Review and highlight the literature from the early twentieth century in AIS management.

We performed a PubMed search regarding thrombolysis in cerebral arterial occlusions between 1900 and 1980.

Sixteen articles met the inclusion criteria for revision. Streptokinase (SK) in 1933 and urokinase (uPA) in 1947 were the first fibrinolytics used in AIS. In 1955, Tillett reported a case series (n=11) with the potential SK side effects. Fletcher evaluated uPA infusion (n=31) in AIS patients and found no therapeutic benefits in 1975. Furthermore, earlier studies using SK or uPA demonstrated increased intracranial hemorrhage (ICH) rates. In 1958, Sussman suggested using TT in cerebral artery occlusions under cerebral angiography using fibrinolysin, a bovine plasma enzyme derived. Three patients recanalized the middle cerebral artery (MCA), and one patient had clinical benefit. Meyer conducted the first double-blinded clinical trial in 1963. The study evaluated carotid and MCA occlusions (n=40). He administered intravenous plasmin or placebo daily for 72 hours. There were no differences between the two groups. Another trial in 1964 revealed that SK and heparin's combination caused higher mortality and ICH rates than heparin alone in 73 stroke patients. Importantly, CT became available in the mid-1970s; therefore, ICHs could have been present before the drug administration.

The use of TT in AIS has had significant progress in the last 70 years. The failed studies were the anteroom for fibrinolytic therapy's development with a better risk-benefit profile such as Alteplase or Tenecteplase.