Contrast-enhanced sonothrombolysis in acute ischemic stroke patients without intracranial large-vessel occlusion

Contrast-enhanced sonothrombolysis (CEST) leads to a more rapid recanalization in acute ischemic stroke caused by intracranial large-vessel occlusion (LVO). Animal studies have shown that CEST also may be safe and efficient in treating the ischemic microcirculation in the absence of LVO. The exact mechanism behind this treatment effect is not known. We aimed to assess safety and efficacy of CEST in acute ischemic stroke patients included in the Norwegian Sonothrombolysis in Acute Stroke Study (NOR-SASS) without LVO on admission CT angiography (CTA).

NOR-SASS was a randomized controlled trial of CEST in ischemic stroke patients treated with intravenous thrombolysis within 4.5 hours after stroke onset. Patients were randomized to either CEST or sham CEST. In this study, patients were excluded if they had partial or total occlusion on admission CTA, ultrasound-resistant bone window, had received CEST with incorrect insonation as compared to stroke location on Magnetic resonance imaging (MRI), or were stroke mimics.

Of the 183 patients included in NOR-SASS, a total of 83 (45.4%) patients matched the inclusion criteria, of which 40 received CEST and 43 sham CEST. There were no patients with symptomatic intracranial hemorrhage (sICH) in the CEST group. Rates of asymptomatic ICH, microbleeds, and mortality were not increased in the CEST group. Neurological improvement at 24 hours and functional outcome at 90 days were similar in both groups.

CEST is safe in ischemic stroke patients without intracranial LVO. There were no differences in clinical outcomes between the treatment groups.