• Georgios Tsivgoulis, Apostolos Safouris, and Andrei V Alexandrov.
• The University of Tennessee Health Science Center, Department of Neurology , 855 Monroe Avenue, Suite 415, Memphis, TN 38163 , USA +1 901 448 6199 ; +1 901 448 7440 ; avalexandrov@att.net.
• Expert Opin Drug Saf. 2015 Jun 1; 14 (6): 845-64.

IntroductionIntravenous administration of tissue-type plasminogen activator (IV-tPA) remains the only approved therapy that may reverse neurological deficit in patients with acute ischemic stroke (AIS). During the past 20 years, accumulating real-word experience have provided additional information regarding its safety and efficacy in various clinical settings that were originally considered as contraindications for systemic thrombolysis.Areas CoveredIn this narrative review, we address the safety of intravenous thrombolysis (IVT) in specific conditions: dissection of the aortic arch of extracranial and intracranial arteries, concomitant presence of unruptured intracranial aneurysms, arteriovenous malformations and dural fistulas, co-existing brain tumors as well as in conditions mimicking AIS. The review systematically evaluates the safety of off-label use of IVT and summarizes data from case reports of uncommon complications of systemic thrombolysis administration in the setting of acute cerebral ischemia.Expert OpinionThe present narrative review summarizing 20 years of clinical experience with IVT for AIS highlights that many of the current guidelines and protocols should be adjusted to accommodate recent data from registries and real-world experience underscoring the safety of IVT in numerous conditions of AIS that were originally considered as relative or absolute contraindications for administration of IV-tPA.

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