Does the administration of sonothrombolysis along with tissue plasminogen activator improve outcomes in acute ischemic stroke? A systematic review and meta-analysis

This meta-analysis was conducted to assess the safety and efficacy of sonothrombolysis along with intravenous recombinant tissue plasminogen activator, alteplase (IV rtPA), in the management of acute ischemic stroke. Electronic databases were searched under different meSH terms without the restriction of time and language. 1415 studies were analyzed and seven studies that matched the inclusion criteria were selected. Multiple safety and efficacy outcomes were extracted. Our pooled analysis demonstrated that there is no significant difference between sonothrombolysis group and control group in preventing mortality (RR 1.10 [0.81, 1.50]; p = 0.55; I² = 0%) and intracranial hemorrhage (RR 1.11 [0.76, 1.63]; p = 0.59; i² = 0%), however, among the efficacy outcomes; complete recanalization after 60-120 min was achieved more effectively in the sonothrombolysis group (RR 2.11 [1.48, 3.03]; p ≤ 0.0001; I² = 0%). The rest of the efficacy outcomes like neurological improvement at 24 h (RR 1.20 [0.92, 1.57]; p = 0.18; I² = 40%) and excellent functional outcome after 3 months (RR 1.19 [0.93, 1.52]; p = 0.17; I² = 35%) showed no significant differences between the two groups. In subgroup analysis, we found that sonothrombolysis led to a better neurological improvement in patients who were less than 65 years of age (RR 1.20 [0.92, 1.57]; p = 0.05; I² = 40%). Moreover, there were no significant differences in the following of the subgroups assessed: (a) microsphere or microbubble use, (b) Ultrasound frequency (2 MHz or < 2 MHz), (c) transcranial Doppler (TCD) duration (1 h or 2 h), (d) age (≤ 65 or > 65).