Clinical outcomes of endovascular treatment in patients with M2 segment occlusion of the middle cerebral artery of different etiologies: A retrospective study

doi:10.21203/rs.3.rs-4808066/v1

Download PDF

Research Article

Clinical outcomes of endovascular treatment in patients with M2 segment occlusion of the middle cerebral artery of different etiologies: A retrospective study

https://doi.org/10.21203/rs.3.rs-4808066/v1

This work is licensed under a CC BY 4.0 License

You are reading this latest preprint version

Background

Distal medium vessel occlusion may lead to severe neurological deficits. The aim of this study was to investigate the differences in endovascular treatment (EVT) procedure and their impact on clinical outcomes in patients with different etiologies of the M2 segment of the middle cerebral artery (M2-MCA) occlusion.

Methods

We conducted a retrospective analysis of patients with M2-MCA occlusion treated with endovascular treatment at Army Medical Center from January 2015 to July 2023. Patients were divided into atherosclerosis group and embolization group, and we determined the etiology of stroke based on the imaging features during EVT. Procedure-related outcomes included recanalization rates, treatment modalities, and procedural complications. Clinical outcomes included the good outcome (modified Rankin Scale score 0–2) at 90 days, incidence of symptomatic intracranial hemorrhage (sICH) and any intracranial hemorrhage within 24 hours, and mortality at 90 days.

Results

A total of 81 patients were included in the analysis, and the numbers of patients in the atherosclerosis and embolization groups were 20 and 61, respectively. Patients in the embolization group treated with more number of mechanical thrombectomy (2 [1–3] vs 1 [1–2], P = 0.028). However, the total number of EVT (2.5 [1–4] vs 2 [1–3], P = 0.036) and the proportion of patients treated with rescue therapy (50.0% vs 1.6%, P<0.001) were significantly greater in the atherosclerosis group. The recanalization rate and incidence of procedural complications were not significantly different between the two groups. The good outcome at 90 days, incidence of sICH and any intracranial hemorrhage within 24 hours, and mortality at 90 days were also no statistical difference between the two groups.

Conclusion

For patients with M2-MCA occlusion of different etiologies, neurointerventionalists may choose different EVT modalities. There were no significant differences in recanalization rates, procedural complications, or clinical outcomes.

distal medium vessel occlusion

ischemic stroke

mechanical thrombectomy

endovascular treatment

atherosclerosis

embolization

Approximately 25–40% of patients with acute ischemic stroke (AIS) are the result of distal medium vessel occlusions (DMVOs)[1]. In these patients, the volume of infarction is smaller than that of large vessel occlusions (LVOs), but it may still lead to severe disability. Among these, patients with M2 segment of the middle cerebral artery (M2-MCA) occlusion generally have the most severe symptoms, with six-month functional dependency in 60% and mortality in 24%[2]. Current guidelines recommend intravenous thrombolysis for DMVOs rather than endovascular treatment (EVT)[3]. However, about 50% of DMVOs patients fail to reperfusion after intravenous thrombolysis[4, 5].

In recent years, the role of EVT in DMVOs has been increasingly emphasized by neurointerventionalists as smaller-sized stents and catheters have become available[6–8]. However, the mechanical thrombectomy (MT) path of DMVOs is longer and more tortuous, and the risk of various complications such as hemorrhage transformation, vasospasm, and arterial dissection may be increased[1, 9]. Hence, while improving the efficacy, safety is also a concern in EVT for DMVOs. How to choose a more reasonable EVT modality has become a very important issue.

In this study, we retrospectively analyzed patients with M2-MCA occlusion who were treated with EVT. To observe the differences in procedure modalities of patients with different stroke etiologies and their effects on clinical outcomes.

Study population

Retrospective analysis of AIS patients who were treated with EVT at Army Medical Center from January 2015 to July 2023. We included patients aged 18 years or older with a diagnosis of M2-MCA occlusion (which can be combined with distal vessel occlusion) confirmed by computed tomography (CT) angiography or digital subtraction angiography within 24 hours of symptom onset. Exclusion criteria included pre-stroke modified Rankin scale (mRS) score of 2–5, combined with internal carotid artery or M1-MCA occlusion, M2-MCA occlusion resulting from EVT of the M1-MCA, cerebral angiography or intra-arterial thrombolysis only, and loss to follow-up at 90 days.

Patient stratification

Stroke etiology was divided by two experienced neurointerventionalists based on the imaging features during the procedure. Atherosclerosis group was defined as (1) “Microcatheter First-Pass effect" or “Stent-unsheathed effect” could be observed[10, 11], (2) residual stenosis >70% at the occlusion site, (3) residual stenosis >50% with antegrade flow impairment or a reocclusion tendency after thrombectomy[12]. Embolization group was defined as no such “effect” was observed and no stenosis after recanalization.

All patients were treated with stent retriever, catheter aspiration or combination of both. If the occlusion vessel is not recanalized or antegrade flow cannot be maintained after MT, rescue therapy is needed. Rescue therapy includes balloon angioplasty and stenting, both of which only count toward the total number of EVT and not toward the number of MT.

Outcome measures and follow-up

Procedure-related outcomes included successful recanalization (modified Thrombolysis In Cerebral Infarction [mTICI] score 2b-3), complete recanalization (mTICI score 3), one-pass recanalization, number of MT, total number of EVT, rescue therapy, vessel rupture, distal embolization, vasospasm, and arterial dissection. Clinical outcomes included the good outcome (modified Rankin Scale score 0–2) at 90 days, symptomatic intracranial hemorrhage (sICH) and any intracranial hemorrhage within 24 hours, and mortality at 90 days.

Dual-energy CT of the head was examined at the end of EVT and 24 ± 6 hours after EVT, and was compared with preoperative head CT. Intracranial hemorrhage was considered to have occurred if a hyperdense area presented on the follow-up CT. sICH was defined as intracranial hemorrhage with an increase of 4 or more points on the National Institutes of Health Stroke Scale (NIHSS)[13]. Patients were followed up by trained medical staff at 90 days after stroke, either by telephone or in an outpatient clinic.

Statistical methods

Continuous variables were expressed as median and interquartile spacing (IQR) or mean and standard deviation (SD) and were analyzed via the Student's t-test or the Mann-Whitney U test. Categorical variables were expressed as frequency (percentage), and analyzed via the χ² test or the Fisher's exact test. Binary logistic regression was used to analyze clinical factors that may affect patient outcomes. Statistics were considered significant for P-values < 0.05. IBM SPSS Statistics 24.0 was used for all statistical analyses.

Patient population

A total of 81 patients were included, 20 (24.7%) in the atherosclerosis group and 61 (75.3%) in the embolization group. Patients in the atherosclerosis group had a greater prevalence of hypertension (80.0% vs 50.8%, P = 0.022) and diabetes (45.0% vs 18.0%, P = 0.033). Atrial fibrillation was more common in the embolization group (10.0% vs 68.9%, P < 0.001). Other baseline characteristics were not significantly different between the two groups (Table 1).

Table 1

Baseline demographics of patients with different etiologies
	Total (n = 81)	Atherosclerotsis group (n = 20)	Embolization group (n = 61)	P value
Age, years	70 (59.5–78)	67.5 (54–77)	72 (63.5–78.5)	0.357
Male	38 (46.9%)	12 (60.0)	26 (42.6)	0.177
left hemisphere	38 (46.9)	11 (55.0)	27 (44.3)	0.404
Thrombolysis	28 (34.6)	7 (26.9)	21 (34.4)	0.493
Hypertension	47 (58.0)	16 (80.0)	31 (50.8)	0.022
Diabetes mellitus	20 (24.7)	9 (45.0)	11 (18.0)	0.033
Atrial fibrillation	44 (54.3)	2 (10.0)	42 (68.9)	<0.001
Admission NIHSS	14.22 ± 6.70	12.30 ± 5.45	14.85 ± 6.98	0.140
ASPECETS	8 (7–10)	8 (7–10)	8 (7–10)	0.630

ASPECTS indicates Alberta Stroke Program Early Computed Tomography Score; NIHSS, National Institutes of Health Stroke Scale.

Procedure-related outcomes

Patients in the embolization group were treated with more number of MT [2 (1–3) vs 1 (1–2), P = 0.028], but the total number of EVT [2.5 (1–4) vs 2 (1–3), P = 0.036] and the proportion of patients treated with rescue therapy (50.0% vs 1.6%, P < 0.001) were significantly greater in the atherosclerosis group. Successful recanalization, complete recanalization, one-pass recanalization, and other procedural complications did not differ statistically between the two groups. However, there was a trend toward a higher one-pass recanalization rate in the embolization group (45.9% vs 25.0%, P = 0.099, Table 2).

Table 2

Procedure-related outcomes in patients with different etiologies
	Total (n = 81)	Atherosclerotsis group (n = 20)	Embolization group (n = 61)	P value
mTICI 2b-3	73 (90.1%)	19 (90.0%)	55 (90.2%)	0.983
mTICI 3	39 (48.1%)	10 (50.0%)	29 (47.5)%	0.849
one-pass recanalization	33 (40.7%)	5 (25.0%)	28 (45.9%)	0.099
number of thrombectomy	2 (1–3)	1 (1–2)	2 (1–3)	0.028
total number of EVT	2 (1–3)	2.5 (1–4)	2 (1–3)	0.036
rescue therapy	11 (13.6%)	10 (50.0%)	1 (1.6%)	<0.001
vessel rupture	3 (3.7%)	1 (5.0%)	2 (3.3%)	1.000
distal embolization	12 (14.8%)	3 (15.0%)	9 (14.8%)	1.000
vasospasm	3 (3.7%)	0 (0.0%)	3 (4.9%)	0.571
arterial dissection	1 (1.2%)	1 (5.0%)	0 (0.0%)	0.247

EVT indicates endovascular treatment; mTICI, modified thrombolysis in cerebral infarction.

Clinical outcomes

Good outcome was achieved in 55.0% of patients in the atherosclerosis group, and 59.0% of patients in the embolization group. The difference between the two groups was not statistically significant (Table 3, Fig. 1). After adjusting for other factors, stroke etiology still had no significant effect on good outcome at 90 days. However, as the admission NIHSS score increased, the likelihood of good outcome decreased (adjusted OR 0.826, 98% CI 0.743–0.919, P < 0.001, Table 4). A total of 3 patients had sICH, 1 in the atherosclerosis group and 2 in the embolization group, with no statistically difference between the two groups. The incidence of intracranial hemorrhage within 24 hours and mortality at 90 days were also not significantly different between the two groups (Table 3).

Table 3

Clinical outcomes in patients with different etiologies
	Total (n = 81)	Atherosclerosis group (n = 20)	Embolization group (n = 61)	P value
mRS ≤ 2	47 (58.0%)	11 (55.0%)	36 (59.0%)	0.752
sICH	3 (3.7%)	1 (5.0%)	2 (3.3%)	1.000
Intracranial hemorrhage	23 (28.4%)	5 (25.0%)	18 (29.5%)	0.698
Mortality	11 (13.6%)	4 (20.0%)	7 (11.5%)	0.555

mRS indicates modified Rankin Scale; sICH, symptomatic intracranial hemorrhage.

Table 4

Binary logistic regression model for good outcome at 90 days (mRS ≤ 2)
Variables	aOR(95% CI)	P value
Age	0.980(0.938–1.023)	0.351
Sex (female vs male)	1.570(0.447–5.518)	0.482
Etiologies (embolization vs atherosclerosis )	2.485(0.677–9.121)	0.170
Thrombolysis	0.733(0.200-2.691)	0.640
Admission NIHSS	0.826(0.743–0.919)	<0.001
ASPECETS	1.307(0.955–1.790)	0.095

ASPECTS indicates Alberta Stroke Program Early Computed Tomography Score; aOR, adjusted odds ratio; CI, confidence interval; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale.

The results of this study showed that a greater proportion of patients with M2-MCA occlusion treated with EVT were embolization type. This may be due to the fact that the intracranial collateral circulation is worse in patients with embolization than in those with atherosclerosis, and the NIHSS score may be higher, which ultimately leads to more patients with embolization treated with EVT. Further analysis revealed that neurointerventionalists were more likely to perform MT in patients whose etiology was determined to be embolization. In contrast, in atherosclerotic patients, neurointerventionalists were more aggressive in choosing rescue therapy such as balloon angioplasty or stenting if MT was ineffective. Although the modality of EVT varies among patients with different etiologies, there are no significant differences in recanalization rate, procedural complications, or clinical outcomes.

Currently, EVT is one of the standard treatment options for restoring cerebral perfusion in AIS-LVO, and EVT can significantly improve the outcomes of such patients[3, 14–16]. Because the occlusion of large vessel branches in important locations can also lead to severe disability, it is reasonable to expand the target population of EVT to selected DMVOs. A pooled analysis of 130 patients with MCA-M2 occlusions showed that EVT was associated with favorable outcome compared with medical therapy alone. The greatest benefit was observed in proximal and dominant MCA-M2 occlusions[17]. The patients enrolled in this study also had MCA-M2 occlusion and an averageNIHSS score of 14 at admission, indicating definite neurologic deficits. EVT in such patients is essential and the therapeutic benefit will be more pronounced.

A meta-analysis of previous studies showed that the overall recanalization rate of DMVOs was 77.0%, the one-pass recanalization was 51.0%, the proportion of good outcome was 51.3%, the incidence of sICH was 5.7%, and the mortality was 19.1%[18]. The results of our study were noninferior, or even superior, to these outcomes. We considered that the likely reason for this is that neurointerventionalists choose a more reasonable EVT modality for different etiologies. Especially in atherosclerotic patients, neurointerventionalists did not repeatly attempt MT, but performed rescue therapy as early as possible, so that the final successful recanalization could be as high as 90%, despite the low one-pass recanalization rate. In addition, reducing the number of unnecessary MT mitigates endothelial injury and reduces the risk of hemorrhage transformation. Ultimately, these can lead to better long-term outcome and lower mortality.

In this study, the median number of MT in patients with embolization was 2, and the proportion of good outcome was generally consistent with the results of previous studies on DMVOs or LVOs[14, 18, 19]. Regarding the relationship between the number of MT and patient outcome, the results of studies in AIS-LVO have shown that less than 3 recanalization attempts is a reasonable choice, and that too many recanalization attempts increase the risk of intracranial hemorrhage and are significantly associated with poor outcome[20–22]. The results of this study suggest that recanalization after 1 or 2 MTs may also correlate with good outcome in patients with DMVOs. In the future, more studies should be conducted to analyze the relationship between the number of MT and clinical outcome in patients with DMVOs.

Limitation

First, this was a retrospective observational study, and some other undocumented causes may have affected patient outcome. Second, the devices used during EVT were not exactly the same in different patients, and different devices may lead to different recanalization efficiencies. Third, this study did not analyze the impact of each MCA-M2 branch occlusion on patient outcomes. In fact, different branch occlusions may present with clinical symptoms of varying severity. Fourth, this study grouped patients based on imaging during EVT, and it remains a challenge for neurologists to accurately determine stroke etiology before EVT.

AIS acute ischemic stroke

CT computed tomography

DMVO distal medium vessel occlusion

EVT endovascular treatment

LVO large vessel occlusion

M2-MCA M2 segment of the middle cerebral artery

mRS modified Rankin scale

MT mechanical thrombectomy

mTICI Thrombolysis In Cerebral Infarction

NIHSS National Institutes of Health Stroke Scale

sICH symptomatic intracranial hemorrhage

Ethics approval and consent to participate

This retrospective study conformed to the principles of the Declaration of Helsinki and was approved by the medical ethics committee of Army Medical Center of PLA. Since this study was retrospective, we waived patient informed consent.

Consent for publication

Not applicable

Data availability

The data of this study are available from the corresponding author upon reasonable request.

Competing interests

The authors declare no competing interests.

Funding

This work was supported by the National Natural Science Foundation of China (82071322) and National Natural Science Foundation of Chongqing, China (CSTB2022NSCQ-MSX1100).

Authors' contributions

Study concept and design: Meng Zhang, Wangsheng Jin and Yaning Xu. Drafting of the manuscript: Yaning Xu and Wangsheng Jin. Statistical analysis: Yaning Xu. Performing endovascular treatment and acquisition of data: Chengchun Liu, Qiuju Zhao and Wei Li. Responsible for the overall content as the guarantor: Meng Zhang.

Acknowledgements

The authors thank all the participants for their contribution to this study and thank the physicians for their efforts in the treatment process.

Saver JL, Chapot R, Agid R, Hassan A, Jadhav AP, Liebeskind DS, et al. Thrombectomy for Distal, Medium Vessel Occlusions: A Consensus Statement on Present Knowledge and Promising Directions. Stroke. 2020;51(9):2872-84.
Smith WS, Lev MH, English JD, Camargo EC, Chou M, Johnston SC, et al. Significance of large vessel intracranial occlusion causing acute ischemic stroke and TIA. Stroke. 2009;40(12):3834-40.
Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, et al. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019;50(12):e344-e418.
Seners P, Turc G, Maïer B, Mas JL, Oppenheim C, Baron JC. Incidence and Predictors of Early Recanalization After Intravenous Thrombolysis: A Systematic Review and Meta-Analysis. Stroke. 2016;47(9):2409-12.
Menon BK, Al-Ajlan FS, Najm M, Puig J, Castellanos M, Dowlatshahi D, et al. Association of Clinical, Imaging, and Thrombus Characteristics With Recanalization of Visible Intracranial Occlusion in Patients With Acute Ischemic Stroke. Jama. 2018;320(10):1017-26.
Kühn AL, Wakhloo AK, Lozano JD, Massari F, De Macedo Rodrigues K, Marosfoi MG, et al. Two-year single-center experience with the 'Baby Trevo' stent retriever for mechanical thrombectomy in acute ischemic stroke. Journal of neurointerventional surgery. 2017;9(6):541-6.
Altenbernd J, Kuhnt O, Hennigs S, Hilker R, Loehr C. Frontline ADAPT therapy to treat patients with symptomatic M2 and M3 occlusions in acute ischemic stroke: initial experience with the Penumbra ACE and 3MAX reperfusion system. Journal of neurointerventional surgery. 2018;10(5):434-9.
Dobrocky T, Bellwald S, Kurmann R, Piechowiak EI, Kaesmacher J, Mosimann PJ, et al. Stent Retriever Thrombectomy with Mindframe Capture LP in Isolated M2 Occlusions. Clinical neuroradiology. 2020;30(1):51-8.
Rai AT, Hogg JP, Cline B, Hobbs G. Cerebrovascular geometry in the anterior circulation: an analysis of diameter, length and the vessel taper. Journal of neurointerventional surgery. 2013;5(4):371-5.
Yi TY, Chen WH, Wu YM, Zhang MF, Zhan AL, Chen YH, et al. Microcatheter "First-Pass Effect" Predicts Acute Intracranial Artery Atherosclerotic Disease-Related Occlusion. Neurosurgery. 2019;84(6):1296-305.
Chen WH, Yi TY, Zhan AL, Wu YM, Lu YY, Li YM, et al. Stent-unsheathed effect predicts acute distal middle cerebral artery atherosclerotic disease-related occlusion. Journal of the neurological sciences. 2020;416:116957.
Lee JS, Hong JM, Lee KS, Suh HI, Demchuk AM, Hwang YH, et al. Endovascular Therapy of Cerebral Arterial Occlusions: Intracranial Atherosclerosis versus Embolism. J Stroke Cerebrovasc Dis. 2015;24(9):2074-80.
Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, et al. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). Jama. 1995;274(13):1017-25.
Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, et al. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet (London, England). 2016;387(10029):1723-31.
Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, et al. Thrombectomy for Stroke at 6 to 16 Hours with Selection by Perfusion Imaging. N Engl J Med. 2018;378(8):708-18.
Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, et al. Thrombectomy 6 to 24 Hours after Stroke with a Mismatch between Deficit and Infarct. N Engl J Med. 2018;378(1):11-21.
Menon BK, Hill MD, Davalos A, Roos Y, Campbell BCV, Dippel DWJ, et al. Efficacy of endovascular thrombectomy in patients with M2 segment middle cerebral artery occlusions: meta-analysis of data from the HERMES Collaboration. Journal of neurointerventional surgery. 2019;11(11):1065-9.
Bilgin C, Hardy N, Hutchison K, Pederson JM, Mebane A, Olaniran P, et al. First-line thrombectomy strategy for distal and medium vessel occlusions: a systematic review. Journal of neurointerventional surgery. 2023;15(6):539-46.
Majoie CB, Cavalcante F, Gralla J, Yang P, Kaesmacher J, Treurniet KM, et al. Value of intravenous thrombolysis in endovascular treatment for large-vessel anterior circulation stroke: individual participant data meta-analysis of six randomised trials. Lancet (London, England). 2023;402(10406):965-74.
Namitome S, Uchida K, Shindo S, Yoshimura S, Sakai N, Yamagami H, et al. Number of Passes of Endovascular Therapy for Stroke With a Large Ischemic Core: Secondary Analysis of RESCUE-Japan LIMIT. Stroke. 2023;54(8):1985-92.
Ringheanu VM, Tekle WG, Preston L, Sarraj A, Hassan AE. Higher number of stent-retriever thrombectomy passes significantly increases risk of mass effect, poor functional outcome, and mortality. Interventional neuroradiology : journal of peritherapeutic neuroradiology, surgical procedures and related neurosciences. 2023;29(6):674-82.
Winkelmeier L, Faizy TD, Broocks G, Meyer L, Heitkamp C, Brekenfeld C, et al. Association Between Recanalization Attempts and Functional Outcome After Thrombectomy for Large Ischemic Stroke. Stroke. 2023;54(9):2304-12.

No competing interests reported.

Download PDF

Editorial decision: Revision requested
26 Jul, 2024
Editor assigned by journal
26 Jul, 2024
Submission checks completed at journal
26 Jul, 2024
First submitted to journal
26 Jul, 2024

You are reading this latest preprint version

Clinical outcomes of endovascular treatment in patients with M2 segment occlusion of the middle cerebral artery of different etiologies: A retrospective study

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

Background

Methods

Study population

Patient stratification

Outcome measures and follow-up

Statistical methods

Results

Patient population

Procedure-related outcomes

Clinical outcomes

Discussion

Limitation

Conclusion

Abbreviations

Declarations

References

Additional Declarations

Status:

Version 1