From Recanalization to Failed Recovery: No Reflow, No Rescue, and No Regrow After Thrombectomy.

Despite the remarkable technical success of endovascular thrombectomy (EVT) in achieving high recanalization rates for acute ischemic stroke due to large vessel occlusion (LVO), angiographic success does not consistently translate into functional recovery. Approximately 50% of successfully recanalized patients failed to achieve functional independence at 90 days, a phenomenon termed futile recanalization (FR). Futile recanalization highlights the biological limitations of macrovascular reperfusion alone. We propose a mechanistic framework for FR centered on the "3 R's" of stroke recovery: No-Reflow, No-Rescue, and No-Regrow. No-Reflow refers to microvascular failure despite proximal recanalization, driven by capillary obstruction, endothelial injury, pericyte constriction, and thromboinflammatory processes. No-Rescue describes secondary loss of initially salvageable neurons due to complement activation, neuroinflammation, oxidative stress, and blood-brain barrier dysfunction. No-Regrow reflects impaired neuroplasticity in the subacute and chronic phases, including failed neurogenesis, axonal degeneration, white matter injury, and disrupted network reorganization. This review examines the clinical, imaging, procedural, and molecular determinants of FR to better understand why successful reperfusion does not always result in neurological recovery. Understanding the multifactorial nature of FR is essential to improving EVT outcomes. Future strategies should target microvascular injury and inflammation, refine patient selection criteria, and explore adjunctive therapies aimed at restoring downstream perfusion and mitigating neuroinflammation. By addressing both macrovascular and microvascular factors, it may be possible to translate angiographic success into meaningful functional recovery.