Introduction

Basilar artery occlusion (BAO) is uncommon. It accounts for about 1% of all strokes.1 Despite recent advances in the treatment of acute stroke, prognosis remains poor with a high mortality rate in patients with BAO, especially in the absence of early reperfusion.2

Recanalization is a strong predictor for clinical outcome and infarct volume after thrombolytic treatment.3 4 Several factors associated with successful recanalization have been reported. Underlying pathologic subtypes of BAO, collateral status, site of occlusion and first-line strategy have been known to be associated with differing recanalization rates in the setting of acute BAO.2 4–6 Only a small number of previous studies based on thrombolytic treatment have shown the correlation between the angiographic morphologic features of the clot and recanalization. In these investigations, angiographic ‘tram-track’ and ‘outline’ appearing in the occlusion site before treatment showed higher rates of successful recanalization.5–7 However, literature on the association of the morphologic features of the clot and treatment outcome in relation to modern mechanical thrombectomy (MT) is scarce.8 9 Meniscoid or side-wall contrast opacification at the occlusion site is a descriptive finding similar to the ‘tram track’ or the ‘outline’ sign, often encountered on angiography during intra-arterial reperfusion therapy. These findings may help predict the characteristics of the clot, the treatment outcomes and establish treatment plans.

We hypothesized that the results of MT would be affected by the initial angiographic morphology of the occlusive lesion. We therefore evaluated the clinical significance of the clot meniscus sign in acute BAO patients treated by MT.

Patients and methods

Patients

A retrospective review of a prospective registry of all consecutive acute ischemic stroke patients referred for MT to a tertiary hospital between March 2010 and December 2018 was used as the study cohort. The Institutional Review Board approved this study and waived written informed consent based on the retrospective study design.

The following inclusion criteria were used: (1) patients who showed acute neurologic symptoms attributable to BAO identified by CT angiography (CTA); (2) time from onset of symptoms to groin puncture of ≤12 hours; (3) baseline National Institutes of Health Stroke Scale (NIHSS) score ≥4; (4) no intracranial hemorrhage detected on initial CT; (5) MT by using stent retriever or contact aspiration thrombectomy as the primary treatment. Exclusion criteria included BAO caused by other causes such as arterial dissection, vasculitis or Moyamoya disease. The patients were routinely evaluated for the determination of stroke etiology, which included echocardiography, continuous electrocardiography monitoring in the stroke unit or Holter monitoring, and cardiac CT. The etiology of stroke was determined based on consensus among stroke specialists in weekly stroke conferences.

During this study period, 735 acute ischemic stroke patients with large vessel occlusion were referred for endovascular therapy. One hundred and four patients who underwent endovascular treatment for acute BAO were initially enrolled. Among them, 10 patients with occlusion due to dissection (n=7; basilar artery (BA) dissection n=2, vertebral artery (VA) dissection extending into BA n=5) or vasculitis (n=3) were excluded. Patients were also excluded if the angiography was not available or sufficient for review (n=5). The remaining 89 patients were included in the final analysis (figure 1).

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Figure 1

Flow diagram of the current study. CTA, CT angiography; NIHSS, National Institutes of Health Stroke Scale.

Image analysis

Two interventional neuroradiologists (DJK and SHB; 17 and 3 years of experience, respectively) independently evaluated all the images. The investigators were blinded to the clinical outcome during image analysis. The clot meniscus sign was defined as: (1) meniscoid/edge-like appearance at the proximal occlusion site, or (2) tram-track like appearance/antegrade side-wall contrast opacification distal to thrombus on the arterial phase image of the presenting initial angiography (figure 2). All other findings such as fading/tapering and abrupt cut-off were considered as absence of the clot meniscus sign (figure 3). The evaluations of the clot meniscus sign were performed on cerebral angiography images which were selected from the arterial phase with best vessel contrast. Cerebral angiography was performed on a biplanar Allura Xper FD scanner (Philips Healthcare).

The location of BAO was divided into proximal (from the vertebrobasilar junction to the origin of the anterior inferior cerebellar artery), middle (from the origin of the anterior inferior cerebellar artery to the origin of the superior cerebellar artery), and distal occlusion (distal to the origin of the superior cerebellar artery) according to the cerebral angiography findings.1 10 On preprocedural CTA, calcification of the vessel wall was considered present when it was noted in situ or proximal to the occlusion site on CTA. Discordance between two readers was resolved by consensus.

Endovascular treatment

All procedures were performed by two interventional neuroradiologists (DJK and BMK; 17 and 16 years of experience, respectively). Before the procedure, the CTA images were reviewed for evaluation of the site of the occlusion and the access route. The details of the techniques used for stent retriever or contact aspiration have been described previously.11 In general, the procedure was performed via the femoral approach by using a 6 F shuttle sheath and/or a 5 or 6 F guiding/intermediate catheter for access into the VA. The first-line device for MT was chosen at the operator’s discretion—either a stent retriever (Solitaire (Covidien, Irvine, California) or Trevo stent (Stryker, Kalamazoo, Michigan)) or contact aspiration with large-bore aspiration catheter (Penumbra (Penumbra, Alameda, California) or 5 F SOFIA intermediate catheter (MicroVention, Tustin, California) or AXS Catalyst six intermediate catheter (Stryker Neurovascular, Mountain View, California))—with the possibility of switching to another strategy (rescue treatment) in case of reperfusion failure with the first approach. Adjuvant treatment using balloon and/or stent angioplasty in patients with underlying BA in situ atherosclerosis or tandem lesions and intra-arterial tirofiban/urokinase infusion for recurrent/residual thrombosis, or lesion access failure were performed.

Outcome measures

Clinical data recorded for the study, including sex, age, vascular risk factors (hypertension, hypercholesterolemia, diabetes mellitus, smoking, atrial fibrillation, coronary disease), baseline NIHSS score, intravenous recombinant tissue plasminogen activator (rtPA) therapy, time intervals (ie, onset, puncture, recanalization time), 90-day modified Rankin Scale (mRS) score, hemorrhage and mortality, were collected. The procedure time was defined as the time from puncture to final recanalization in successful recanalization patients and time of the last angiographic series in unsuccessful recanalization patients. Recanalization status was assessed on the final angiogram and was classified according to the modified Thrombolysis in Cerebral Infarction (TICI) scale; successful recanalization was defined as modified TICI grades 2b or 3.12 First pass effect (FPE) was defined as achieving complete recanalization (mTICI 3) with a single thrombectomy device pass. Favorable clinical outcome was defined as a 90-day mRS score of 0–2. A non-enhanced brain CT or MRI was routinely performed in the first 24 hours after the procedure. An intracerebral hemorrhage was classified according to the second European-Australasian Acute Stroke Study classification, and symptomatic intracerebral hemorrhage was defined as any hemorrhage associated with an NIHSS score increase ≥4 within 24 hours.13

Statistical analysis

Statistical analyses were performed by using SPSS for Windows (version 20.0; IBM, Armonk, New York) and R (version 3.5.1; R Foundation for Statistical Computing, Vienna, Austria). Inter- and intra-reader agreement for presence or absence of clot meniscus sign was assessed by using the Cohen κ statistics, with a κ of 0.81–1.00 corresponding to almost perfect agreement; 0.61–0.80, substantial; 0.41–0.60, moderate; 0.21–0.40, fair; 0.00–0.20, slight; and <0.00, poor agreement. To assess intra-reader agreement, readers performed a second reading session of the dataset 3 months later to minimize recall bias. The baseline characteristics and clinical outcomes between the patients with the clot meniscus sign (positive meniscus group) and those without the clot meniscus sign (negative meniscus group) were compared. Pearson χ² test or Fisher exact test was used for categorical variables, and the Mann-Whitney U test for continuous variables. Multivariable logistic regression was performed to evaluate the independent variables for successful recanalization and favorable clinical outcome separately. A value of p<0.05 was considered statistically significant.

Results

Baselines characteristics are provided for the overall study sample according to the presence or absence of the clot meniscus sign (table 1). The clot meniscus sign was diagnosed in 62.9% (53/89) of the patients with acute BAO. For the presence or absence of the meniscus sign, we found an excellent inter-reader and intra-reader agreement (κ values, 0.87, 95% CI 0.74 to 1.0, and 0.92, 95% CI 0.87 to 0.95, respectively). Atrial fibrillation was more frequent in the meniscus sign (+) group but did not reach statistical significance (42.9% vs 24.2%, p=0.077). Proximal BA occlusions were more frequent in the meniscus sign (−) group (p<0.001), whereas distal BA occlusions were more frequent in the meniscus sign (+) group (p<0.001). Calcification on pretreatment CTA was more frequently observed at the BAO site in the meniscus sign (−) group (28.6% vs 52.5%, p=0.003). Other baseline factors did not show significant differences between the groups.

The treatment and clinical outcomes are summarized in table 2. Overall, successful recanalization was achieved in 79.8% (71/89) of the patients and a favorable clinical outcome in 33.7% (30/89) of the patients. The meniscus sign (+) group showed a shorter procedure time (55 vs 85 min; p=0.045), higher rate of successful recanalization (89.3% vs 63.6%, p=0.004), higher incidence of first pass effect (89.3% vs 63.6%, p=0.004), and lower total number of passes (median, 2 vs 3; p=0.042) when compared with the meniscus sign (−) group. A favorable clinical outcome was more frequently achieved in the meniscus sign (+) group but did not reach statistical significance (39.3% vs 24.2%; p=0.147). There was no significant difference in the incidence of mortality and hemorrhagic complications between the groups. The successful recanalization rates were higher in the meniscus sign (+) group compared with the meniscus sign (−) group irrespective of the location of the occlusion (table 3).

Multivariate logistic regression analysis showed that the procedure time (OR 0.972, 95% CI 0.962 to 0.992; p=0.003) and the clot meniscus sign (OR 7.920, 95% CI 1.769 to 35.452; p=0.007) were independent predictors of successful recanalization when adjusting for age, baseline NIHSS score, intravenous tPA, occlusion site, calcification on CTA and first-line MT strategy (table 4). Baseline NIHSS score (OR 0.796, 95% CI 0.709 to 0.894; p<0.001) and procedure time (OR 0.969, 95% CI 0.945 to 0.994; p=0.016) were significantly associated with favorable clinical outcome after adjusting for relevant covariates.

Discussion

This study shows that the MT treatment outcomes for patients with acute BAO were different according to the angiographic morphological feature of the occlusive lesion. The presence of the clot meniscus sign was associated with higher first-pass/successful recanalization rates and less total number of passes, less adjuvant treatment and shorter procedure time. The clot meniscus sign was an independent predictor of successful recanalization.

Morphological analysis of the occlusive lesion to predict the efficacy of thrombolytic therapy has been performed in a small number of studies.5 7 14 However, literature on the association between the angiographic occlusive lesion morphology and MT in relation to the treatment device, etiology and outcome is scarce.9 15 Occlusion of the parent artery has been described using many different terms such as cut-off, tapered, meniscoid, tram track, blurred/sharp, claw sign and regular/irregular.5 7 9 14 15 The definitions of the meniscus sign, claw sign, and outline/tram track sign share similarities shown on angiography as filling defects with side wall opacification. However, these terms can be subjective and may be influenced by the orientation, curvature and branching patterns of the underlying occluded parent vessel.7 By definition our ‘meniscus sign’ incorporated all ranges of convex filling defects from those showing convex protrusion less than half of the diameter (excluded in the claw sign) to those showing longer side wall opacification (tram track sign). The value of such imaging features may be more significant when limited to the basilar artery, which shows a relatively straight and consistent configuration compared with the M1. In this regard, we have used a simplified dichotomization into either meniscus sign (+) or meniscus sign (−) in BAOs and showed an excellent inter- and intra-reader agreement. Also, the incidence of underlying in-situ intracranial atherosclerosis (ICAS) is higher in the posterior circulation compared with the anterior circulation, reaching up to about 40%, which may allow a more balanced representation of the underlying cause.16 17 Nonetheless, based on our results in the BAO, we believe that the meniscus sign can be applied to other arteries and should be validated in future studies.

In our study, the patients with the meniscus sign showed significantly higher frequency of distal basilar artery occlusion. On the other hand, the patients without the meniscus sign showed a significantly higher frequency of proximal occlusion and adjacent arterial wall calcifications. Distal BAOs are often associated with an embolic etiology whereas calcifications of the arterial wall suggest an underlying in situ ICAS.6 18 19 Other authors have shown that imaging features similar to the meniscus sign are associated with embolism as the cause of the occlusion.9 These results suggest that the meniscus sign may be associated with an embolic occlusion rather than an in situ ICAS-related occlusion. Our results also coincide with previous studies suggesting that embolic occlusions are associated with higher recanalization rates than ICAS-related BAO when treated by MT.6 17 20 The meniscus sign also showed a consistently higher recanalization rate irrespective of the location of the occlusion, suggesting the efficacy of this simple and practical imaging biomarker. This predictability of recanalization success and the differentiation of the etiology of the occlusion based on the meniscus sign in the BAO has significant clinical implications, considering the higher incidence of underlying ICAS in the posterior circulation.16 17Patients with underlying ICAS lesions often require more complicated adjuvant therapy and thus a longer procedural time as seen in our series, which can significantly influence endovascular treatment planning.

Various factors can influence the interaction between the device, the thrombus and the vessel wall during MT.21 22 In our meniscus sign (+) group, the clot may have more area available for contact with the MT device and less area of contact with the vessel wall. It may also allow an easier and wider area for engagement by the thrombectomy device and impose less friction/adhesion between the thrombus and the vessel wall. Thus, the morphological features of the clot such as the meniscus sign could be a favorable marker for an easy-to-remove thrombus.

Consoli’s classification into regular/irregular phenotypes is an interesting but different approach. Contrary to our meniscus and other morphologic classifications such as Yamamoto’s claw sign, Consoli’s regular/irregular occlusions do not differ in terms of overall recanalization rates (88.8% vs 81.8%, p=0.22).9 15 However, it showed that the irregular M1 occlusions were associated with better procedural and clinical outcomes when treated with the stent retriever compared with contact aspiration. The baseline characteristics and causes of stroke between the regular/irregular occlusions did not show any differences, suggesting that this classification provides a biomarker for discriminating the effectiveness of either the stent retriever or contact aspiration—hypothetically based on the consistency of the clot—rather than the underlying etiology of the occlusion.8 9 15

Our study showed that the presence of the clot meniscus sign was an independent factor for successful recanalization, but only low admission NIHSS and short procedure time were associated with favorable clinical outcomes in multivariable analysis. The favorable clinical outcome rates were higher in the meniscus sign (+) group but did not reach statistical significance. Results of earlier studies on acute vertebrobasilar occlusions have identified the initial severity of neurologic deficits, time to treatment, location of the occlusion, degree of collaterals, treatment modalities, and timely reperfusion as the prognostic factors.2 18 23 Among these, recanalization seems to be the most important and improves survival; however, it does not guarantee a good outcome.24 One of the main causes of this disassociation between the recanalization rate and clinical outcome may be due to the underlying differences between the posterior and the anterior circulation. Compared with the anterior circulation, the damage from a BAO results mainly from perforator territory injury which lacks collaterals, and thus may be more susceptible to time. In the Basilar Artery International Cooperation Study (BASICS), none of the basilar artery occlusion patients with severe deficits had a good outcome when treatment was started beyond the 9 hour time window.25 Despite these differences, the time window for treatment in the posterior circulation had often been extended due to the known poor natural history of this disease. Newer techniques and devices may have improved the recanalization and mortality rates in these patients; however, the selection of patients who can achieve a good outcome is another essential issue. Imaging-based identification of the initial extent of the core may be helpful in selecting patients who will benefit from MT.26

This study had some limitations. Due to the retrospective design, the MT device was chosen at the discretion of the operator and thus there may be bias. Second, the sample size was relatively small to investigate differences such as the efficacy of various MT devices between the subgroups of this cohort. Future studies in a larger cohort are warranted.

Conclusion

In conclusion, the angiographic morphologic feature of the occlusive lesion in acute BAO patients is associated with MT outcome and may have therapeutic implications. The clot meniscus sign is related to high first pass effect and short procedure time, and is a reliable predictor of successful recanalization. Patients without the clot meniscus sign are associated with more frequent adjuvant treatment and increased procedural time.

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Figure 2

Basilar artery occlusion with a clot meniscus sign. The patient presented with dysarthria and dizziness for 3 hours. (A) Left vertebral artery anteroposterior angiogram shows the meniscoid appearance of clot occlusion at the middle segment of the basilar artery. (B) Anteroposterior image shows distal navigation of microwire beyond the occlusion site. (C) Anteroposterior native image shows deployment of the stent retriever (Trevo, 4/20 mm) covering the occluded segment. (D) After a single attempt of stent retrieval, complete recanalization of the basilar artery without residual stenosis is seen.

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Figure 3

Basilar artery occlusion without a clot meniscus sign. The patient presented with mental change for 4 hours. (A) Left vertebral artery angiogram shows the tapered appearance of a clot occlusion at the middle segment of the basilar artery. (B) Anteroposterior angiogram demonstrates contact aspiration with a large-bore aspiration catheter (Penumbra, 041 inch). (C) Basilar artery recanalization was achieved after two trials of contact aspiration and additional intra-arterial urokinase (200000 IU) (not shown). Severe underlying atherosclerotic stenosis in mid basilar artery was revealed. (D) Reocclusion of the lesion with impaired distal flow was seen on 10 min delayed angiogram despite additional intra-arterial administration of tirofiban (0.5 mg). (E) Balloon angioplasty (Ryujin Plus, 2.5/10 mm) was performed covering stenotic portion. (F) Final angiogram shows recanalization with underlying atherosclerotic stenosis.