Safety and Efficacy of Thrombectomy for Distal Medium Vessel Occlusions of the Middle Cerebral Artery
Article information
Abstract
Purpose
Mechanical thrombectomy (MT) for distal medium vessel occlusions (DMVOs) in the middle cerebral artery (MCA) is less established than for large vessel occlusions. This study evaluates the safety and efficacy of MT in DMVOs, comparing it with M1-segment occlusions.
Materials and Methods
This retrospective study analyzed 218 patients who underwent MT for isolated M1 (n=123) or distal M2+M3 (n=35) occlusions between January 2020 and August 2023. Outcomes included procedural complications, hemorrhagic events, reperfusion rates, and clinical severity and disability at admission and discharge. Multivariate logistic regression identified predictors of favorable outcomes (modified Rankin Scale≤2) at discharge.
Results
Median admission National Institutes of Health Stroke Scale (NIHSS) scores were higher in the M1 group (13, interquartile range [IQR]: 8) compared to the distal M2+M3 group (8, IQR: 7; P<0.001), with significant improvements at discharge in both groups (6 [IQR: 8] for M1 and 2.5 [IQR: 5] for M2+M3; P=0.025). Favorable outcomes were more frequent in the M2+M3 group (50.0%) compared to M1 (28.1%; P=0.023). Recanalization rates (modified Thrombolysis in Cerebral Infarction≥2b) were excellent (>90% in both groups; P=0.300). Procedural complications were rare, with vessel perforations occurring infrequently (M1: 1.6%; M2+M3: 2.9%; P=0.531). Symptomatic intracranial hemorrhage rates were similarly low (2.4% vs. 2.9%; P=0.889). Multivariate analysis identified younger age (P=0.045) and lower NIHSS (P=0.061) as predictors of favorable outcomes in distal occlusions.
Conclusion
MT is safe and effective for DMVOs of the MCA, demonstrating significant improvements in clinical outcomes and comparable complication rates to MT for M1-segment occlusions. Given the typically less severe presentations in DMVO and similar risk profiles, careful patient selection and individualized treatment remain critical.
INTRODUCTION
Acute ischemic stroke (AIS) is a significant cause of morbidity and mortality worldwide [1]. In the acute phase of AIS, prompt restoration of blood flow to the affected region of the brain is crucial to minimize damage [2]. While mechanical thrombectomy (MT) has demonstrated its efficacy in treating proximal large vessel occlusions (LVOs), its role in treating distal medium vessel occlusions (DMVOs) is yet to be established as a standard of care [2-4].
DMVOs are heterogeneously defined, but they typically include the M2 (non-dominant or distal), M3/M4, A2/A3, and P1-P3 segments and account for a substantial proportion of AIS cases (25–40%) [5,6]. While intravenous thrombolysis is generally more effective for distal, smaller cerebral vessels, it’s important to note that nearly half of the patients with such distal occlusions do not achieve early reperfusion after intravenous tissue plasminogen activator (tPA) administration alone [7]. Given that DMVOs can result in severe neurological impairments and lasting disabilities, even with the best conservative management currently available, the need for effective treatments is critical [8-10].
Recent studies have suggested that MT may be a promising treatment option for patients with DMVOs. However, prior to release of the ongoing DMVO-studies the evidence supporting the use of MT in this patient population is still limited [11]. In addition, concerns persist regarding the perceived higher risk of complications in MT for distal occlusions due to anatomical challenges, including smaller vessel calibers and increased tortuosity [5,12]. To address these gaps in knowledge, this study compares the safety and efficacy of MT for DMVOs in distal M2 and M3 segments with that for the more established M1 segment.
MATERIALS AND METHODS
In this retrospective, single-center case series, we systematically reviewed consecutive patients with isolated, primary occlusions of the M1, distal M2, or M3 segments of the middle cerebral artery (MCA), treated with MT at Westpfalz-Hospital Kaiserslautern from January 2020 to August 2023. Additionally, we included and analyzed data from patients with occlusions of the proximal M2 segment in a distinct sub-group analysis. Patients were grouped according to the location of their occlusion, with distal M2 and M3 combined into a single group. Segment definitions are detailed in Supplementary Fig. 1.
In our department, patients with a National Institutes of Health Stroke Scale (NIHSS) score of ≥4 are considered eligible for MT. Additionally, patients with an NIHSS score of <4 are also eligible if they present with clearly disabling symptoms. Advanced age, comorbidities, baseline functional status, and poor vascular anatomy are not rigid exclusion criteria for MT and are evaluated on a case-by-case basis after multidisciplinary team discussions. Patients with a known symptom onset beyond 24 hours prior to hospital presentation or those with an absent penumbra on perfusion imaging were not offered MT. The study-specific selection process is shown in Supplementary Fig. 2.
Data collected for each patient included standard patient demographics (age and sex), cerebrovascular risk factors (diabetes, dyslipidemia, atrial fibrillation, and hypertension), clinical severity and functional disability at time of admission and at discharge, administration of recombinant tPA (rtPA), time intervals, length of stay, reperfusion outcome as well as peri- and postprocedural complications.
Clinical severity and functional disability were evaluated using the NIHSS and the modified Rankin Scale (mRS) by a qualified neurologist at the time of admission and discharge. Additionally, the Alberta Stroke Program Early CT Score (ASPECTS) was utilized to assess initial ischemic changes, with scores obtained from the admission computed tomography (CT) scans. Reperfusion outcomes were assessed using the modified Thrombolysis in Cerebral Infarction (mTICI) scale, with scores determined by the operator at the end of the procedure. Successful recanalization was defined as mTICI ≥2b.
The incidence of periprocedural complications, including dissections and vessel perforations, was documented, along with the postprocedural prevalence of parenchymal bleeding, symptomatic intracranial hemorrhages (sICH), and death. Bleeding types were classified according to the ECASS-II trial as hemorrhagic infarction type 1 (HI1, small petechial hemorrhages), hemorrhagic infarction type 2 (HI2, confluent petechial hemorrhages), parenchymal hemorrhage type 1 (PH1, blood clots in <30% of the infarcted area with mild or no mass effect), and parenchymal hemorrhage type 2 (PH2, blood clots in >30% of the infarcted area with significant mass effect). sICH was defined as any hemorrhage visible on CT, combined with clinical deterioration or an increase in NIHSS score of ≥4 points [13].
Routine CT imaging was performed within 24 hours post-procedure and subsequently according to clinical need. In cases of clinical deterioration, immediate CT imaging was undertaken.
The analyzed time intervals included the duration from last well seen to groin puncture, from imaging to groin puncture, and procedure length (time from groin puncture to final angiographic series).
The primary objectives of this study were to assess the safety and feasibility of MT for DMVOs in the MCA and to compare these with the well-established MT for M1 segment occlusions.
All thrombectomies were performed under general anesthesia, with the choice of revascularization approach left to the neurointerventionist’s discretion. All procedures adhered to the principles of the 2013 Helsinki Declaration and its subsequent amendments. The study received approval from the local ethics committee. Given the retrospective design of the study, the requirement for informed consent was waived. We anonymized patient information that could identify an individual.
Quantitative variables were presented as mean±standard deviation or median (interquartile range [IQR]) and compared using either the Student’s t-test or Mann-Whitney U-test. Categorical variables were expressed as numbers and percentages, and between-group comparisons were made using the chi-squared test or Fisher’s exact test as appropriate, with the latter used for cell frequencies less than 5. Multivariate analysis to identify predictors of favorable outcomes (mRS≤2) was performed using logistic regression models, with results expressed as odds ratios (ORs) and 95% confidence intervals (CIs). A significance level of p<0.05 was assumed. Statistical analysis was performed using IBM SPSS ver. 25.0 software (IBM Co.).
RESULTS
In this study, a total of 218 patients were included: 123 with M1-segment occlusions, 35 with distal M2 or M3 occlusions, and an additional subgroup of 60 patients with proximal M2 occlusions analyzed separately. Compared between M1 and distal M2+M3 groups, the use of rtPA was similar (40.7% vs. 48.6%, P=0.403; Table 1). Stroke severity was higher in the M1 group, with a median NIHSS of 13 (IQR: 8) compared to 8 (IQR: 7) in the distal M2+M3 group (P<0.001). The median ASPECTS was significantly higher in the distal M2+M3 group (10 [IQR: 1] vs. 9 [IQR: 2], P=0.042).
Baseline characteristics
Both groups demonstrated significant clinical improvement from admission to discharge (Wilcoxon P<0.001 for both) (Table 2). In the M1 group, NIHSS improved from 13 (IQR: 8) to 6 (IQR: 8), while in the distal M2+M3 group, NIHSS decreased from 8 (IQR: 7) to 2.5 (IQR: 5, P=0.025). However, the median change in NIHSS did not differ significantly between groups.
Treatment data, clinical outcomes, and complications
Pre-stroke functional impairment (mRS≥3) was observed more frequently in the M1 group (22.0%) than in the distal M2+M3 group (8.6%, P=0.075). Among patients with a prestroke mRS≤2, favorable outcomes at discharge (mRS≤2) were significantly more frequent in the distal M2+M3 group (50.0%) compared to the M1 group (28.1%, P=0.023; Supplementary Fig. 3).
Recanalization rates (mTICI≥2b) were excellent in both groups: 97.1% for distal M2+M3 vs. 90.2% for M1 (P=0.300). First-pass mTICI 3 success rates were also comparable (34.3% for distal M2+M3 vs. 43.9% for M1; P=0.338). The average number of maneuvers required for recanalization was similar (1.75±1.14 for M1 vs. 1.63±0.84 for distal M2+M3; P=0.228), as were the rates of aspiration-only thrombectomy (17.9% for M1 vs. 17.1% for distal M2+M3; P=0.919). Rescue stenting was performed exclusively in the M1 group (3.3%).
Procedural timing metrics revealed that the interval from imaging to groin puncture was significantly longer in the distal M2+M3 group compared to the M1 group (116.74±89.09 minutes vs. 93.84±39.98 minutes; P=0.032). The total time from stroke onset to groin puncture was slightly longer in the distal M2+M3 group (313.50±272.63 minutes) compared to the M1 group (230.20±93.66 minutes), although this difference was not statistically significant (P=0.154). Procedure duration was marginally longer in the M1 group, approaching significance (55.51±46.80 minutes for M1 vs. 44.80±21.84 minutes for distal M2+M3; P=0.058).
Procedural complications were infrequent in both groups. There were 2 instances of vessel perforation in the M1 group (1.6%) and 1 case in the distal M2+M3 group (2.9%) (P=0.531). Vessel dissections occurred exclusively in the M1 group, with 2 cases (1.6%, P>0.999).
Hemorrhagic complications were generally infrequent across both groups. Rates of sICH were similar, with 2.4% in the M1 group and 2.9% in the distal M2+M3 group (P=0.889). There were no significant differences in individual parenchymal hematoma subtypes. Hemorrhagic infarction type 1 (HI1) was reported exclusively in the M1 group (3.3% vs. 0%; P=0.576), whereas hemorrhagic infarction type 2 (HI2) occurred more frequently in the distal M2+M3 group (11.4% vs. 3.3%; P=0.073).
Mortality rates were slightly lower in the distal M2+M3 group (14.3%) compared to the M1 group (21.1%), but this difference was not statistically significant (P=0.368).
The subgroup analysis comparing proximal M2 occlusions to distal M2+M3 occlusions showed no significant differences in clinical outcomes or complication rates. Both groups demonstrated similar improvements in neurological function and rates of favorable outcomes at discharge. Procedural safety, as measured by hemorrhagic and other complications, was also comparable across these occlusion sites (Table 3).
Clinical outcome and complication rates of proximal M2 occlusions in comparison to distal M2+M3 occlusions
Multivariate Analysis
In the M1 group (n=96), significant predictors of favorable outcomes included lower NIHSS scores at admission (OR: 0.686, 95% CI: 0.547–0.859, P=0.001), younger age (OR: 0.891, 95% CI: 0.811–0.980, P=0.017), and the use of aspiration-only techniques (OR: 15.482, 95% CI: 2.307–103.902, P=0.005). The number of maneuvers was inversely associated with favorable outcomes, with fewer maneuvers significantly improving the likelihood of recovery (OR: 0.192, 95% CI: 0.071–0.521, P=0.001). Atrial fibrillation was also associated with favorable outcomes (OR: 6.147, 95% CI: 1.142–33.074, P=0.034). Other variables, including ASPECTS, hypertension, diabetes, and imaging-to-puncture time were not significantly associated with favorable outcomes.
In the distal M2+M3 group (n=32), younger age was significantly associated with favorable outcomes (OR: 0.862, 95% CI: 0.746–0.997, P=0.045). Lower NIHSS scores at admission showed a strong trend toward significance (OR: 0.716, 95% CI: 0.505–1.015, P=0.061). Other variables, including the number of maneuvers, ASPECTS, and the use of aspiration-only techniques were not significantly associated with favorable outcomes.
For the proximal M2 group (n=51), lower NIHSS scores at admission were associated with higher odds of recovery (OR: 0.836, 95% CI: 0.699–1.000, P=0.050). Younger age (OR: 0.906, 95% CI: 0.824–0.996, P=0.041) and higher ASPECTS (OR: 2.896, 95% CI: 1.167–7.187, P=0.022) were also significant predictors. The number of maneuvers was inversely associated with favorable outcomes, with fewer maneuvers increasing the likelihood of recovery (OR: 0.257, 95% CI: 0.103–0.643, P=0.004).
DISCUSSION
This retrospective, single-center case series demonstrates the feasibility and safety of MT for DMVOs of the MCA, specifically the distal M2 and M3 segments. Our findings add to the growing body of evidence supporting MT as an effective intervention for DMVOs, which have traditionally been less established as targets for thrombectomy compared to LVOs.
In our study, both the M1 and distal M2+M3 groups demonstrated good recanalization rates exceeding 90%, with a similar number of maneuvers required in each group and a first-pass mTICI3 rate of 43.9% and 34.4%, respectively. Both groups showed significant clinical improvement between admission and discharge, reflected by reductions in NIHSS scores. The distal M2+M3 group achieved a higher proportion of favorable functional outcomes (mRS≤2 at discharge) compared to the M1 group (Table 2). This disparity likely stems from the lower stroke severity at admission in the distal group (median NIHSS: 8 vs. 13, P<0.001) and the lower prevalence of pre-existing functional impairments in these patients. This, however, may hint at a potential selection bias. Patients with better baseline functional status or lower prestroke morbidity may have been preferentially selected for distal thrombectomy, potentially skewing outcomes towards more favorable pre-stroke functional profiles in the distal group.
Across all occlusion groups, lower NIHSS scores at admission and younger age consistently emerged as key predictors of favorable functional outcome (Table 4). The number of maneuvers was inversely associated with recovery across all groups but showed particular significance in the proximal M2 group. In the M1 group, the use of aspiration-only techniques was notably associated with better outcomes, suggesting potential advantages of simpler procedural approaches. In the distal M2+M3 group, the limited number of aspiration-only thrombectomies (n=6) precludes definitive conclusions regarding its efficacy. However, evidence from the broader literature suggests that direct aspiration first-pass techniques may offer comparable or even superior outcomes to combined stent-retriever/aspiration approaches in certain cases [14].
Multivariate logistic regression analysis for predictors of favorable outcomes (mRS≤2) at discharge
The distal M2+M3 group experienced a longer duration from imaging to groin puncture. This delay is likely due to the higher threshold for initiating intervention in distal occlusions, as MT for these cases is not yet consistently recommended in current guidelines [3]. Furthermore, peripheral occlusions are more challenging to detect and often require advanced imaging modalities, such as perfusion imaging, for confirmation. This diagnostic challenge may have contributed to the extended time intervals observed in the distal group [15]. Additionally, the total time from symptom onset to groin puncture was longer in the distal group, although this difference did not reach statistical significance. This trend could also partially be explained by the lower clinical deficit often associated with distal occlusions, which might have delayed hospital presentation by the patients.
It is assumed that the complication risk associated with MT might be higher for distal occlusions due to their longer, more tortuous access routes and thinner arterial walls, as these factors can potentially increase the risks of dissection, perforation, and vasospasm during mechanical manipulation [5]. This heightened risk profile is particularly concerning given that distal occlusions typically show less severe deficits, implying that patients could experience significant detriment from any procedural complications. Despite these concerns, vessel perforation rates in our study were low and did not differ significantly between groups, occurring in 1.6% of M1 cases and 2.9% of M2+M3 cases. This may, however, suggest a trend, as prior studies have reported higher perforation rates in medium vessel occlusions compared to LVOs [16].
The incidence of sICH remained low and similar between groups, with 2.4% in the M1 group and 2.9% in the M2+M3 group. Similarly, the rates of PH1 and PH2 did not differ significantly between groups. However, there was a tendency toward higher rates of HI2 in the M2+M3 group. This trend may be partially explained by the longer imaging-to-groin and onset-to-groin times observed in the distal group, which could result in more pronounced ischemic damage and blood-brain barrier disruption, thereby increasing the risk of reperfusion injury. Additionally, the differentiation between HI1 and HI2 may be less distinct in smaller infarct areas, where petechial hemorrhages can be more challenging to classify accurately. While HI2 is generally asymptomatic and does not cause immediate clinical deterioration, evidence from studies primarily focused on LVO indicates that even asymptomatic hemorrhages, including HI2, might be associated with worse functional outcomes [17]. The relevance of this finding for distal vessel occlusions remains unclear.
In a subgroup analysis comparing clinical outcomes and complication rates between proximal M2 and distal M2+M3 occlusions, we found a consistent safety profile regarding hemorrhagic and procedural complications, as well as similar improvements in NIHSS scores and rates of favorable outcomes at discharge (Table 3). These findings indicate that, within the scope of this analysis, thrombectomy demonstrates comparable efficacy and safety between these specific occlusion sites.
Our study has several limitations that should be considered. As a retrospective, single-center case series, the findings may not be generalizable to other centers with different thrombectomy practices or patient populations. Additionally, the small sample size, particularly in the distal M2+M3 group, limits the statistical power of our analyses, especially for detecting rare complications such as sICH. The mTICI scale was originally developed for LVOs and may not fully capture the specific anatomical and procedural nuances of distal M2 and M3 occlusions. For example, partial reperfusion prior to thrombectomy in distal occlusions could already meet mTICI 2b criteria, potentially overestimating procedural success. The absence of a control group receiving medical treatment alone and variations in thrombectomy techniques further limit the generalizability of our findings. Additionally, there is potential for selection bias, as patients with higher disability or more accessible occlusion sites may have been preferentially selected for MT. Lastly, our study’s short observation period, which concluded at hospital discharge, could lead to an underestimation of long-term functional outcomes and does not provide insights into post-discharge mortality rates.
CONCLUSION
In summary, our study supports the safety and efficacy of MT for DMVOs of the MCA. High recanalization rates and significant neurological improvements were observed, with complication rates comparable to those seen in M1-segment occlusions. However, distal occlusions typically present with less severe deficits, implying that patients could experience significant detriment from procedural complications, highlighting the need for careful patient selection.
Future studies with randomized controlled designs are needed to validate our findings and provide a more comprehensive understanding of the efficacy and safety of MT for DMVOs.
SUPPLEMENTARY MATERIALS
Supplementary materials related to this article can be found online at https://doi.org/10.5469/neuroint.2024.00500.
Schematic representation of the MCA segments. The M1 segment extends from the internal carotid artery to the bifurcation. The proximal M2 segment begins at the bifurcation and continues up to the mid-height of the insular cortex, with the distal M2 segments following beyond this point. M3 branches extend horizontally toward and along the Sylvian fissure. MCA, middle cerebral artery.
Study population flowchart. MCA, middle cerebral artery.
Distribution of mRS scores before stroke onset and at discharge, excluding patients with pre-stroke mRS≥3. mRS, modified Rankin Scale.
Notes
Fund
None.
Ethics Statement
The study was conducted in accordance with the Declaration of Helsinki and received approval from the local Ethics Committee of Rhineland-Palatinate, Germany (no. 2022-16455-retrospektiv). Due to the retrospective nature of the study, informed consent was waived. We anonymized patient information that could identify an individual.
Conflicts of Interest
The authors have no conflicts to disclose.
Author Contributions
Concept and design: MCB, WN. Analysis and interpretation: MCB, PD. Data collection: MCB. Writing the article: MCB. Critical revision of the article: AS, PD, WN. Final approval of the article: MCB, AS. Statistical analysis: MCB. Obtained funding: none. Overall responsibility: AS.