Mustafa and colleagues^{Reference Mustafa, Panigrahi and Haldar1} present a thoughtful systematic review and meta-analysis on endovascular treatment (EVT) for acute ischemic stroke due to medium vessel occlusion (MeVO) that summarizes the currently available randomized evidence. Many questions with regard to MeVO EVT still remain unanswered, and the review provides a solid starting point to formulate these questions and direct future research in this rapidly evolving field, where uncertainty still dominates clinical decision-making.

Their meta-analysis shows that EVT for acute stroke due to MeVO did not provide additional benefit over best medical treatment (BMT). Proportions of excellent functional outcome (mRS 0–1) and functional independence (mRS 0–2) at 90 days were similar in MeVO patients treated with EVT versus BMT, while symptomatic intracranial hemorrhage (5.7% vs 2.4%, RR: 2.39 [95% CI: 1.26–4.53]) and serious adverse events (38.2% vs 28.9%, RR: 1.32 [95% CI: 1.11–1.56]) were more common in the EVT group. Mortality at 90 days was numerically, albeit not significantly, higher in the EVT group (14.4% vs 11.2%, RR: 1.29 [95% CI: 0.94–1.76]). These findings, consistent across the included trials, underscore the technical and clinical challenges of extending EVT beyond large vessel occlusion (LVO).

Selection bias is often cited as a possible explanation for these neutral results and may have compromised external trial validity; however, there are no obvious major methodological flaws to suggest compromised internal trial validity. ^{Reference Goyal and Ganesh4} In other words, the trial results, although perhaps not applicable to the entirety of MeVO stroke patients, are still true to the population included in the trials (internal validity), and in the included patient population, EVT clearly did not improve outcomes. Several additional factors may have contributed. ^{Reference Stebner, Bosshart and Fujiwara5,Reference Pensato, Demchuk and Menon6} First, devices currently in use were developed primarily for LVOs and may be suboptimal for the smaller, tortuous anatomy of MeVOs – although new generations are under development. Second, patient selection remains central: imaging characteristics, collateral status and baseline National Institutes of Health Stroke Scale (NIHSS) thresholds may all influence EVT benefit, and the thresholds used in the MeVO EVT trials (mostly adapted from LVO trials) may not have been optimal to identify MeVO patients with potential to benefit from EVT. Third, time is particularly crucial in MeVO, where workflow delays seem to have a detrimental impact, reinforcing the need for faster imaging-to-reperfusion pathways.

Mustafa et al. set the stage for future randomized trials with refined patient selection, optimized workflow efficiency and EVT strategies specifically designed for MeVO. Until such data are available, equipoise remains, and careful case-by-case judgment is required in clinical practice.