Timing of Recanalization and Functional Recovery in Acute Ischemic Stroke

Abstract

Background and purpose: Although onset-to-treatment time is associated with early clinical recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (tPA), the effect of the timing of tPA-induced recanalization on functional outcomes remains debatable.

Methods: We conducted a multicenter, prospective observational cohort study to determine whether early (within 1-hour from tPA-bolus) complete or partial recanalization assessed during 2-hour real-time transcranial Doppler monitoring is associated with improved outcomes in patients with proximal occlusions. Outcome events included dramatic clinical recovery (DCR) within 2 and 24-hours from tPA-bolus, 3-month mortality, favorable functional outcome (FFO) and functional independence (FI) defined as modified Rankin Scale (mRS) scores of 0-1 and 0-2 respectively.

Results: We enrolled 480 AIS patients (mean age 66±15 years, 60% men, baseline National Institutes of Health Stroke Scale score 15). Patients with early recanalization (53%) had significantly (P<0.001) higher rates of DCR at 2-hour (54% vs. 10%) and 24-hour (63% vs. 22%), 3-month FFO (67% vs. 28%) and FI (81% vs. 39%). Three-month mortality rates (6% vs. 17%) and distribution of 3-month mRS scores were significantly lower in the early recanalization group. After adjusting for potential confounders, early recanalization was independently associated with higher odds of 3-month FFO (odds ratio [OR], 6.19; 95% confidence interval [CI], 3.88 to 9.88) and lower likelihood of 3-month mortality (OR, 0.34; 95% CI, 0.17 to 0.67). Onset to treatment time correlated to the elapsed time between tPA-bolus and recanalization (unstandardized linear regression coefficient, 0.13; 95% CI, 0.06 to 0.19).

Conclusions: Earlier tPA treatment after stroke onset is associated with faster tPA-induced recanalization. Earlier onset-to-recanalization time.

Results: in improved functional recovery and survival in AIS patients with proximal intracranial occlusions.

Keywords: Outcomes; Reperfusion; Stroke; Thrombolysis.

Figure 1.

Frequency of favorable functional outcome by elapsed time between symptom onset and the beginning of recanalization, as predicted by unadjusted analysis in patients with sustained complete or partial recanalization at the end of transcranial Doppler-monitoring (n=301). The recanalization cohort (including patients with complete or partial sustained recanalization) was divided into groups of about 30 on the basis of deciles in the time to recanalization. The red circles show the proportion with favorable functional outcome and mean time to recanalization in each group, and the red horizontal lines depict the range of time included in that group. The solid curve shows the model results from the logistic regression analysis, with 95% confidence interval prediction bands shown in dashed curves. Favorable functional outcome was defined as a modified Rankin Scale score of ≤1.

Figure 2.

Correlation of elapsed time between symptom onset and tissue plasminogen activator (tPA)-bolus (onset to treatment time) with elapsed time between tPA-bolus to the beginning of recanalization in patients with sustained complete or partial recanalization at the end of transcranial Doppler-monitoring (n=301). The 95% confidence interval (CI) forecast bands are also presented. The correlation between the two time intervals was statistically significant (unstandardized linear regression coefficient, 0.13; 95% CI, 0.06 to 0.19; P<0.001).