Taboos and opportunities in sonothrombolysis for stroke

Systemic thrombolysis with tissue plasminogen activator (tPA) is the only approved treatment for acute ischaemic stroke that improves functional outcome if given up to 4.5 h from symptom onset. At least half of treated patients have unfavourable outcomes long-term though, emphasising the need to amplify the only approved acute stroke therapy. Ultrasound targeting of an intra-arterial occlusive clot and delivering mechanical pressure to its surrounding fluids (referred to as sonothrombolysis) accelerates the thrombolytic effect of tPA. Higher recanalisation rates produce a trend towards better functional outcomes that could be safely achieved with the combination of 2 MHz frequency ultrasound and systemic tPA. To further accelerate the clot-dissolving effect of ultrasound, a variety of frequencies and intensities as well as other adjuvant treatment elements are being studied. However, literature reports argue efficacy and safety of these novel approaches doubting promptly translation into the clinical practice. This review will summarise our current knowledge about potentially harmful (taboos) directions and what we think are promising avenues for these future stroke therapies. We also give a prospect for novel technologies such as operator-independent devices that aim to further spread the use of sonothrombolysis for stroke.