Clinical experience and the published evidence all suggest that tPA is most effective for intracranial vessel occlusive disease when the drug is able to hit and penetrate the thrombus, whether it gets there through typical IV/IA measures, supported by ultrasound or mechanical thrombectomy. The particular concern with large proximal clots is that the tPA is delivered to the arterial dead-end and unable to work on the extensive thrombus. We know from our diagnostics, particularly transcranial Doppler and conventional angiography, that in the presence of what looks like a complete dead end on non-invasive angiography actually allows for minimal flow around the thrombus. However, this finding remains descriptive and of unknown clinical significance.


An international collaboration of stroke neurologists studied the use of a CT perfusion algorithm focused on contrast delay to quantify this very phenomenon and correlate it to vessel recanalization. The details of the sequence – not currently a mainstream clinical parameter – are in the manuscript but, on a very basic level, the CT study is of the time delay of contrast moving across a CTA-identified thrombus. Lower delay time to the distal end of a thrombus, and indicator of occult antegrade flow, predicted early recanalization as compared to those with longer delay time. In multivariate analysis, patients with occult antegrade flow and a delay of < 2s were 12 times more likely to have early recanalization (within 4 hours in this study) than those with a delay of > 2s.

These data have implications for clinical practice. The first application that comes to mind is that the detection of occult antegrade flow with a proximal occlusion may be a biomarker of the rare bird who responds favorably to IV tPA alone. This finding may also assist in the selection of multimodal clot extraction tools. Studies for another day!