Introduction

Endovascular therapy (EVT) dramatically improves clinical outcomes for patients with emergent large vessel occlusion (ELVO). The Society of NeuroInterventional Surgery (SNIS) Standards and Guidelines Committee updates and supplements the existing SNIS guideline ‘Current endovascular strategies for posterior circulation large vessel occlusion stroke’.1–3 Acute ischemic stroke within the posterior circulation accounts for up to 20% of ischemic stroke diagnoses. Patients with a large vessel occlusion of the vertebral or basilar artery are now often treated with endovascular thrombectomy. This document provides recommendations for the treatment of these patients.

Posterior circulation large vessel occlusion strokes

Basilar artery occlusion (BAO) accounts for approximately 1% of all ischemic strokes and about 10% of strokes due to an intracranial large vessel occlusion.4 Although this condition may be relatively uncommon, it captures our attention due to its potentially devastating consequences, which may include death or locked-in syndrome. Despite reports of high morbidity and mortality, the natural history can be quite variable, and clinical outcomes likely depend on a variety of patient factors, such as age, baseline health, severity of presenting symptoms, location of the occlusion along the basilar artery, presence of collaterals, and territory of any associated ischemic injury.5–8 Nonetheless, BAO remains one of the most dreaded types of stroke.

Similar to the transition from IMS-III (Interventional Management of Stroke III) to the post-MR CLEAN (Multicenter Randomized Clinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands) era for anterior circulation ELVO stroke treatment, new data in BAO strokes provide encouraging results regarding improved clinical outcomes. The previously reported randomized BEST (Basilar Artery Occlusion Endovascular Intervention vs Standard Medical Treatment)9 and BASICS (Basilar Artery International Cooperation Study)10 trials did not show a definite benefit of EVT over medical therapy. However, a trend towards better outcomes with thrombectomy was noted in these trials. Concerns regarding clinical equipoise and treatment crossover may have undermined these studies. In contrast, the more recent ATTENTION (Endovascular Treatment for Acute Basilar Artery Occlusion)11 and BAOCHE (Basilar Artery Occlusion Chinese Endovascular Trial)12 studies demonstrated that EVT within 0–12 and 6–24 hours of symptom onset, respectively, is superior to medical therapy.

New trial summary

The ATTENTION trial randomized acute ischemic stroke patients with BAO to best medical therapy or thrombectomy plus best medical therapy. Enrolled patients had an National Institutes of Health Stroke Scale (NIHSS) score of ≥10. The study was performed in China, and patients in ATTENTION were randomized between 0 and 12 hours from symptom onset in a 2:1 manner to EVT versus best medical therapy. In total, 226 patients were assigned to the EVT arm and 114 to the medical therapy arm.11 Good functional outcome was defined as a modified Rankin Scale (mRS) score of 0–3, 90 days after symptom onset; this was achieved in 46% of the EVT group versus 23% in the medical therapy group (absolute risk reduction (ARR) 2.06, 95% CI 1.46 to 2.91, P<0.001). Although the symptomatic intracranial hemorrhage rate was 5% in the thrombectomy group and 0% in the medical group, the difference did not reach statistical significance. Mortality at 90 days was lower in the EVT arm (37%) compared with the medical arm (55%, ARR 0.66, 95% CI 0.52 to 0.82). Of note, 14% of EVT cases were noted to have a procedural complication, including one death due to arterial perforation.

The BAOCHE trial was also performed in China, and this study randomized patients with acute ischemic stroke due to BAO to medical therapy or thrombectomy plus medical therapy.12 Patients in BAOCHE were enrolled 6–24 hours after symptom onset and had an NIHSS score of ≥6. The primary endpoint of a favorable clinical outcome was initially defined as mRS 0–4, but was later changed to mRS 0–3 after the study started. The trial was stopped early due to an interim analysis that demonstrated the superiority of the thrombectomy arm. When the study was halted, 110 patients had received thrombectomy and 107 had received medical therapy. Favorable outcomes (mRS 0–3) were achieved in 46% of thrombectomy patients versus 24% of medical therapy patients (ARR 1.81, 95% CI 1.26 to 2.60, P<0.001). Like ATTENTION, symptomatic intracranial hemorrhage was uncommon and non-significantly higher in the thrombectomy group (6% vs 1%, relative risk (RR) 5.18, 95% CI 0.46 to 42.18). Mortality at 90 days was also non-significantly lower in the thrombectomy group (31% vs 42%, RR 0.75, 95% CI 0.54 to 1.04). Procedural complications in thrombectomy patients occurred in 11%, which was similar to the rate in ATTENTION.

Pre-thrombectomy imaging considerations

The previously reported Basilar Artery International Cooperation Study (BASICS10 and the Basilar Artery Occlusion Endovascular Intervention vs Stanford Medical Treatment (BEST9 trials—both of which used simple imaging criteria for enrollment—failed to demonstrate the superiority of thrombectomy compared to medical therapy in patients with acute ischemic stroke due to a basilar artery occlusion. Patients had BAO on CT angiography (CTA) and a non-contrast head CT free of bleeding and free of extensive brainstem infarction, cerebellar mass effect, or acute hydrocephalus. However, there was no other quantitative assessment of ischemic injury applied. ATTENTION and BAOCHE also required demonstration of BAO on CTA, and evidence of limited ischemic injury, defined as a posterior circulation Alberta Stroke Program Early CT Score (PC-ASPECTS) of ≥6 (figure 1).

Figure 1

Posterior circulation Alberta Stroke Program Early CT Score (PC-ASPECTS) on MRI and CT. PC-ASPECTS regions are noted on MRI (top row) and non-contrast CT (bottom row). PC-ASPECTS are assigned in the following manner: pons, 2 points; cerebellum, 1 point per hemisphere; midbrain, 2 points; thalamus, 1 point per hemisphere; and posterior cerebral artery territory in occipital lobes, 1 point per hemisphere. Note that MRI images are shown on T2 weighted images to better delineate brain anatomy, but PC-ASPECTS is assigned based on restricted diffusion on diffusion weighted images. Cer, cerebellum; T, thalamus; PCA, posterior cerebral artery territory.

Further research is required to determine the optimal imaging selection for BAO patients before thrombectomy, but at this time, the evidence suggests that eligible patients should have a PC-ASPECTS ≥6 on non-contrast head CT and BAO on CTA. The use of MRI is not required before basilar artery thrombectomy. However, this imaging modality remains helpful in the evaluation of these patients, given the greater sensitivity of the modality for ischemia within the posterior fossa, which is notoriously difficult to assess on non-contrast head CT. The role of CT perfusion techniques has shown promise in identifying patients who do and do not benefit from thrombectomy,13 and ongoing prospective studies will provide additional guidance as to the use of CT perfusion in patients with posterior circulation large vessel occlusion (LVO).

Thrombectomy technical considerations

Endovascular thrombectomy techniques generally include aspiration, mechanical thrombectomy with stentretriever devices, cervical or cerebral artery angioplasty, and cervical or cerebral artery stent placement. Adjunctive medical therapies may also be performed, which include intravenous antiplatelet medication administration and intra-arterial thrombolysis. Moreover, thrombectomy may be performed with patients undergoing moderate sedation or general anesthesia. The recently reported ATTENTION and BAOCHE trials used varied endovascular thrombectomy techniques, briefly summarized below.

In the ATTENTION trial, the thrombectomy technique was left to the treating physician’s discretion, and general anesthesia was used in 56% of treated patients. Treatment strategies included stent retrievers alone in 5%, aspiration alone in 35%, and combined aspiration and stent retriever use in 50%. Notably, intracranial angioplasty and stent placement were performed in 40%, extracranial angioplasty and stent placement in 8%, intra-arterial thrombolysis in 5%, and intravenous tirofiban administration in 40%. The specific devices and intracranial stents used in the ATTENTION trial have not been reported.

In the BAOCHE trial, the thrombectomy treatment protocol was more restricted. General anesthesia was used in 65% of patients. All patients were treated with the Solitaire SR (Medtronic), and other rescue aspiration, additional stent retrievers, and pharmacological treatment options were not allowed except in cases of cervical or cerebral artery angioplasty and stenting. Intracranial angioplasty or stenting after a failed thrombectomy was performed in 55%, the Solitaire SR was detached in 26%, and other stents were used in 12% of cases. Tirofiban was administered during the procedure in 54% of patients in the BAOCHE trial. Hemorrhagic rates were low, even in the setting of angioplasty and stenting.

In summary, all of the commonly used thrombectomy techniques (aspiration, stent retriever, and combined techniques) were performed with high frequency in the ATTENTION and BAOCHE trials. They were shown to be effective for the treatment of posterior circulation LVO. The high rates of cervical and intracranial angioplasty and stent placement, and intravenous GP2b3a inhibitor administration in the ATTENTION and BAOCHE trials likely reflects the frequency of intracranial atherosclerosis in the posterior circulation14 as well as within the Chinese population15 that comprised these studies. The use of angioplasty and stent placement with associated medical therapy was an effective treatment for posterior circulation LVO in these studies. It may be a reasonable rescue technique to consider for the emergent treatment of intracranial atherosclerosis after failed aspiration based or stent retriever based thrombectomy, despite the results of SAMMPRIS (Stenting vs Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis)16 in symptomatic intracranial atherosclerosis a decade ago. However, nearly all commonly used angioplasty balloons and stents are not approved by the US Food and Drug Administration for use in the cerebral circulation.

Areas of uncertaintyPosterior circulation large vessel occlusion and low NIHSS

Patients with a basilar or vertebral artery occlusion may present with relatively mild symptoms (NIHSS <6), and whether thrombectomy is indicated in these patients remains uncertain. Some proportion of patients who present with initially mild symptoms may have clinical deterioration, but clinical and imaging factors that predict subsequent neurological decline have not yet been defined.

The ATTENTION and BAOCHE trials enrolled patients with NIHSS ≥6 (BAOCHE) and ≥10 (ATTENTION), and there is currently a lack of guidance from prospective and randomized studies to guide the treatment of patients with a posterior circulation LVO and mild symptoms.17 There is a need for future prospective and randomized trials to address these limitations in our knowledge and, at this time, thrombectomy treatment of patients with a vertebral artery occlusion or BAO and NIHSS ≤6 should be based on individual situations that balance the risks and benefits of thrombectomy compared with medical therapy.

Thrombectomy for posterior circulation large vessel occlusion beyond 24 hours

Thrombectomy treatment of patients with BAO was superior to medical therapy in patients treated within 0–12 hours of the last known well (ATTENTION) and 6–24 hours of the last known well (BAOCHE). However, many patients with BAO have a delayed diagnosis due to the non-specific symptoms that are frequently associated with posterior circulation ischemic stroke, and these patients may only be evaluated for possible thrombectomy after >24 hours from the last known well.

There have been isolated case reports of BAO, which have been treated with mechanical thrombectomy after a long duration beyond even 24 hours. Pandhi et al 18 reported their experience treating 10 patients who underwent thrombectomy beyond 24 hours from symptom onset. Successful recanalization (Thrombolysis in Cerebral Infarction 2b–3) was achieved in five patients (50%), which indicates that thrombectomy is feasible and technically successful in this population.19 There are also isolated case reports of BAO patients who underwent thrombectomy >48 hours from the last known well. However, there is tremendous uncertainty as to the benefit of treatment in these extended time windows. Data from the BASICS registry found that functional outcomes were universally poor when recanalization was achieved >9 hours after stroke onset or last known well.20 We agree that there needs to be more clarity to guide thrombectomy treatment of posterior circulation LVO patients >24 hours, and additional studies are needed to address these gaps in our knowledge.

Posterior circulation distal or medium vessel Occlusions

Thrombectomy treatment of patients with occlusion of the P1, P2, or more distal segments of the posterior cerebral artery (posterior circulation distal or medium vessel occlusions) remains unproven. There are anecdotal and retrospective studies that describe the benefits of thrombectomy in these patients, but there are no prospective or randomized data to guide treatment of these patients, which may be reasonable in some circumstances. Future studies are needed to address these gaps in our knowledge.

Updated recommendations

In patients with acute BAO who meet criteria from the BAOCHE or ATTENTION trials (NIHSS score ≥6, PC-ASPECTS ≥6, CTA with BAO, age 18–89 years), thrombectomy is indicated within 12 hours of last known well (class I, Level B-R).

In patients with acute BAO who present between 12 and 24 hours from the last known well, NIHSS score ≥6, or PC-ASPECTS ≥6, thrombectomy is reasonable (class IIa, level B-R).

In patients with acute BAO who present beyond 24 hours from last known well, with NIHSS score ≥6 or PC-ASPECTS≥6, it may be reasonable to consider thrombectomy on a case by case basis (class IIb, level C-EO).

In aged <18 years or >89 years presenting with acute BAO, it is reasonable to consider thrombectomy on a case by case basis (class IIb, level C-EO).

In summary, multiple randomized trials now exist that show a benefit of thrombectomy in populations where there was a lack of data previously. These results justify changes in local patient selection criteria for thrombectomy. Hub and spoke hospital systems should consider incorporating these results in determining which patients are appropriate for transfer to a center capable of performing thrombectomy.

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Acknowledgments

The authors acknowledge Teri Moore and Eddie Woods for logistical support in preparing this document and Justin Fraser for critical review.