Abstract 3290: Timing Of Recanalization After Intravenous Thrombolysis Determines The Functional Outcomes In Acute Ischemic Stroke

Abstract

Background and Purpose: Intravenously administered tissue plasminogen activator (IV-TPA) is the only approved therapeutic agent for arterial recanalization in acute ischemic stroke (AIS). Wide variations in rates and timing of neurological recovery are observed in thrombolyzed patients. Although, recanalization of acutely occluded intracranial artery remains the major aim IV-TPA, timing and impact of this phenomenon on functional outcomes has not been evaluated properly. We evaluated the relationship between the arterial patency and timing of recanalization with functional outcomes at 3-months in AIS. Methods: Data for consecutive AIS patients treated with IV-TPA within 4.5 hours of symptom-onset during 2007-2010 were prospectively entered in the thrombolysis registry maintained at our tertiary care center. Data were collected for demographic characteristics, vascular risk factors, stroke subtypes and blood pressure before IV-TPA bolus. National Institute of Health Stroke Scale (NIHSS) scores were obtained before IV-TPA, at 2-hours and at 24-hours. Patients were continuously monitored with 2-MHz pulsed wave diagnostic transcranial Doppler (TCD) for 2-hours after IV-TPA bolus for early recanalization (ER). ER was assessed using the Thrombolysis in Brain Ischemia grading TCD system. Arterial patency was assessed on day 2 in patients who underwent CT angiography or magnetic resonance angiography, labeled as delayed recanalization (DR). Absence of recanalization on early TCD or imaging on day 2 was called persistent arterial occlusion (PAO). Favorable functional outcomes at 3 months were determined by modified Rankin scale (mRS) of 0-1. Results: Of the 2238 AIS patients admitted during the study period, 240 (11%) received IV-TPA within 4.5-hours of symptom-onset. Median age was 65yrs (range 19-92), 63% males, median NIHSS 17points (range 3-35) and median onset-to-treatment time 149 minutes. Overall, 122 (50.8%) patients achieved favorable functional outcome at 3-months. Information about ER, DR and PAO was available for 160 patients- ER in 55(34.4%), DR in 44(27.5%) and PAO in 61(38.1%) patients. Timing of recanalization was associated with favorable outcome (ER 72.7%, DR 63.6% and PAO 31.1%; p<0.005). Factors associated with favorable outcome at 3-months on univariable analysis were younger age, female gender, atrial fibrillation, baseline NIHSS, onset-to-treatment time and timing of recanalization. However, on multivariable analysis, NIHSS at onset (OR per 1-point increase 0.907, 95%CI 0.848-0.969), ER (OR 3.32, 95%CI 1.295-9.474) and DR (OR 3.021 95%CI 1.197-7.634) were found as independent predictors of favorable outcome at 3-months. Conclusions: Timing of arterial recanalization induced by IV-TPA in acute ischemic stroke is a strong predictor of favorable outcome at 3-months.