this time, studies that used thrombus fragmentation or grasping techniques and others now-obsolete devices, failed to demonstrate the benefit of acute ischemic stroke endovascular management compared with IV tissue plasminogen activator alone. The underestimated impact of new territory embolism with first generation thrombectomy devices could have contributed to the absence of MT benefit in the earlier studies. In a detailed analysis of the Interventional Management of Stroke III (IMS III) trial,24 using mostly first generation MT devices (Solitaire FR in only 4/200 ICA and M1 occlusions), emboli into new territories (ENT), usually ACA branches, occurred in 12.6% (for M1 occlusions) and resulted in a 13% difference in mRS 0–2 outcomes between subjects with and without new emboli. The rate of ENT increased to 22% for patients with ICA occlusions. With the advent of SR, the ACAE rate decreased to 11.4% in patients with M1 occlusions,17 but still with a considerable impact on outcome (3/14 (21%) (patients deteriorated clinically by 4 points on the NIHSS).

Among the first randomized MT controlled trials, Extending the Time for Thrombolysis in Emergency Neurological Deficits-Intra-Arterial (EXTEND-IA)5 reported 2 ENT (5.7%) and Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours (REVASCAT)4 5 cases of ENT (4.9%), but no detail regarding the outcome of these patients was available. In the Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) trial,1 an ENT rate of 8.6% was published. Thirteen symptomatic cases (5.6%) of ischemic stroke in a different vascular territory were documented. Once more, the outcome of these patients was not described. Recently, Endovascular Treatment for Small Core and Proximal Occlusion Ischemic Stroke (ESCAPE) trial investigators published their review of ischemia in new territories during MT.25 Eight infarcts in new territories after endovascular therapy (5%) were identified, with a significant reduction in clinical outcome (OR 0.25). The main limit of the classification was the significant differences in reported rates depending on whether CT or MR was used. ACA infarcts are described as less frequent than ACAE, and efficient rescue maneuvers of ACAE are considered to improve the global successful reperfusion at the end of the procedure.15 However, our results do not support the latter point and suggest that ACAE occurrence is far from inconsequential in the long term. ACAE may, at least in part, contribute to the disparity between angiographic success and clinical failure.

In our study period, we observed 65 ACAE, a number higher than ENT rates reported in recent publications.11 12 15 26 Our findings led us to question whether ENT identification is systematic among studies.

We have seen that among the factors associated with ACAE, the technique is important. In addition, it is a controllable factor. The development of MT techniques allowed a decrease in the emboli rate. Distal access/aspiration catheter in association with SR are currently used in practice, with a rate of new territory embolism of 5% compared with 11% with previous techniques.17 27 The technique using balloon guided catheters in association with SR has also been described to reduce ENT rates.28–30 In our study, the low rate of balloon guided catheter use (mainly due to the size incompatibility between balloon guided catheters and our main chosen technique) was certainly a limit, which may override the association between ACA emboli and SR use.

The ADAPT techniques show some interesting results, with a rate of periprocedural emboli in a new territory of 0–6% in studies using the ADAPT technique.9 11 12 The ADAPT approach may present with a lower risk of embolic complications due to the aspiration component allowing an en bloc clot extraction in up to 78%12 without passage through the thrombus, theoretically reducing the risk of fragmentation. Nevertheless, our results support the fact that SR alone without aspiration is an independent factor for ACAE, with a 2.6-fold increased risk.

Our data confirmed that occlusion location is an independent risk factor for ACAE.23 Tandem and ICA locations had a higher rate of ACAE with, respectively, 19.3%, 15.3% compared with 4.8% for MCA location. The pejorative impact of ACAE is constant, and the rate of favorable outcome at 3 months has been halved in patients with ICA and tandem occlusions, and reduced to a third in MCA occlusions. Additional ACAE predictors include large brain infarcts with ASPECT <7. With a lower ASPECT, flow deregulation from the suffering territory could spread microemboli into less resisting collateral branches.

Interestingly, ACAE was found to occur with the same frequency in patients receiving IV tissue plasminogen as in those not eligible for IV tissue plasminogen activator (9.5% vs 9.3%), in agreement with previous studies.18 26

The number of passes was an independent risk factor for ACAE. Despite the fact that the majority of ACAE occurred after the first pass of the MT maneuver, there was a link between ACAE and unsuccessful reperfusion of the prior occlusion, requiring multiple passes. Indeed, patients with ACAE have a lower rate of global reperfusion mTICI 2b/3 than the those without, even after adjustment for predictors such as initial location and device.

Even when successful reperfusion was achieved, patients with ACAE presented a lower rate of favorable outcome and higher rates of 90 day mortality and hemorrhagic complications. Furthermore, the effect of successful reperfusion on favorable and excellent outcome failed to reach statistical significance in patients with ACAE compare with those without. This discrepancy of favorable clinical outcome after successful reperfusion between patients with or without ACAE may be due to collateral impairment consecutive to microthrombi emboli.

Limitations of this study include the exclusion of patients with prior ACA occlusions and functional terminal ICA occlusions based on angio-MR (or angio-CT) and/or prior 3-axes DSA. Although our studied population was restrictive, it offered the opportunity to study a homogeneous population. We did not study the role of baseline collaterals on ACAE occurrence, which is certainly a limitation. A burden score evaluation is warranted. In fact, we used a qualitative approach, which did not integrate the impact of the thrombus load. In addition the absence of benefit of ACAE reperfusion was potentially affected by the small number of patients included in the study. Randomized evidence is needed to address this issue.

In our study, we showed that new embolism in ACA territories during endovascular treatment of acute ischemic stroke increases disability and mortality, even when successful reperfusion is reached. These findings support a critical impact of ACAE on prognosis and the need for strategies reducing clot fragmentation.


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  • Contributors VC: study concept and design, acquisition of the data, and interpretation of the data. RB, MP, and MM: study concept and design, acquisition of the data, interpretation of the data, study supervision, and critical revision of manuscript for intellectual content. HR, GC, SS, J-PD, DB, SE, WB, BM, and MO: acquisition of the data. JL: statistical analysis, interpretation of the data, and study supervision.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.

  • Competing interests RB and MP received institutional grants from Stryker, Medtronic, Microvention, and Balt. They are proctors for Medtronic Pipeline Cases. MM has been a consultant for Servier, Acticor, Boerhinger, and Medtroni.

  • Patient consent Not required.

  • Ethics approval The study was approved by the local ethics committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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