Robert W. Regenhardt, MD, PhD
The revolution of acute stroke care, with the 2015 trials demonstrating superiority of endovascular thrombectomy (ET) compared to tPA alone and the subsequent DAWN and DEFUSE 3 trials extending its time window, has raised many questions about which patients will experience net benefit from this powerful therapy. Certainly, some vessel occlusions are more amenable to ET than others, but should the presence of technically difficult occlusions, with perhaps higher procedural risks, limit eligibility? Though poorly represented, patients with anterior circulation tandem lesions, involving both the cervical internal carotid artery (ICA) and an intracranial artery, experienced similar benefits as those with isolated intracranial occlusions in the HERMES meta-analysis. It is unclear if the etiology of tandem lesions predicts outcomes, if etiology should influence the decision to undergo ET, or if it should influence the procedural approach.
The two most common etiologies of tandem lesions are carotid atherosclerosis and carotid dissection. Treatment typically occurs in two phases: management of the cervical ICA lesion by stenting, angioplasty, both, or medical treatment alone, and management of the intracranial occluded vessel by stent retriever or direct aspiration first pass technique. The order of these phases remains controversial, with some centers starting with the intracranial lesion as stent retrievers only require a small microcatheter for deployment. Stenting versus angioplasty of the cervical ICA can be debated based on adequacy of collaterals, risk of reperfusion injury, risk of immediate dual antiplatelet therapy, and other individualized factors.
This study by Gory et al, published in the November 2017 issue of Stroke, sought to compare outcomes of patients with tandem lesions from atherosclerosis and dissection. Prior to this study, the impact of cervical ICA lesion etiology on patient outcomes after ET for tandem occlusions had not been assessed. The TITAN investigators pooled prospectively collected individual data across 18 institutions for all consecutive anterior circulation tandem lesions that were treated with ET, defined by the association of a proximal intracranial occlusion and a cervical ICA lesion (complete occlusion or severe stenosis >90%). They defined etiology by morphology on angiograms: suprabulbar flame-shaped lesions were considered dissection, and calcified bulbar lesions were considered atherosclerosis. If the etiology was unclear, patients were excluded (n=127 unknown ICA etiology, n=10 missing data, n=32 cardioembolic etiology). The primary outcome was favorable outcome at 90 days (mRS 0–2). Secondary outcomes included successful reperfusion (TICI 2b–3), procedure related complications, time to reperfusion, 90-day mortality, and symptomatic intracerebral hemorrhage.
Of the 295 included patients, 65 had ICA dissections and 230 had ICA atherosclerosis. Favorable outcome at 90 days was observed in 56% in the dissection group and 48% in the atherosclerosis group; an NIHSS-adjusted regression model yielded an odds ratio that was not significant. No significant differences were observed in secondary outcomes either. Successful reperfusion occurred in 79% of the dissection group and 75% of the atherosclerosis group. Procedural complications (including new embolic territory, perforation, and dissection) occurred in 14% of the dissection group and 11% of the atherosclerosis group. Median procedural time was 76 min in the dissection group and 67 min in the atherosclerosis group. There were no differences in medical treatment details, including administration of intravenous tPA. However, there were differences in ICA procedural approach where angioplasty alone was more common in the atherosclerosis group (19.2% vs. 5.9%) and no ICA intervention was more common in the dissection group (39.2% vs. 19.2%).
The authors concluded that the etiology of the cervical ICA lesion in tandem lesions may not be an important factor in outcomes or the decision to undergo ET. They noted that their study may have had selection bias given its retrospective design and possible different center-dependent protocols, making it possible that some patients with more challenging lesions were excluded. A previous meta-analysis of tandem lesions was congruent with their outcome rates but did not separate patients by etiology (1). It would be interesting to compare the rates of individual complications (new embolic territory, perforation, etc.) between the lesion etiologies as there may be different implications for patient outcomes not captured in mRS. One might imagine dissections having an increased rate of perforation given pre-procedure damage to the vessel wall and false lumens. However, this type of study would necessitate a large sample size and would likely be difficult to complete.
The lack of differences between etiologies in this study is somewhat surprising, as the underlying physiology of the two is quite different. Dissection is an acute process, similar to cardioembolic stroke, where collaterals may be less likely to form. In contrast, atherosclerosis occurs over time; atherosclerosis-related strokes are more likely associated with better collaterals (2). The authors discuss, therefore, that dissections may be better treated with stents unless good collaterals are observed. Their data do show that there were different procedural approaches between the etiologies. One questions whether the procedural approach may have a more important effect on outcomes than the underlying etiology. However, a recent meta-analysis suggests that there is no difference in the safety and efficacy profiles comparing stenting and angioplasty (3). Future randomized studies are required to further compare both the effects of etiology and approach on these outcomes.
- Sivan-Hoffmann R et al. Stent-Retriever Thrombectomy for Acute Anterior Ischemic Stroke with Tandem Occlusion: A Systematic Review and Meta-Analysis. Eur Radiol. 2017 Jan;27(1):247-254.
- Rebello LC et al. Stroke etiology and collaterals: atheroembolic strokes have greater collateral recruitment than cardioembolic strokes. Eur J Neurol. 2017 Jun;24(6):762-767.
- Wilson MP et al. Management of tandem occlusions in acute ischemic stroke – intracranial versus extracranial first and extracranial stenting versus angioplasty alone: a systematic review and meta-analysis. J Neurointerv Surg. 2018 Mar 9.