Aspiration thrombectomy as the first-line treatment of M2 occlusions

Abstract

Purpose

The aim of the present study was (i) to evaluate the safety and efficacy of aspiration thrombectomy in patients with M2 occlusions and (ii) to compare outcome of treatment of occlusion of different M2 segments.

Materials and methods

Between March 2016 and June 2019, 82 patients with acute ischemic stroke and isolated M2 occlusions were treated in cerebrovascular stroke center with aspiration thrombectomy as the first-line treatment. Functional outcomes of patients with different types of M2 occlusions were statistically compared. Multivariable logistic regression analysis was performed to determine the factors associated with good clinical outcome.

Results

The mean age was 71.9 ± 13.4 years, 47.6% were men. Aspiration thrombectomy alone was utilized in 72.5% of patients, with 27.5% of patients being treated with a combination of aspiration thrombectomy and stent retriever. At the three-month follow-up, there was no statistically significant difference in functional outcome between different types of M2 occlusions (p = 0.662), however in the underpowered analysis because of the small sample size of patients, with good clinical outcome mRS 0–2 in 50% of all treated patients. Symptomatic intracranial hemorrhage was found in 6.1% of patients. Lower age (OR 0.932, 95% CI 0.878–0.988) and lower NIHSS score upon admission (OR 0.893, 95% CI 0.805–0.991) were independent predictors of good clinical outcome.

Conclusion

Aspiration thrombectomy appeared to be a safe and effective first-line treatment option for patients with M2 occlusion, being the first-line option for almost three-quarters of patients.

Introduction

Endovascular treatment (EVT) has become the golden standard for the treatment of patients with acute ischemic stroke and large vessel occlusion of the M1 middle cerebral artery (MCA) and/or the internal carotid artery (ICA). In distal occlusions, endovascular procedures can be more challenging and are associated with a higher risk of periprocedural complications as a result of a smaller vessel diameter and a longer path to the occlusion.¹ Intravenous thrombolysis administration has been shown to be associated with a higher increase in the percentage of recanalization for distal occlusions in comparison with proximal occlusions.^2,3 In spite of the fact favorable results have been obtained in several studies, the optimal management of patients with M2 occlusion remains a matter of debate. The 2018 AHA/ASA guidelines recommend that in properly selected patients with M2 occlusion within 6 h after symptom onset, EVT with the use of stent retrievers can be performed; however, the benefits remain unclear (IIb recommendations).⁴ The aim of the present study was to analyze the safety and efficacy of EVT of M2 occlusions with aspiration thrombectomy as the first-line treatment and compare outcomes of patients with occlusion of different M2 segments.

Materials and methods

A single-center, retrospective analysis of patients who underwent EVT for M2 occlusions in our cerebrovascular stroke center between March 2016 and June 2019 was performed. The following clinical criteria upon admission were used for inclusion of patients for endovascular therapy: baseline National Institutes of Health Stroke Scale score (NIHSS) ≥6 or in patients with NIHSS < 6 and clinically relevant neurological deficit in eloquent area (aphasia, hemianopsia, etc.). Only patients with isolated M2 occlusion were included. Patients with tandem ICA and M2 occlusion, patients with combined M1/M2 occlusion were not included. Several MCA branching patterns have been described in the literature.^1,5–8 We divided M2 according to anatomical definition of MCA segments.¹ M2 branches were branches distal to the distal end of horizontal part of M1 segment. M2 branch was considered dominant if the diameter was larger or if the perfusion was greater than 50% of the MCA territory. If M2 branches were symmetric or supplying both 50% of MCA territory, they were considered codominant. Classification of M2 branches into segments was performed according to computed tomography (CT) angiography and digital subtraction angiography by two neurointerventionalists.

All patients underwent nonenhanced CT and CT angiography of extracranial and intracranial vasculature before procedure. In a selected group of patients (patients with unknown symptom onset, wake-up stroke, or stroke onset 6–24 h before EVT), perfusion CT was performed. If eligible for bridging intravenous thrombolysis, patients received IVT and were then treated with EVT.

EVT was performed under local anesthesia or conscious sedation. In all patients, the transfemoral approach was followed with a guiding catheter (NeuronMax 088, Penumbra), which was advanced into the ICA. The site of occlusion was reached with an aspiration catheter (4 MAX, ACE 60, or ACE 64, Penumbra), and aspiration thrombectomy was performed utilizing the ADAPT technique. If aspiration thrombectomy alone failed after two attempts to retrieve the clot, a combination of aspiration thrombectomy with stent retriever thrombectomy (Preset, Trevo, or Solitaire) was utilized. At 24 h after the procedure, control nonenhanced CT or magnetic resonance imaging (MRI) was performed.

Patients’ data, i.e. sex, age, comorbidities, and NIHSS score upon admission and after seven days after procedure, were collected. The ASPECTS score upon admission was evaluated by nonenhanced CT with automated software for ASPECTS score evaluation (eASPECTS) (Brainomix). Several procedural and technical characteristics were evaluated, including intravenous thrombolysis administration, time from symptom onset to start of EVT, time from puncture to recanalization, and recanalization success, which was defined as a Thrombolysis In Cerebral Infarction (TICI) score of 2b/3. Hemorrhagic complications were evaluated by control nonenhanced CT according to the ECASS III criteria.⁹ Functional outcome was evaluated at seven days and at three months after EVT by the modified Rankin scale (mRs). Good clinical outcome was defined as mRs 0–2, bad clinical outcome as mRS 3–6.

Statistical analysis

Results were evaluated statistically with Graph Pad Prism statistical software, version 8.3 (San Diego, CA, USA) and SPSS 26.0 statistical package (IBM SPSS, Chicago, IL, USA). The Shapiro-Wilk test was used to verify the normal distribution of the analyzed data. Unpaired t-test in case of parametric (onset-to-groin time and NIHSS score upon admission) and independent-sample Mann-Whitney U test in case of non-parametric continuous variables were used to analyse the differences between two patient groups. The differences between categorical variables were analysed by Fisher’s exact test. Pearson’s χ² test was used to analyse the differences between functional outcome after endovascular treatment and the site of occlusion of different M2 segments. Multifactorial ordinal logistic regression with proportional odds was run to determine the effect of independent factors for association with good outcome of patients. p-Values less or equal to 0.05 were considered to indicate significant differences.

Results

Basic demographic, clinical, and imaging data are summarized in Table 1. A total of 82 consecutive patients with M2 occlusion who underwent EVT fulfilled the study criteria. The different types of M2 occlusion were distributed as follows: dominant M2 branch 51%, codominant M2 branch 44%, and nondominant branch 5%, left side was occluded in 58.5%, right side in 41.5% of patients. In the whole study group, the mean age was 71.9 ± 13.4 years, 47.6% were men, and the median NIHSS score upon admission was 11.11 ± 5.14. The mean ASPECTS score upon admission, as determined by nonenhanced CT, was 9.22 ± 1.24; 50% of patients received intravenous thrombolysis before EVT. The mean time from symptom onset to start of EVT was 262.76 ± 109.35 min, and the mean time from puncture to recanalization was 27.22 ± 15.81 min. The mean number of passes during one EVT was 2.06 ± 1.18. Successful recanalization (a TICI score of 2b/3) was achieved in 91.5% of the patients. Aspiration thrombectomy alone was sufficient in 72.5% of patients, and in the remaining 27.5% of patients, a combination of aspiration thrombectomy with stent retriever thrombectomy was utilized. Symptomatic intracranial hemorrhage was found in 6.1% of patients. No other complications regarding the endovascular procedure were found. No statistical difference was found in NIHSS score upon admission between different M2 segments occlusion groups (p = 0.523) (Figure 1). In 80.49% of patients, the NIHSS score had decreased seven days after EVT (from 11.11 ± 5.14 to 6.32 ± 8.12) (p < 0.001) (Figure 2). At the three-month follow-up, no statistically significant difference in good and bad outcome was observed between patients with dominant, codominant, or nondominant M2 occlusion (p = 0.662), with good clinical outcome mRS 0–2 in 50% of all study patients after endovascular treatment of M2 occlusion. Patients with bad clinical outcome mRS 3–6 had significantly higher age (p < 0.001), more sICH after thrombectomy (p =  0.05), higher NIHSS upon admission (p < 0.001), more often diabetes mellitus (p = 0.022), and also hypertension (p = 0.013) (Table 1). However, in multivariable ordinal logistic regression analysis, lower age (OR 0.932, 95% CI 0.878–0.988) and lower NIHSS score upon admission (OR 0.893, 95% CI 0.805–0.991) were independent predictors of good clinical outcome at three months’ follow-up (Table 2).

Table 1.

Demographic, clinical, and procedural data of patients.

	All patients	Good outcome (mRs 0–2)	Bad outcome (mRS 3-6)	Statistical differencea
Number of patients	82	41	41
Age	71.9 ± 13.4	66.8 ± 15.7	77 ± 8.2	<0.001
Male	47.6%	53.7%	41.5%	0.377
Hypertension	84.1%	73.2%	95.1%	0.013
CAD	48.8%	43.9%	53.7%	0.508
Atrial fibrillation	45.1%	41.5%	48.8%	0.657
Diabetes mellitus	37.8%	24.4%	51.2%	0.022
Dyslipoproteinemia	59.8%	53.7%	65.9%	0.368
Pre-event mRs	0.22 ± 0.7	0.15 ± 0.57	0.29 ± 0.81	0.293
Administration of iv tPA	50%	46.3%	53.7%	0.659
Onset-to-groin time (min)	262.76 ± 109.35	282.97 ± 120.72	245.84 ± 97.29	0.165
Groin-to-recanalization time (min)	27.22 ± 15.81	25.76 ± 12.63	28.68 ± 18.5	0.749
Number of passes (mean ± SD)	2.06 ± 1.18	2 ± 1.12	2.12 ± 1.25	0.747
ASPECTS score upon admission	9.22 ± 1.24	9.2 ± 1.21	9.24 ± 1.28	0.711
TICI score of 2b/3 after EVT	91.5%	92.7%	90.2%	1.000
NIHSS score upon admission	11.11 ± 5.14	9.63 ± 4.47	12.59 ± 5.38	0.008
NIHSS score at day 7	6.32 ± 8.12	2.85 ± 3.17	9.88 ± 9.96	<0.001
mRs at day 7	2.46 ± 1.85	1.37 ± 1.22	3.56 ± 1.72	<0.001
mRs at three months	2.76 ± 2.39	0.68 ± 0.79	4.83 ± 1.47	<0.001
sICH	6.1%	0%	12.2%	0.05
M2 segments occlusion
Dominant	51.2%	56.1%	46.3%	0.662
Codominant	43.9%	39%	48.8%
Nondominant	4.9%	4.9%	4.9%
Side of M2 occlusion
Right	41.5%	36.6%	46.3%	0.502
Left	58.5%	63.4%	53.7%

sICH: symptomatic intracranial hemorrhage; NIHSS: National Institute of Health Scale System; mRs: modified Rankin scale; CAD: coronary artery disease; TICI: Thrombolysis In Cerebral Infarct score; iv tPA: intravenous tissue plasminogen activator; SD: standard deviation.

^aStatistical test used is described in Methods section.

Figure 1.

NIHSS before thrombectomy in different M2 segments.

Figure 2.

The relationship between NIHSS before thrombectomy and NIHSS 7 days after thrombectomy.

NIHSS: National Institutes of Health Stroke Scale score.

Table 2.

Results of the multivariable ordinal logistic regression analysis (proportional odds model) for association with good outcome (mRs 0–2) of patients.

	Wald χ2p	OR	OR 95% CI
Age	0.018	0.932	0.878–0.988
Hypertension	0.334	0.411	0.067–2.500
Diabetes mellitus	0.085	0.398	0.140–1.134
NIHSS score upon admission	0.033	0.893	0.805–0.991

NIHSS: National Institute of Health Scale System; OR: odds ratio; CI: confidence interval.

Discussion

Despite the fact that several papers have reported favorable results, prognosis and ideal management of patients with distal occlusions in the anterior circulation of the brain remain a matter of debate. Several studies have investigated the outcomes of patients treated for M2 occlusions. In the meta-analysis of M2 occlusions conducted by Chen et al., excellent and good outcomes at the three-month follow-up were observed in 40% and 62% of patients, respectively.¹⁰ In the meta-analysis of Saber et al., functional independence (mRs 0–2) was observed in 59% of patients.⁶ In the HERMES meta-analysis, 130 patients with M2 occlusion were analyzed, with modified TICI (mTICI) scores of 2b/3 in 59.2% of patients and better clinical outcome in patients treated with EVT compared with the control group (58.2% vs. 39.7% of patients, p = 0.03).¹¹ In our study, good functional outcome (mRs 0–2) after three months was achieved in 50% of patients treated for M2 occlusions.

Outcomes of patients with M2 and M1 occlusions have been compared in several studies. The meta-analysis of Saber et al. did not reveal a significant difference in recanalization (TICI score) and mortality between patients with M1 or M2 occlusions; despite the more symptomatic intracranial hemorrhages, functional outcome was better, probably due to lower NIHSS scores upon admission.⁶ Navia et al. found that good postprocedure reperfusion (an mTICI score of 2b/3) (93% vs. 92%, p = 1.00), functional independence (57% vs. 70%, p = 0.18), symptomatic intracranial hemorrhage (1.6% vs. 2.7%, p = 0.55), device- or procedure-related serious adverse events at 30 days (4.0% vs. 8.1%, p = 0.39), and mortality at 90 days (6.6% vs. 2.7%, p = 0.69) were comparable between patients with M1 and M2 occlusions.¹² In the present study, we did not compare results of endovascular treatments for M1 and M2 occlusions.

The question of how to treat patients with dominant or nondominant branch M2 occlusions remains unresolved. In the study of Compagne et al., no evidence was found that patients with either a dominant or a nondominant M2 occlusion should be routinely excluded from EVT.¹³ In a study of de Castro Afonso et al., 27 patients (90%) had a dominant M2 branch and all were occluded.¹³ In the HERMES meta-analysis, endovascular therapy was most effective in patients with proximal M2 segment MCA occlusions (n = 116, adjusted OR 2.68, 95% CI 1.13 to 6.37) and in patients with dominant M2 segment MCA occlusions (n = 73, adjusted OR 4.08, 95% CI 1.08 to 15.48).¹¹ The results of our study, likely because of the small sample size of patients with the underpowered analysis, showed no difference in clinical outcome between endovascular treatment of dominant, codominant, or nondominant M2 branch occlusions. These results together with our findings from similar NIHSS distribution between dominant, codominant, and nondominant occluded M2 branches before EVT support the theory, that patients with M2 branch occlusion should not be discouraged from endovascular therapy according to caliber of M2 branch.

The optimal EVT for clot retrieval remains a matter of debate. Most studies analyzing EVT in M2 occlusions were performed with mechanical thrombectomy with stent retriever. Data regarding aspiration thrombectomy are limited. Several studies have compared aspiration thrombectomy with stent retriever thrombectomy and obtained comparable results.^14–17,18 In a multicenter trial studying M2 occlusions, utilization of a newer-generation pump aspiration catheter resulted in outcomes similar to those obtained with a stent retriever, but worse outcomes were observed with the manual aspiration technique.¹⁶ In the Contact Aspiration vs. Stent Retriever for Successful Revascularization (ASTER) trial, in the subgroup analysis with M2 occlusions, authors found no statistically significant differences between stent retriever thrombectomy and aspiration thrombectomy, with a recanalization rate of 87.3%, an sICH rate of 5%, and a functional independence rate of 52.6% at the three-month follow-up.¹⁷ In the present study, we have only employed aspiration thrombectomy (with the ADAPT technique) in 72.5% of patients to retrieve the clot; in the remaining 27.5% of patients, after failure of aspiration alone, a combination of aspiration thrombectomy with stent retriever thrombectomy was utilized. Successful recanalization (a TICI score of 2b/3) was achieved in 91.5% of patients. The mean procedure time from puncture to recanalization in our study was 27 min, which is shorter than in other studies, where it ranged from 29 to 64 min.^1,13 We hypothesize this is because in the majority of cases, we only employed aspiration thrombectomy. These results are in concordance with the COMPASS study, which compared stent retriever thrombectomy and aspiration thrombectomy and found significantly shorter procedure times in the aspiration thrombectomy group (22 min) than in the stent retriever group (33 min).¹⁴

Post endovascular therapy symptomatic intracranial hemorrhage remains the major concern of M2 occlusion treatment. In the meta-analysis by Saber et al., the rate of post endovascular therapy symptomatic intracranial hemorrhage was 10%.⁶ In another meta-analysis, symptomatic intracranial hemorrhage was observed in 5% of patients.¹⁰ In our study, the rate of symptomatic intracranial hemorrhage was 6.1%.

Recanalization rates following IVT for distal occlusions have been reported to be higher than for proximal occlusions.³ However, the successful recanalization rate with only tissue plasminogen activator administration has been shown to be only 6%.¹⁹ In a study by Sarraj et al., the rate of good outcomes was higher for endovascular therapy (62.8%) than for medicinal management alone (35.4%).²⁰ In our study, 50% of patients received IVT before EVT, and none of those patients achieved complete recanalization (a TICI score of 2b/3) after IVT before EVT. However, we did not analyse patients who only received IVT for M2 occlusion treatment and did not undergo thrombectomy due to clinical improvement after IVT.

Limitations of the study

We wish to mention several limitations of the study: (i) the retrospective, single-center design, (ii) the lack of a control group, and (iii) the small sample size of patients in the M2 subgroups.

Conclusion

In conclusion, our results showed that aspiration thrombectomy appeared to be a safe and effective first-line treatment option for patients with M2 occlusion. In more than one-quarter of thrombectomies, a combination of aspiration thrombectomy and stent retriever thrombectomy had to be utilized. No difference in functional outcome between dominant, codominant, and nondominant M2 branch occlusion was observed; however given the small sample size of patients, these results will need to be verified on a larger sample size of patients.

Authors’ contribution

JH, JHG and AK designed the model of the study. MH, MM, PJ carried out the implementation and performed the statistical analysis. AK, JH, JHG wrote the article with input from all authors. AK and GK were in charge of overall direction and planning.

Declaration of conflicting interests

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

Ethical approval

Written informed patient consent for publication of this study has been obtained.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Andrej Klepanec https://orcid.org/0000-0002-7460-2974