Three neutral RCTs in a row. A field at a crossroads. Elisa Francesca Ciceri and Jan Gralla cut straight to what matters, from defining MeVO to what actually happens in the room when a distal clot shows up on the screen.
Defining MeVO remains a moving target, with no universally agreed boundary. Should the field adopt a strict anatomical consensus, or does clinical context (NIHSS, collaterals, territory at risk) matter more in your day-to-day decision-making?
Elisa Francesca Ciceri: This tension is very real, and in practice most of us already operate somewhere between those two poles. A purely anatomical definition of MeVO (for example M2–M3, A2–A4, P2–P3, cerebellar branches) has a clear advantage in simplifying communication. Indeed, without a shared anatomical language, MeVO risks becoming an abbreviation for “anything smaller than an ICA,” which compromises comparability between studies and centers. That said, everyday clinical decision-making is rarely based solely on anatomy. In real practice, it is very important to consider anatomy as a starting point, but not as the endpoint of the decision. In fact, functional eloquence matters more than diameter. An occluded M3 supplying the dominant language cortex or a P2 calcarine branch threatening vision can be far more disabling than a proximal non-dominant M2. Additionally, it is a fact that the NIHSS underestimates distal eloquent strokes. Therefore, the presence of collateral circulation and the state of cerebral perfusion become crucial when considering the risk-benefit equation of treatment. A small distal clot with poor collaterals but a large threatened territory is biologically crucial, regardless of the name of the vessel. Therefore, rather than choosing between anatomy or clinical context, today we need a definition that encompasses both: a rigorous anatomical definition of MeVO, in order to reach a scientific consensus and avoid ambiguity, along with a clinical framework sensitive to context to consider therapeutic decisions in the real world. In summary, anatomy is necessary but insufficient; the clinical context, eloquence, collaterals, and tissue at risk often matter more than the name of the vessel. Most experienced practitioners already operate in this way—what is missing is our formal language, which must find a way to align with it.
Jan Gralla: In light of the negative results of the three randomized controlled trials, our current day-to-day decision-making remains multifactorial. It particularly considers the location of the occlusion, which affects both the likelihood of successful recanalization and the risk of complications. However, it must also take into account the patient’s clinical symptoms (NIHSS) and, whenever possible, MRI-based mismatch imaging to estimate the amount of salvageable tissue. In the long term, I assume that a consensus will emerge regarding a threshold defining how far distally mechanical thrombectomy should be pursued and from which point onward other approaches, such as thrombolytics, may play a more important role in limiting the risks associated with mechanical thrombectomy. From my point of view, there is a high likelihood that this threshold will differ between vascular territories. For example, mechanical thrombectomy in M3/M4 branches of the MCA inferior trunk appears to be safer and more successful than interventions at the same level within the superior trunk territory.
Were you genuinely surprised by the neutral results of ESCAPE-MeVO, DISTAL, and the DISCOUNT interim analysis presented at ISC 2025, or did you see signals in earlier data that tempered your optimism?
E.C: When ISC 2025 arrived, there were already enough warning signs that had tempered the initial enthusiasm regarding MeVO thrombectomy. Registries and meta-analyses consistently confirmed the technical success in MeVO, but with modest and inconsistent clinical effects, especially when considering the initial NIHSS and the infarct volume. This should already have raised concerns that a broad “MeVO for all” strategy could undermine the benefit. ESCAPE-MeVO and DISTAL pragmatically embraced inclusivity, but that also meant enrolling many patients with little room for measurable improvement. Finally, DISCOUNT confirmed what many operators already suspected: patient selection is everything in MeVO. What slightly surprised me was how consistently neutral the results were across studies using different healthcare systems and workflows. This suggests that it is not just a matter of execution or device, but a conceptual issue of selection. I do not see these studies as the end of MeVO thrombectomy. Personally, considering future developments, I do not believe that the neutral results obtained so far have invalidated the concept of MeVO treatment itself. They are valuable because they have highlighted the fact that MeVOs should not be treated like small LVOs with the same logic and study design. Therefore, these results have the enormous advantage of guiding us towards alternative approaches, whether medical or procedural.
J.G: Two major messages arise from the negative RCTs published recently. First, our current mechanical approaches, largely derived from experience with LVO treatment, do not demonstrate the same clinical effectiveness in more distal territories, at least in the overall study population of these trials. This is not particularly surprising, as the clinical symptoms are often less severe, the territory at risk becomes smaller, and the vessels more fragile and tortuous. Previous observational studies had already suggested this mismatch in effectiveness (e.g. DUSK study, Stroke 2024). Second, and most importantly, even under best medical treatment, outcomes in distal vessel occlusions remain poor. In other words, there is still substantial room for improvement, and distal vessel occlusion remains an unresolved clinical problem. I think we were facing a similar situation in 2012, when the randomized controlled trials in large vessel occlusions, utilizing various heterogeneous and relatively immature local treatment approaches, initially yielded negative results.
I believe there is a high likelihood that positive evidence for mechanical thrombectomy in distal vessel occlusions will emerge within the next five years, particularly as device technology continue to improve.
Post hoc analyses point to potential subgroups (dominant M2, high NIHSS). What is your current practical approach: do you still offer thrombectomy to selected MeVO patients outside trials, and if so, on what criteria?
E.C: I am more willing to treat dominant or clearly eloquent M2 occlusions, select proximal P2 and A2 occlusions only if the eloquence is clear, rarely distal M3/P3 cases, only when the territory is functionally relevant and the vessel is technically favorable. I am much less inclined to treat very distal and tortuous branches, distal multifocal emboli with unclear relevance. If the vessel appears difficult to navigate and the procedure presents a high risk, the margin of benefit may be too low to justify an aggressive intervention. Before prescribing the intervention, I carefully review neuroimaging to assess mismatch and tissue at risk, collateral circulation, eloquent territory, and the extent of consolidated core on NCCT or DWI. A perfect TICI score will not matter if there is no significant brain to save! Finally, the human factor is relevant to me in order to achieve the best collaboration: being very clear with the patient and the family that MeVO thrombectomy is not yet a “standard of care” procedure, and must be considered only in specific cases, with an outcome still uncertain.
J.G: In daily clinical decision-making, there is a substantial difference between M2 occlusions and more distal vessel occlusions. M2 has always been a familiar target and landing zone for e.g. stent retrievers during mechanical thrombectomy for large vessel occlusions. Given the size of the affected territory, the well-known, rather uncomplicated vascular anatomy, I still consider these occlusion sites to be appropriate indications for mechanical thrombectomy, particularly when the clinical deficit is functionally disabling. A similar clinical situation may occur in severely affected patients (high NIHSS) with an occlusion pattern that offers relatively easy access and a low complication risk, such as proximal M3 occlusions of the inferior MCA trunk or pericallosal artery occlusions.
The distal vasculature presents unique challenges (tortuosity, caliber, perforation risk). How has your technique evolved, and what device profile (aspiration, stent retriever, or combined) do you currently favor?
E.C: My MEVO technique has evolved quite substantially in recent years, mainly driven by a sober reassessment of risk tolerance in a vascular territory with very little margin for error. Distal vessels do not forgive imprecision, and neutral results in MeVO studies have reinforced that procedural safety is more important than ever. In my practice, I try to achieve a single "first pass" attempt with minimal vessel manipulation, avoiding acrobatic maneuvers, aiming to maintain a very low complication rate. I dedicate more time to positioning the support catheter (distal ICA or proximal M1) to avoid repeated crossings. My dominant strategy is based on aspiration-first, but I consider a stent retriever when the clot is clearly organized and focal, and the vessel is relatively straight. I always remind myself that distal vasculature rewards humility. Seems to be trivial, but the botton line is that our techniques must provide a clinical advantage rather than achieve a perfect angiographic result!
J.G: From my point of view, the main driver is the tortuosity of the vessels in the distal territory, generally within a specific vascular territory and on an individual patient basis. This is associated with an increased risk of perforation and shearing of perforating arteries when the vessel is straightened during the application of mechanical forces, as well as with a decreased likelihood of successful recanalization. To limit the local application of mechanical forces during thrombectomy, several techniques are emerging, such as aspiration-based approaches using continuous aspiration and, especially cyclic aspiration techniques. Other promising strategies include the use of stent retrievers with adjustable radial force during retrieval, such as the Tigertriever 13, as investigated in the DISTALS trial, as well as the application of local intra-arterial thrombolytic agents. In my current practice today, I generally favor aspiration-first or small diameter stent-retriever in combination with local aspiration.
