Impact of intravenous alteplase on sub-angiographic emboli in high-resolution diffusion-weighted imaging following successful thrombectomy

Abstract

Objective Thrombus microfragmentation causing peripheral emboli (PE) during mechanical thrombectomy (MT) may modulate treatment effects, even in cases with successful reperfusion. This study aims to investigate whether intravenous alteplase is of potential benefit in reducing PE after successful MT. Methods Patients from a prospective study treated at a tertiary care stroke center between 08/2017 and 12/2019 were analyzed. The main inclusion criterion was successful reperfusion after MT (defined as expanded thrombolysis in cerebral infarction (eTICI) scale ≥ 2b50) of large vessel occlusion anterior circulation stroke. All patients received a high-resolution diffusion-weighted imaging (DWI) follow-up 24 h after MT for PE detection. Patients were grouped as “direct MT” (no alteplase) or as MT plus additional intravenous alteplase. The number and volume of ischemic core lesions and PE were then quantified and analyzed. Results Fifty-six patients were prospectively enrolled. Additional intravenous alteplase was administered in 46.3% (26/56). There were no statistically significant differences of PE compared by groups of direct MT and additional intravenous alteplase administration regarding mean numbers (12.1, 95% CI 8.6–15.5 vs. 11.1, 95% CI 7.0–15.1; p = 0.701), and median volume (0.70 mL, IQR 0.21–1.55 vs. 0.39 mL, IQR 0.10–1.62; p = 0.554). In uni- and multivariable linear regression analysis, higher eTICI scores were significantly associated with reduced PE, while the administration of alteplase was neither associated with numbers nor volume of peripheral emboli. Additional alteplase did not alter reperfusion success. Conclusions Intravenous alteplase neither affects the number nor volume of sub-angiographic DWI-PE after successful endovascular reperfusion. In the light of currently running randomized trials, further studies are warranted to validate these findings. Key Points • Thrombus microfragmentation during endovascular stroke treatment may cause peripheral emboli that are only detectable on diffusion-weighted imaging and may directly compromise treatment effects. • In this prospective study, the application of intravenous alteplase did not influence the occurrence of peripheral emboli detected on high-resolution diffusion-weighted imaging. • A higher degree of recanalization was associated with a reduced number and volume of peripheral emboli and better functional outcome, while contrariwise, peripheral emboli did not modify the effect of recanalization on modified Rankin Scale scores at day 90.

Predictors of futile recanalization after endovascular treatment in acute ischemic stroke: a meta-analysis

“…The observation that pre-procedural IVT therapy is associated with a lower incidence of FR may be explained by the synergistic action of IVT and EVT in targeting small vessel recanalization and improving distal microvascular perfusion. But this hypothesis needs further investigation because evidence suggests that IVT did not influence the occurrence of EVT-induced peripheral emboli detected on high-resolution diffusion-weighted imaging 42. Meanwhile, the observed association may be confounded by the time from last seen well, since IVT is always given in an early time window.…”

Effect of Intravenous Alteplase on Functional Outcome and Secondary Injury Volumes in Stroke Patients with Complete Endovascular Recanalization

“…A further argument in favor of IVT was a supposedly improved microcirculation, and less peripheral emboli in new territories [ 39 ]. A recent study, however, observed that IVT had no effect on the number and volume of peripheral emboli after EVT independent of the degree of recanalization using high-resolution diffusion-weighted imaging [ 40 ].…”

MRI-Based Microthrombi Detection in Stroke with Polydopamine Iron Oxide

“…MT can be employed either in tandem with or as a potential alternative to rtPA-mediated thrombolysis, broadening the scope of AIS patient eligibility for treatment. However, microembolic signals are found in patients treated with thrombolytics 7,8 , and microfragmentations of the proximal thrombus -denoted as microthrombi -manifesting as distal microvascular migration are observed in 14 to 20% of patients undergoing MT 9 . The persistence of microthrombi despite a successful recanalisation of the occluded artery is associated with an increased risk of dementia and unfavorable patient outcomes [10][11][12] .…”