OPEN TRIAL OF INTRAVENOUS TISSUE-PLASMINOGEN ACTIVATOR IN ACUTE CAROTID TERRITORY STROKE - CORRELATIONS OF OUTCOME WITH CLINICAL AND RADIOLOGICAL DATA

Background and Purpose Pilot studies using early thrombolytic therapy in stroke have suggested that recombinant tissue plasminogen activator (rTPA) might be effective. While large, double-blind, randomized stud ies are needed, open trials could generate hypotheses concerning (1) t he clinical correlations of outcome, (2) the significance of CT scan d ata during the first week, and (3) the use of adjunctive therapies. Me thods We performed an open trial of intravenous rTPA on patients refer red to our emergency service with all types of ischemic stroke in the carotid territory. All patients between 20 and 81 years hospitalized d uring 1994 with completed stroke in the internal carotid artery territ ory and a baseline Scandinavian Stroke Scale score lower than 48, even with severe disturbances of consciousness, were included. The inclusi on time was within 7 hours after stroke onset. A 0.8-mg/kg dose of rTP A was infused fur 90 minutes. Intravenous heparin was given either imm ediately at efficient dosage or after 24 hours. Mannitol was used in p atients with severe presentation. The Scandinavian Stroke Scale evalua tion was done at baseline, 3 hours, and 1, 7, 30, and 90 days. The CT scan was performed before the treatment and at days 1 (24 +/- 6 hours) and 7. Results Forty-three consecutive patients met the criteria of t he protocol. The mean age at inclusion was 65 +/- 10.4 years, and the mean interval to treatment was 232 +/- 79 minutes. At day 90, 25 patie nts (58.1%) exhibited a complete regression of symptoms, and 3 had mod erate neurological sequelae. Thirteen patients had severe neurological sequelae, 11 with infarcts and 2 with secondary parenchymal hematomas . Two patients died (4.6%), 1 with hematoma. The overall hematoma rate was 6.9%. Excellent outcome at day 90 was significantly correlated wi th major neurological improvement at day 1. Intravenous immediate hepa rin versus delayed heparin after 24 hours improved the ischemic outcom e but not the overall outcome. Reinfarction syndromes after major neur ological improvement, likely to be rethrombosis syndromes, were observ ed in 3 patients (6.9%). For the day 1 CT scan. poor outcome was assoc iated with the presence of structured and homogeneous hypodensities li kely to represent classic infarcts, as confirmed by day 7 CT scan. Con versely, total recovery was significantly associated with the absence of any image or with unstructured hypodensities, a particular type of image characterized by its heterogeneous darkness and often polylobar shape. This type of image disappeared at day 7 in 17.6% of the cases a nd is likely to represent reperfusion images and/or incomplete ischemi c damage. Conclusions The results obtained in this open, small study s uggest safety and effectiveness of rTPA thrombolysis at the dose of 0. 8 mg/kg within 7 hours in acute strokes of the carotid territory, incl uding highly serious baseline neurological presentations, until age 81 years and under special therapeutic conditions. Complete recovery is significantly associated with major neurological improvement during th e first 24 hours and the presence of a particular type of image at day 1 CT scan characterized by an unstructured hypodensity, often polylob ar and heterogeneous, which is likely to correspond to reperfusion ima ges.