Fast Versus Slow Progressors of Infarct Growth in Large Vessel Occlusion Stroke: Clinical and Research Implications

Approximately 40% of acute ischemic strokes are caused by proximal intracranial large vessel occlusion (LVO) and are associated with the worst clinical outcomes.1 Early reperfusion with IV tPA (tissue-type plasminogen activator) and intra-arterial thrombectomy leads to reduced final infarct volumes, lower disability rates, and improved cognitive function after anterior circulation LVO.2–6 However, most stroke patients with LVO remain untreated because they present beyond the conventional time windows for acute reperfusion therapies.7,8 Therefore, a growing paradigm has been to transition to a therapeutic window that is tailored to each patient’s individual pathophysiology or brain tissue window rather than a standardized time window.9,10 The principle of pathophysiology-based reperfusion therapy is built on the fundamental concept of a dynamic interrelation between the ischemic core (tissue that is already infarcted) and the ischemic penumbra (physiologically impaired but potentially salvageable tissue).11–13 After arterial occlusion, there can be temporal growth of the ischemic core into the penumbral area that is modulated by collateral blood flow, the key element setting the pace of the ischemic process.14 Infarct growth is thought to progress at different speeds across individuals because patients with occlusion of the proximal middle cerebral artery (MCA) or internal carotid artery (ICA) terminus present with widely variable stroke volumes independently of time after symptom onset.15–18 We refer to patients with LVO who experience rapid infarct growth as fast progressors. These patients have failing collaterals and a large ischemic core despite presenting early within 6 hours of stroke onset. Conversely, a significant number of patients maintain a small ischemic core and significant salvageable tissue beyond 6 hours and up to several days after persistent LVO.17,19 The latter patients are slow progressors because they maintain good collaterals and …