We tested the hypothesis that the type of vascular occlusion, recanalisation and collateralisation are predictive of outcome after thrombolytic therapy in acute ischaemic stroke. We carried out angiography and local intra-arterial (97) or systemic (14) thrombolysis within 6 h of the onset in patients with an ischaemic stroke in the territory of the internal carotid artery. Early ischaemic signs (EIS) on pretreatment CT and angiographic findings were classified and analysed in relation to clinical outcome at 3 months. A favourable outcome (Barthel index [BI]>/= 90) was found in 40% of patients with an occlusion of the middle cerebral artery trunk whereas intracranial occlusion of the internal carotid artery ("carotid T occlusion") was followed by death or severe disability (BI<50) in 87%. Significant univariate predictors of favourable outcome were occlusion type ( P<0.01), recanalisation ( P<0.01) and collateralisation ( P<0.01). However, multivariate analysis revealed a significant relationship only between collateralisation and favourable outcome (odds ratio 5.9, 95% confidence interval 1.3-26.7, P=0.02). EIS were not predictive in either case. Occlusion type and recanalisation, are related to outcome only if adequate collateralisation prevents infarction until recanalisation occurs.

A group of 59 patients with stroke due to acute vertebrobasilar or carotid territory occlusion have been treated by local intra-arterial fibrinolysis (LIF). A high recanalisation rate was accomplished with either urokinase or recombinant tissue plasminogen activator (r-TPA). However, with either substance, even if a high dose was used, recanalisation was a time-consuming process which usually took 120 min. A reasonable explanation for the lack of effectiveness of these plasminogen-activating substances might be a deficit of substrate, e.g. plasminogen, in aged thrombus. LIF was capable of improving clinical outcome in acute vertebrobasilar artery occlusion, reducing mortality to 50% in patients fulfilling inclusion criteria. In the carotid territory multiple occlusions had a poor prognosis while good clinical results could be achieved in occlusions of the proximal middle cerebral artery or single branches.

Local intraarterial fibrinolytic therapy (LIF) in patients with acute vertebrobasilar occlusion (AVBO) is a rational and if successful a life saving treatment. The recent progress in this field is determined by the use of microcatheters for superselective basilar artery catheterisation and a "short time, highdose" regimen using 750.000 IU Urokinase in not more than two h. Two out of 7 patients died and 1 did not improve to a better than a locked-in-state. Four patients however survived with excellent outcome.

To improve the efficacy of local intraarterial fibrinolysis (LIF), we compared different fibrinolytic drugs in a cerebral circulation model in the laboratory. The technical efficacy of fibrinolysis, defined as the clot volume lysed per unit time, was found to be optimal with r-tissue plasminogen activator (TPA) activated lys-plasminogen (= plasmin). Subsequently, 20 patients with stroke due to carotid artery territory occlusion were treated by local intraarterial fibrinolysis using the plasmin regimen. The angiographic data and clinical outcome of these patients were compared with those of 40 patients who received plasminogen activators (urokinase or r-TPA) only. Laboratory and clinical data confirmed that plasmin lysis is superior to treatment using only plasminogen activators.

To improve the efficacy of local intraarterial fibrinolysis (LIF), we compared different fibrinolytic drugs in a cerebral circulation model in the laboratory. The technical efficacy of fibrinolysis, defined as the clot volume lysed per unit time, was found to be optimal with r-tissue plasminogen activator (TPA) activated lys-plasminogen (= plasmin). Subsequently, 20 patients with stroke due to carotid artery territory occlusion were treated by local intraarterial fibrinolysis using the plasmin regimen. The angiographic data and clinical outcome of these patients were compared with those of 40 patients who received plasminogen activators (urokinase or r-TPA) only. Laboratory and clinical data confirmed that plasmin lysis is superior to treatment using only plasminogen activators.