Pharmacological and Non-Pharmacological Recanalization Strategies in Acute Ischemic Stroke

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Abstract
According to the guidelines of the European Stroke Organization (ESO) and the American Stroke Association (ASA), acute stroke patients should be managed at stroke units that include well organized pre- and in-hospital care. In ischemic stroke the restoration of blood flow has to occur within a limited time window that is accomplished by fibrinolytic therapy. Newer generation thrombolytic agents (alteplase, pro-urokinase, reteplase, tenecteplase, desmoteplase) have shorter half-life and are more fibrin-specific. Only alteplase has Food and Drug Administration (FDA) approval for the treatment of acute stroke (1996). The National Institute of Neurological Disorders and Stroke (NINDS) trial proved that alteplase was effective in all subtypes of ischemic strokes within the first 3 h. In the European cooperative acute stroke study III trial, intravenous (IV) alteplase therapy was found to be safe and effective (with some restrictions) if applied within the first 3–4.5 h. In middle cerebral artery (MCA) occlusion additional transcranial Doppler insonication may improve the breakdown of the blood clot. According to the ESO and ASA guidelines, intra-arterial (IA) thrombolysis is an option for recanalization within 6 h of MCA occlusion. Further trials on the IA therapy are needed, as previous studies have involved relatively small number of patients (compared to IV trials) and the optimal IA dose of alteplase has not been determined (20–30 mg is used most commonly in 2 h). Patients undergoing combined (IV + IA) thrombolysis had significantly better outcome than the placebo group or the IV therapy alone in the NINDS trial (Interventional Management of Stroke trials). If thrombolysis fails or it is contraindicated, mechanical devices [e.g., mechanical embolus removal in cerebral ischemia (MERCI)- approved in 2004] might be used to remove the occluding clot. Stenting can also be an option in case of acute internal carotid artery occlusion in the future. An intra-aortic balloon was used to increase the collateral blood flow in the Safety and Efficacy of NeuroFlo™ Technology in Ischemic Stroke trial (results are under evaluation). Currently, there is no approved effective neuroprotective drug.

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