Adjunct Thrombolysis Enhances Brain Reperfusion following Successful Thrombectomy

Abstract

Objective: This study was undertaken to investigate whether adjunct alteplase improves brain reperfusion following successful thrombectomy. Methods: This single-center, randomized, double-blind, placebo-controlled study included 36 patients (mean [standard deviation] = 70.8 [13.5] years old, 18 [50%] women) with large vessel occlusion undergoing thrombectomy resulting in near-normal (expanded Thrombolysis in Cerebral Infarction [eTICI] b50/67/2c, n = 23, 64%) or normal angiographic reperfusion (eTICI 3, n = 13, 36%). Seventeen patients were randomized to intra-arterial alteplase (0.225mg/kg), and 19 received placebo. At 48 hours, patients had brain perfusion/diffusion-weighted magnetic resonance imaging (MRI) and MRI-spectroscopy. The primary outcome was the difference in the proportion of patients with areas of hypoperfusion on MRI. Secondary outcomes were the infarct expansion ratio (final to initial infarction volume), and the N-acetylaspartate (NAA) peak relative to total creatine as a marker of neuronal integrity. Results: The prevalence of hypoperfusion was 24% with intra-arterial alteplase, and 58% with placebo (adjusted odds ratio = 0.20, 95% confidence interval [CI] = 0.04-0.91, p = 0.03). Among 14 patients with final eTICI 3 scores, hypoperfusion was found in 1 of 7 (14%) in the alteplase group and 3 of 7 (43%) in the placebo group. Abnormal brain perfusion was associated with worse functional outcome at day 90. Alteplase significantly reduced the infarct expansion ratio compared with placebo (median [interquartile range (IQR)] = 0.7 [0.5-1.2] vs 3.2 [1.8-5.7], p = 0.01) and resulted in higher NAA peaks (median [IQR] = 1.13 [0.91-1.36] vs 1.00 [0.74-1.22], p < 0.0001). Interpretation: There is a high prevalence of areas of hypoperfusion following thrombectomy despite successful reperfusion on angiography. Adjunct alteplase enhances brain reperfusion, which results in reduced expansion of the infarction and improved neuronal integrity.

Incidence, severity and impact on functional outcome of persistent hypoperfusion despite large-vessel recanalization, a potential marker of impaired microvascular reperfusion: Systematic review of the clinical literature

“…Note that all studies save one 25 had as overall (explicit or implicit) assumption that the better the reperfusion after thrombectomy, the better the clinical outcome. Laredo et al 25 tested the hypothesis that intra-arterial thrombolysis administered after complete recanalization would prevent or dissolve microvascular thrombi/emboli.…”

“…Out of 15 initially identified articles that used any TICI scheme, 8 fulfilled the above stringent criteria. 20,22 –26,30,32,33 The remainder either used old TICI schemes, did not report the incidence of hypoperfusion separately for new-m/eTICI3 and TICI 2c, or did not respond to our repeated email invitation to provide such data. 21,27 –29,31,43,44…”

Uric Acid

“…50 Nonetheless, in a nested-perfusion MRI study performed post-MT, the prevalence of microvascular hypoperfusion (no-reflow phenomenon) was 58% in the placebo group and it was significantly reduced among patients treated with adjunctive thrombolysis. 51 These findings underscore the limitation of cerebral angiography in assessing the state of the microcirculation after MT. At the same time, they highlight the contribution of microcirculation to the clinical impact of thrombectomy, thus identifying an important new therapeutic target (Figure 2).…”

Endovascular Thrombectomy for Anterior Circulation Large Vessel Occlusion Stroke: An Evolution of Trials

“…59 60 It is unknown whether the no-reflow phenomenon leads to the development of further infarct or if it is a result of infarcted tissue. Zones of hypoperfusion in the CHOICE trial were verified by perfusion imaging 61 and were not recognized by conventional angiography. The trial was stopped early due to lack of placebo supply.…”