Investigating Neurologic Improvement After IV Thrombolysis

Background and objectives: Time from stroke onset is associated with clinical response to intravenous thrombolysis with alteplase (IVT) and is therefore used to select patients for treatment. Alternatively, neuroimaging may be used for treatment in the uncertain or extended time window. We hypothesized that the patient-specific imaging indicator of ischemic lesion progression ("tissue clock") using CT-perfusion (CTP) or quantitative net water uptake (NWU) is a predictor of early neurological improvement (ENI) independent of time.

Methods: Observational study of anterior circulation ischemic stroke patients with proximal vessel occlusion and known time from symptom onset triaged by multimodal-CT undergoing endovascular treatment. Quantitative NWU using an established threshold (11.5%) or CTP lesion-core mismatch (EXTEND criteria) were used to estimate ischemic lesion progression. The treatment effect of IVT depending on lesion progression defined by tissue clock versus time clock was assessed by inverse-probability weighting (IPW). Endpoints were binarized ENI and functional independence at day-90.

Results: 409 patients were included, of which 223 (54.5%) received IVT. The proportion of patients within an early time window (<4.5h), low NWU, and CTP-mismatch were 45.0%/86.5%/80.3%. In IPW, IVT was associated with higher rates of ENI (%-difference: 7.3%,p=0.02). For patients with CTP-mismatch or low NWU, IVT was associated with a 9.6%/7.2% higher rate of ENI, which was different than the effect of IVT in patients without CTP-mismatch or high NWU (-9.3%/-7.3%; p=0.004/p=0.03), while early treatment window did not modifiy the effect of IVT.

Discussion: CT-based measures of the "tissue clock" might identify patients who benefit from IVT more accurately than conventional time windows. Considering the high number of patients with early "tissue clock" (low NWU/CTP-mismatch) within an extended time window, considerable benefit from IVT using imaging indicators of the "tissue clock" may be achieved.