Can the time window for administration of thrombolytics in stroke be increased?

Level 1 evidence now shows that thrombolysis in cases of acute ischaemic stroke is effective if administered within 3 hours of stroke onset. This benefit has been shown to be time dependent and potentially extends beyond 3 hours, with evidence that potentially viable penumbral tissue may be present in a significant proportion of cases well beyond 3-6 hours and, in isolated cases, perhaps up to 48 hours. This exposes a "stroke recovery gap", the difference observed between the clinical response to thrombolytic therapy in a given population of patients presenting with ischaemic stroke and the potential clinical recovery if all of the penumbra were salvaged under ideal circumstances. The means of bridging this "stroke recovery gap" using thrombolysis must involve extending the therapeutic time window (i.e. the time between stroke onset and administration of thrombolytics). Approaches to do this include the use of: (i) improved patient selection with modern neuroimaging techniques, particularly magnetic resonance imaging using perfusion-weighted image/diffusion-weighted image mismatch; (ii) newer thrombolytic agents; (iii) lower doses of these agents; (iv) varied methods of administration of thrombolytic therapy including combined intravenous and intra-arterial approaches; and (v) adjunctive therapies such as neuroprotectants. Should these means of extending the time window for thrombolysis prove successful, a more widespread use of this form of acute stroke therapy will be possible.