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More advanced computed tomography and magnetic resonance imaging studies are available that can be used to identify a small ischemic core and ischemic penumbra, and this information will contribute increasingly in treatment decisions as the therapeutic time window is lengthened. Intravenous thrombolysis with tissue-type plasminogen activator remains the mainstay of acute stroke therapy within the initial 4.5 hours after stroke onset, despite the lack of Food and Drug Administration approval in the 3- to 4.5-hour time window. In patients with proximal, large-vessel occlusions, IA device-based treatment should be initiated in patients with small\/moderate-sized ischemic cores who can be treated within 6 hours of stroke onset. The organization and implementation of regional stroke care systems will be needed to treat as many eligible patients as expeditiously as possible. Novel treatment paradigms can be envisioned combining neuroprotection with IA device treatment to potentially increase the number of patients who can be treated despite long transport times and to ameliorate the consequences of reperfusion injury. 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