Large cerebral artery occlusion and recanalisation in stroke patients treated with intravenous thrombolysis : clinical and radiological markers and their clinical relevance

Sammanfattning: Large cerebral artery occlusion accounts for 40-46% of ischemic strokes. These strokes are characterized by extensive neurological deficit, poor functional outcome, and increased mortality (up to 40-80% in the most severe clinical syndromes). Intravenous thrombolysis is approved treatment across severity grades, except for the extremely severe, although alternative strategies are under evaluation, such as mechanical thrombectomy. The aim of the present thesis was to study the occurrence and impact of recanalisation in a large cohort of ischemic stroke patients with documented large cerebral artery occlusion treated with intravenous thrombolysis. Data were collected through the internet-based Safe Implementation of Treatment of Stroke - International Stroke Thrombolysis Register (SITS-ISTR). Study I We explored baseline factors associated with middle cerebral artery occlusion, as determined by presence of hyperdense middle cerebral artery sign (HMCAS) on admission CT scan, and its relation to functional outcome and symptomatic intracranial hemorrhage in stroke patients treated with intravenous thrombolysis. HMCAS patients (n=1905, 19% of the whole study population) were younger, but had severer stroke at baseline and less favorable outcomes at 3 months compared to non-HMCAS patients. Intravenous thrombolysis treatment in patients with HMCAS on admission CT scans did not increase the rate of symptomatic intracranial hemorrhage after treatment, though asymptomatic hemorrhagic transformation was increased. We conclude that the presence of HMCAS on baseline CT is not a reason to exclude patients from treatment with intravenous thrombolysis. Study II We analysed the association of HMCAS disappearance after intravenous thrombolysis, which implies vessel recanalisation, with early neurological improvement, stroke functional outcome, and symptomatic intracranial hemorrhage, and attempted to find predictors of HMCAS disappearance from baseline. The admission HMCAS disappears on 22–36h CT scans after intravenous thrombolysis in almost half of all cases (n=831). The proportion of functionally independent patients in the HMCAS disappearance subgroup was more than double (42% vs. 19%) and mortality was less than half (15% vs. 30%) compared with the HMCAS persistence subgroup. A higher prevalence of infarct-related parenchymal haemorrhage in the HMCAS disappearance subgroup did not influence overall favorable 3 month outcome. The prognosis in patients with MCA occlusion that persists after intravenous thrombolysis is poor; this finding strengthens the appeal for alternative treatment approaches in this subgroup. Study III We examined the impact of early neurological improvement, defined in various ways according to the previous literature, on functional outcome in patients with large vessel occlusion on admission CT- or MR angiography (n=798), and its ability to predict vessel recanalisation. Early neurological improvement at 2h and 24h was associated with vessel recanalisation at 22-36h but also with functional independence at 3 months. Early neurological improvement by 20% at 2h was the best predictor of 3 months functional outcome and recanalisation after thrombolysis. Fairly accurate, it may serve as a surrogate marker of recanalisation, if imaging evaluation of vessel status is not available. If recanalisation status is required after intravenous thrombolysis, vascular imaging is recommended despite neurological improvement. Study IV We investigated the importance of recanalisation status in stroke patients (n=5324) with and without early neurological improvement after intravenous rtPA. Recanalisation of an occluded artery in acute stroke was associated with favorable functional outcome both in patients with and without neurological improvement after intravenous thrombolysis. Combination of vessel recanalisation and early neurological improvement was by far the most favorable clinical scenario. In future evaluations of mechanical thrombectomy and other additional strategies, recanalisation strategy should be considered in patients with persisting occlusion after intravenous thrombolysis even in case of significant neurological improvement. In summary, the present thesis demonstrates satisfactory effect of intravenous thrombolysis in approximately half of the patients with large cerebral artery occlusion, and poor prognosis for those who are lacking early treatment response. Our findings support the search of alternative treatment approaches aimed to achieve vessel recanalisation for the latter group, based on early objective evaluation of vessel status.